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International Society of Cardiovascular Infectious Diseases Guidelines for the Diagnosis, Treatment and Prevention of Disseminated Mycobacterium chimaera Infection Following Cardiac Surgery with Cardiopulmonary Bypass
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Correspondence
- Corresponding author. Address: Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland. Tel.: +41 44 255 92 37.
Correspondence information about the author B. HasseAffiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Correspondence
- Corresponding author. Address: Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Raemistrasse 100, 8091 Zurich, Switzerland. Tel.: +41 44 255 92 37.
Affiliations
- Clinical Microbiology, Mater Misericordiae University Hospital, Dublin, Ireland
Affiliations
- Institute for Infectious Diseases, University of Bern, Bern, Switzerland
Affiliations
- Diagnostic Mycobacteriology Group, National and WHO Supranational Reference Center for Mycobacteria, Research Center, Borstel, Germany
Affiliations
- Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland
Affiliations
- Departments of Medicine, Health Research Methods, Evidence and Impact, and Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
Affiliations
- Department of Internal Medicine II, Division of Infectious Diseases, Medical Center - University of Freiburg, Freiburg i.Br, Germany
Affiliations
- Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain
Affiliations
- Kaiser Permanente Infectious Diseases, Los Angeles Medical Center, CA, USA
Affiliations
- Infectious and Tropical Diseases Department, San Bortolo Hospital, Vincenca, Italy
Affiliations
- Institute of Anesthesiology, University Hospital Zurich, Switzerland
Affiliations
- Department of Anaesthesiology, Kaiser Permanente, Los Angeles Medical Center, CA, USA
Affiliations
- Infectious and Transplant Medicine, University of Campania ‘L. Vanvitelli’, Monaldi Hospital, Naples, Italy
Affiliations
- Division of Infectious Diseases, Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China
Affiliations
- Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
Affiliations
- Department of Infectious Diseases, Cleveland Clinic, OH, USA
Affiliations
- Acute Communicable Disease Control, Los Angeles Department of Public Health, LA, USA
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Affiliations
- Molecular and Experimental Mycobacteriology Group, Research Center Borstel, Borstel, Germany and German Center for Infection Research (DZIF), partner site Hamburg - Lübeck - Borstel - Riems, Borstel, Germany
Affiliations
- Molecular and Experimental Mycobacteriology Group, Research Center Borstel, Borstel, Germany and German Center for Infection Research (DZIF), partner site Hamburg - Lübeck - Borstel - Riems, Borstel, Germany
Affiliations
- Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA
Affiliations
- Department of Infectious Diseases, The Alfred and Central Clinical School, Monash University, Melbourne, Australia
Affiliations
- Penn State Health, Milton S. Hershey Medical Center, Hershey, PA, USA
Affiliations
- Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, USA
Affiliations
- Healthcare-associated Infections, European Centre for Disease Prevention and Control (ECDC), Solna, Sweden
Affiliations
- National Infection Service, Public Health England, London, UK
Affiliations
- National Infection Service, Public Health England, London, UK
- Guy's and St Thomas' NHS Foundation Trust, Imperial College London, UK
Affiliations
- Centre for Cardiovascular Surgery and Transplantation, Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Affiliations
- National Center for Mycobacteria, Zurich, Switzerland, Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
Affiliations
- Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland
Affiliations
- Department of Infection and Tropical Medicine, University Hospitals Birmingham, Birmingham, UK
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Affiliations
- Department of Medical Microbiology, Radboud University Medical Center, Nijmegen, the Netherlands
Affiliations
- Clinic for Cardiovascular Surgery, University Hospital and University of Zurich, Switzerland
Affiliations
- Division of Infectious Diseases, University of Iowa, Carver College of Medicine, IA, USA
Affiliations
- Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA
Affiliations
- Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA
Affiliations
- Division of Infectious Diseases, Departments of Medicine and Cardiovascular Diseases, Mayo Clinic, College of Medicine and Science, Rochester, MN, USA
Affiliations
- Infectious Diseases Service at the Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
Affiliations
- Department of Infectious Diseases and Tropical Medicine, University Medical Center of Nancy, Vandoeuvre Cedex, France
Correspondence
- Corresponding author. Address: Department of Infectious Diseases and Tropical Medicine, University Medical Center of Nancy, Vandoeuvre Cedex. France.
Correspondence information about the author B. HoenAffiliations
- Department of Infectious Diseases and Tropical Medicine, University Medical Center of Nancy, Vandoeuvre Cedex, France
Correspondence
- Corresponding author. Address: Department of Infectious Diseases and Tropical Medicine, University Medical Center of Nancy, Vandoeuvre Cedex. France.
Affiliations
- Infectious Diseases Department at Barwon Health, University of Melbourne and Deakin University, Australia
Affiliations
- Geffen School of Medicine at UCLA Senior Investigator – LA Biomedical Research Institute at Harbor-UCLA, USA
Affiliations
- Department for Infectious Diseases, School of Medicine, University of Zagreb, Croatia
Affiliations
- Duke University Medical Center, Hubert-Yeargan Center for Global Health, Department of Medicine, Duke University Medical Center, Durham, NC, USA
Affiliations
- Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA
Affiliations
- Division of Infectious Diseases, Duke University Medical Center, Durham, NC, USA
Affiliations
- Division of Infectious Diseases, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
Affiliations
- Departments of Medicine and Molecular Genetics & Microbiology, Duke University Medical Center, Durham, NC, USA
Affiliations
- Department of Infectious Diseases and Tropical Medicine, University Medical Center of Nancy, Vandoeuvre Cedex, France
Affiliations
- Harvard Medical School, Division of Infectious Diseases at the Beth Israel Deaconess Medical Center, Boston, MA, USA
Affiliations
- Infectious and Transplant Medicine of the ‘V. Monaldi’ Teaching Hospital in Naples, University of Campania ‘L. Vanvitelli’, Italy
Affiliations
- Infectious Diseases at the Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
Affiliations
- Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, College of Medicine and Science, Rochester, MN, USA
Infectious Diseases SpecialistsAffiliations
- Division of Infectious Diseases, Departments of Medicine and Cardiovascular Medicine, Mayo Clinic, College of Medicine and Science, Rochester, MN, USA
Affiliations
- Division of Infectious Diseases, Departments of Medicine and Cardiovascular Medicine, Mayo Clinic, College of Medicine and Science, Rochester, MN, USA
Affiliations
- Division of Infectious Diseases, University of Iowa, Carver College of Medicine, Iowa, USA
Affiliations
- Division of Infectious Diseases, University of Iowa, Carver College of Medicine, Iowa, USA
Affiliations
- Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona Spain
Affiliations
- Servei de Malalties Infeccioses, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona Spain
Affiliations
- Department of Infectious Diseases, Cleveland Clinic, OH, USA
Affiliations
- Department of Infectious Diseases, Cleveland Clinic, OH, USA
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Affiliations
- Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
Affiliations
- Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark
Affiliations
- Infectious and Tropical Diseases Department, San Bortolo Hospital, Vincenza, Italy
Affiliations
- Infectious and Tropical Diseases Department, San Bortolo Hospital, Vincenza, Italy
Affiliations
- Department of Internal Medicine II, Division of Infectious Diseases, Medical Center, University of Freiburg, Freiburg i.Br, Germany
Affiliations
- Department of Internal Medicine II, Division of Infectious Diseases, Medical Center, University of Freiburg, Freiburg i.Br, Germany
Affiliations
- Division of Infectious Diseases, Department of Medicine, Queen Elizabeth Hospital, The University of Hong Kong, China
Affiliations
- Division of Infectious Diseases, Department of Medicine, Queen Elizabeth Hospital, The University of Hong Kong, China
Hospital EpidemiologistsAffiliations
- Departments of Medicine, Health Research Methods, Evidence and Impact, and Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
Affiliations
- Departments of Medicine, Health Research Methods, Evidence and Impact, and Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland
Affiliations
- Department of Infectious Diseases, Bern University Hospital, Bern, Switzerland
Affiliations
- Department of Infectious Diseases, Bern University Hospital, Bern, Switzerland
Affiliations
- Department of Infectious Diseases Monash University, Australia
Affiliations
- Department of Infectious Diseases Monash University, Australia
Affiliations
- Penn State Health, Milton S. Hershey Medical Center, Hershey, PA, USA
Affiliations
- Penn State Health, Milton S. Hershey Medical Center, Hershey, PA, USA
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Basel, Switzerland
Affiliations
- Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Basel, Switzerland
Microbiologists and Molecular Typing SpecialistsAffiliations
- Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA
Affiliations
- Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA
Affiliations
- Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA
Affiliations
- Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, CO, USA
Affiliations
- Centre for Cardiovascular Surgery and Transplantation, Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Affiliations
- Centre for Cardiovascular Surgery and Transplantation, Brno, Faculty of Medicine, Masaryk University, Brno, Czech Republic
Affiliations
- Department of Medical Microbiology, Radboud University Medical Centre, the Netherlands
Affiliations
- Department of Medical Microbiology, Radboud University Medical Centre, the Netherlands
Affiliations
- Institute of Medical Microbiology, University of Zurich, Switzerland and Institute for Infectious Diseases, University of Bern, Bern, Switzerland
Affiliations
- Institute of Medical Microbiology, University of Zurich, Switzerland and Institute for Infectious Diseases, University of Bern, Bern, Switzerland
Affiliations
- Molecular and Experimental Mycobacteriology Group, Reserch Center, Borstel Germany
Affiliations
- Molecular and Experimental Mycobacteriology Group, Reserch Center, Borstel Germany
Affiliations
- Diagnostic Mycobacteriology Group, National and WHO Supranational Reference Center for Mycobacteria, Research Center, Borstel Germany
Affiliations
- Diagnostic Mycobacteriology Group, National and WHO Supranational Reference Center for Mycobacteria, Research Center, Borstel Germany
Affiliations
- Molecular and Experimental Mycobacteriology Group, Research Center, Borstel Germany and German Center for Infection Research (DZIF), partner site Hamburg - Lübeck - Borstel - Riems, Borstel, Germany
Affiliations
- Molecular and Experimental Mycobacteriology Group, Research Center, Borstel Germany and German Center for Infection Research (DZIF), partner site Hamburg - Lübeck - Borstel - Riems, Borstel, Germany
Affiliations
- Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA
Affiliations
- Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, TX, USA
Cardiac Surgeons/ Perfusionists/ CardiologistsAffiliations
- Clinic for Cardiovascular Surgery, University Hospital of Zurich, Switzerland
Affiliations
- Clinic for Cardiovascular Surgery, University Hospital of Zurich, Switzerland
Ophthalmology
AnaesthesiologistsAffiliations
- Institute of Anaesthesiology, University Hospital Zurich, Switzerland
Affiliations
- Institute of Anaesthesiology, University Hospital Zurich, Switzerland
Affiliations
- Department of Anaesthesiology, Kaiser Permanente, Los Angeles Medical Center, LA, USA
Affiliations
- Department of Anaesthesiology, Kaiser Permanente, Los Angeles Medical Center, LA, USA
Public HealthAffiliations
- National Infection Service, Public Health England, Guy's and St Thomas' NHS Foundation Trust, Imperial College London, London, England, UK
Affiliations
- National Infection Service, Public Health England, Guy's and St Thomas' NHS Foundation Trust, Imperial College London, London, England, UK
Affiliations
- Acute Communicable Disease Control, Los Angeles Department of Public Health, LA, USA
Affiliations
- Acute Communicable Disease Control, Los Angeles Department of Public Health, LA, USA
Affiliations
- European Centre for Disease Prevention and Control (ECDC), Solna, Sweden
Affiliations
- European Centre for Disease Prevention and Control (ECDC), Solna, Sweden
Affiliations
- Acute Communicable Disease Control, Los Angeles Department of Public Health, LA, USA
Affiliations
- Acute Communicable Disease Control, Los Angeles Department of Public Health, LA, USA
Affiliations
- Centers for Disease Control and Prevention, Atlanta, GA, USA
Affiliations
- Centers for Disease Control and Prevention, Atlanta, GA, USA
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Figure 1
An algorithm for microbiological diagnosis of suspected cardiovascular infections including possible M. chimaera infections. IE, infective endocarditis; PCR, polymerase chain reaction; AFB, acid-fast bacilli; MALDI-TOF, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (adapted from [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31]). *Among patients meeting exposure criterion and a having a suggestive clinic consider upfront AFB cultures.
Article Outline
- Background
- Scope and aims
- Guidelines assembly and conflicts of interest
- Epidemiology and risk factors
- Multidisciplinary hospital patient management
- Diagnosis of M. chimaera infection
- Antimicrobial therapy
- Surgical intervention
- Follow-up and prognosis
- Considerations for patient notification, screening and investigation
- Prevention, infection control measures and reporting obligation
- Areas of future research
- Funding sources
- Conflict of interest statement
- Authors' contributions statement
- Appendix A.
- References
Summary
Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectious Diseases (ISCVID) covers aspects of prevention (field of hospital epidemiology), clinical management (infectious disease specialists, cardiac surgeons, ophthalmologists, others), laboratory diagnostics (microbiologists, molecular diagnostics), device management (perfusionists, cardiac surgeons) and public health aspects.
Keywords:
Mycobacterial, Mycobacterium chimaera, Cardiopulmonary bypass, Disseminated, Infection, Guidelines, ISCVID, Outbreaks, Heater-cooler deviceBackground
Mycobacterium chimaera is an environmental, slowly-growing non-tuberculous mycobacterium (NTM) [1x[1]Tortoli, E., Rindi, L., Garcia, M.J., Chiaradonna, P., Dei, R., Garzelli, C. et al. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov. Int J Syst Evol Microbiol. 2004;
54: 1277–1285
Google ScholarSee all References1] and, until recently, would have been identified by most clinical microbiology laboratories as M. intracellulare or M. avium complex (MAC). Prior to this current global outbreak, M. chimaera was recognized as a cause of respiratory and disseminated infections among immunocompromised patients [2x[2]Schweickert, B., Goldenberg, O., Richter, E., Gobel, U.B., Petrich, A., Buchholz, P. et al. Occurrence and clinical relevance of Mycobacterium chimaera sp. nov., Germany. Emerg Infect Dis. 2008;
14: 1443–1446
Google ScholarSee all References2]. Since 2013, a global outbreak of disseminated M. chimaera has been ongoing among patients who underwent open-chest surgery with cardiopulmonary bypass (CPB) [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References, 4x[4]Sax, H., Bloemberg, G., Hasse, B., Sommerstein, R., Kohler, P., Achermann, Y. et al. Prolonged outbreak of Mycobacterium chimaera infection after open-chest heart surgery. Clin Infect Dis. 2015;
61: 67–75
Google ScholarSee all References, 5x[5]Zweifel, S.A., Mihic-Probst, D., Curcio, C.A., Barthelmes, D., Thielken, A., Keller, P.M. et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Ophthalmology. 2017;
124: 178–188
Google ScholarSee all References, 6x[6]Kuehl, R., Banderet, F., Egli, A., Keller, P.M., Frei, R., Dobele, T. et al. Different types of heater–cooler units and their risk of transmission of Mycobacterium chimaera during open-heart surgery: clues from device design. Infect Control Hosp Epidemiol. 2018;
39: 834–840
Google ScholarSee all References, 7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References, 8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References, 9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References, 10x[10]Chiesi, S., Piacentini, D., Salerno, N.D., Luise, D., Peracchi, M., Concia, E. et al. Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature. Infez Med. 2017;
25: 267–269
Google ScholarSee all References, 11x[11]Cappabianca, G., Paparella, D., D’Onofrio, A., Caprili, L., Minniti, G., Lanzafame, M. et al. Mycobacterium chimaera infections following cardiac surgery in Italy: results from a National Survey Endorsed by the Italian Society of Cardiac Surgery. J Cardiovasc Med (Hagerstown). 2018;
19: 748–755
Google ScholarSee all References, 12x[12]Gasch, O., Meije, Y., Espasa, M., Font, B., Jimenez, S., and Fernandez-Hidalgo, N. Disseminated infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol (Engl Ed). 2019;
72: 502–503
Google ScholarSee all References, 13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References, 14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References, 15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References, 16x[16]Oda, G., Ryono, R., Lucero-Obusan, C., Schirmer, P., Shanawani, H., Jacobs, K. et al. Epidemiologic review of veterans health administration patients with isolation of nontuberculous mycobacteria after cardiopulmonary bypass procedures. Infect Control Hosp Epidemiol. 2017;
38: 1103–1106
Google ScholarSee all References, 17x[17]Rudikoff, A.G., Ganocy, T.K., Kansagra, K., Torres, F.A., Humphries, B.D., and Hernandez Conte, A. Thoracolumbar osteomyelitis secondary to systemic Mycobacterium chimaera infection status post aortic valve replacement. J Cardiothoracic Vasc Anesth. 2019;
33: 1704–1709
Google ScholarSee all References, 18x[18]Shafizadeh, N., Hale, G., Bhatnagar, J., Alshak, N.S., and Nomura, J. Mycobacterium chimaera hepatitis: a new disease entity. Am J Surg Pathol. 2019;
43: 244–250
Google ScholarSee all References, 19x[19]Balsam, L.B., Louie, E., Hill, F., Levine, J., and Phillips, M.S. Mycobacterium chimaera left ventricular assist device infections. J Card Surg. 2017;
32: 402–404
Google ScholarSee all References, 20x[20]Cai, Y., Landolfo, K., and Renew, J.R. Mycobacterium infection from a cardiopulmonary bypass heater–cooler unit in a patient with steroid-induced immunosuppression. Can J Anaesth. 2017;
64: 513–516
Google ScholarSee all References, 21x[21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. Ann Thorac Surg. 2017;
104 (e43–e5)
Google ScholarSee all References, 22x[22]O’Neil, C.R., Taylor, G., Smith, S., Joffe, A.M., Antonation, K., Shafran, S. et al. Mycobacterium chimaera infection after aortic valve replacement presenting with aortic dissection and pseudoaneurysm. Open Forum Infect Dis. 2018;
5: ofy018
Google ScholarSee all References, 23x[23]Stewardson, A.J., Stuart, R.L., Cheng, A.C., and Johnson, P.D. Mycobacterium chimaera and cardiac surgery. Med J Aust. 2017;
206: 132–135
Google ScholarSee all References, 24x[24]Overton, K., Mennon, V., Mothobi, N., Neild, B., Martinez, E., Masters, J. et al. Cluster of invasive Mycobacteria chimaera infections following cardiac surgery demonstrating novel clinical features and risks of aortic valve replacement. Intern Med J. 2018;
48: 1514–1520
Google ScholarSee all References, 25x[25]Zhang, X., Lin, J., Feng, Y., Wang, X., McNally, A., and Zong, Z. Identification of Mycobacterium chimaera in heater–cooler units in China. Sci Rep. 2018;
8: 7843
Google ScholarSee all References] with all cases linked to contamination of a specific brand (Stockert 3T, LivaNova, London, United Kingdom) of heater-cooler device (HCD) used in CPB [4x[4]Sax, H., Bloemberg, G., Hasse, B., Sommerstein, R., Kohler, P., Achermann, Y. et al. Prolonged outbreak of Mycobacterium chimaera infection after open-chest heart surgery. Clin Infect Dis. 2015;
61: 67–75
Google ScholarSee all References4,26x[26]Perkins, K.M., Lawsin, A., Hasan, N.A., Strong, M., Halpin, A.L., Rodger, R.R. et al. Notes from the field: Mycobacterium chimaera contamination of heater–cooler devices used in cardiac surgery – United States. Morb Mortal Wkly Rep. 2016;
65: 1117–1118
Google ScholarSee all References, 27x[27]Williamson, D., Howden, B., and Stinear, T. Mycobacterium chimaera spread from heating and cooling units in heart surgery. New Engl J Med. 2017;
376: 600–602
Google ScholarSee all References, 28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References]. CPB temporarily replaces cardiopulmonary function during surgery with maintenance of blood flow and oxygenation, thus the common term of ‘heart–lung machine’ for the CPB pump. HCDs circulate water through heat exchangers and warm or cool blood passing through the CPB and cardioplegia solution circuits. Extracorporeal circulation provides a bloodless field for surgery and maintains vital organ perfusion.
M. chimaera has caused disseminated infections following a variety of open-chest surgeries with CPB, including placement of prosthetic heart valves, prosthetic aortic grafts, and mechanical circulatory support devices [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7] with a proclivity for ocular involvement [5x[5]Zweifel, S.A., Mihic-Probst, D., Curcio, C.A., Barthelmes, D., Thielken, A., Keller, P.M. et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Ophthalmology. 2017;
124: 178–188
Google ScholarSee all References5,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15] and granulomatous inflammation in multiple organs in some cases that prompted an initial misdiagnosis of sarcoidosis [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References14,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,29x[29]Ganatra, S., Sharma, A., D’Agostino, R., Gage, T., and Kinnunen, P. Mycobacterium chimaera mimicking sarcoidosis. Methodist Debakey Cardiovasc J. 2018;
14: 301–302
Google ScholarSee all References29]. Infections following on-pump coronary artery bypass graft (CABG) have also been rarely reported [9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9,30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016;
21
Google ScholarSee all References30]. Because there are no international clinical practice guidelines that provide recommendations in the diagnosis, management, and prevention of disseminated M. chimaera infections that occur following CPB, a multinational collaboration was convened for the development of guidelines that are outlined in this document.
Scope and aims
In 2017, the International Society for Cardiovascular Infectious Diseases (ISCVID) recognized the importance of disseminated mycobacterial infections in patients following open-chest surgery with CPB and the growing need for international guidance on diagnosis, management and prevention of these infections. Accordingly, the primary aims of this document were to (i) provide an update on M. chimaera epidemiology and risk factors, (ii) develop guidelines for diagnosis and management in individual patients, and (iii) outline infection prevention and control recommendations. This clinical practice guideline was developed by expert consensus after review of available literature. An evidence-based scoring system that was used in the European Society of Cardiology guidelines on infective endocarditis [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31] was included in the novel recommendations designated herein (Table Ia, Table Ibb ).
| Classes of recommendation | Definition | Suggested wording to use |
|---|---|---|
| Class I | Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective | Is recommended/is indicated |
| Class II | Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure | |
| Class IIa | Weight of evidence/opinion is in favour of usefulness/efficacy | Should be considered |
| Class IIb | Usefulness/efficacy is less well established by evidence/opinion | May be considered |
| Class III | Evidence or general agreement that the given treatment or procedure is not useful/effective and in some cases may be harmful. | Is not recommended |
Adapted from reference [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31].
| Level of evidence A | Data derived from multiple, randomized clinical trials or meta-analyses |
| Level of evidence B | Data derived from a single randomized clinical trial or large non-randomized studies |
| Level of evidence C | Consensus of opinion of the experts and/or small studies, retrospective studies, registries |
Adapted from reference [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31].
Guidelines assembly and conflicts of interest
During the bi-annual ISCVID meeting in Dublin in 2017, an expert consensus group, including infectious diseases specialists, hospital epidemiologists, cardiologists, pathologists, radiologists, and cardiac surgeons, formed a taskforce to develop recommendations on diagnosis, treatment and prevention of cardiovascular infections due to M. chimaera. Members of this expert group were selected by the ISCVID council to represent a variety of professionals involved in the medical care of patients with cardiovascular infectious diseases. Moreover, global representatives participated in development of these recommendations. The participants included those with expertise in infection prevention and control, clinical patient management (infectious diseases specialists, cardiac surgeons, ophthalmologists, anaesthesiologists), mycobacteriology laboratory diagnostics (microbiologists with experience in mycobacteriology and molecular diagnostics), device management (perfusionists, infection control specialists), and public health. Participants declared if they had conflicts of interest which would require disclosure of financial or other interests that could constitute actual, potential, or apparent conflicts. The expert group completed a literature review of studies published since 2013, when the first two cases were published [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3]. We searched Medline through the PubMed.gov database using the terms Mycobacterium chimaera or M. chimaera with the MESH terms ‘treatment’, ‘cardiac’, ‘HCD’, ‘infection control’ as well as specific antimicrobials and classes of antimicrobials. Only English language articles were included because the panel members could not reliably review non-English language studies.
Epidemiology and risk factors
Epidemiology and risk factors for HCD-associated M. chimaera infection
The absolute risk of acquiring M. chimaera infection is much lower than the risk of other types of infections that complicate open-chest surgeries with CPB including deep sternal surgical site infections, hospital-acquired pneumonias or urinary tract infections, and vascular access device infections [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8,14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References14]. The estimated risk for M. chimaera infection in patients undergoing open-chest surgery necessitating CPB in Switzerland was 11 cases/14,045 patients with valve procedures, resulting in 0.78 cases/1000 procedures (95% CI 0.41–1.45) [32x[32]Sommerstein, R., Hasse, B., Marschall, J., Sax, H., Genoni, M., Schlegel, M. et al. Global health estimate of invasive Mycobacterium chimaera infections associated with heater–cooler devices in cardiac surgery. Emerg Infect Dis. 2018;
24: 576–578
Google ScholarSee all References32]. In the United Kingdom, 16 cases in 112,644 patients with open-chest procedures were initially identified, resulting in 0.14 cases/1000 procedures (95% CI 0.08–0.23) [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8]. In the United States, numerous hospital-specific prevalence rates range from 1/1000 to 1/10,000 [26x[26]Perkins, K.M., Lawsin, A., Hasan, N.A., Strong, M., Halpin, A.L., Rodger, R.R. et al. Notes from the field: Mycobacterium chimaera contamination of heater–cooler devices used in cardiac surgery – United States. Morb Mortal Wkly Rep. 2016;
65: 1117–1118
Google ScholarSee all References26]. Given the long incubation periods and observed change in risk [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8], these estimates are not directly comparable as they are dependent on the years of surgery included and time point at which the risk estimates were calculated.
Reported risk factors for M. chimaera infection pertain to the operative procedure (aortic surgery with highest risk) [9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9], length of exposure to a running HCD [14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References14], specific HCD brand [28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References28], year of manufacture of HCD [33x[33]Sommerstein, R., Schreiber, P.W., Diekema, D.J., Edmond, M.B., Hasse, B., Marschall, J. et al. Mycobacterium chimaera outbreak associated with heater–cooler devices: piecing the puzzle together. Infect Control Hosp Epidemiol. 2017;
38: 103–108
Google ScholarSee all References33], the applied HCD disinfection measures [34x[34]Garvey, M.I., Ashford, R., Bradley, C.W., Bradley, C.R., Martin, T.A., Walker, J. et al. Decontamination of heater–cooler units associated with contamination by atypical mycobacteria. J Hosp Infect. 2016;
93: 229–234
Google ScholarSee all References34], the distance and positioning of HCD in the operating room (OR) [4x[4]Sax, H., Bloemberg, G., Hasse, B., Sommerstein, R., Kohler, P., Achermann, Y. et al. Prolonged outbreak of Mycobacterium chimaera infection after open-chest heart surgery. Clin Infect Dis. 2015;
61: 67–75
Google ScholarSee all References4,33x[33]Sommerstein, R., Schreiber, P.W., Diekema, D.J., Edmond, M.B., Hasse, B., Marschall, J. et al. Mycobacterium chimaera outbreak associated with heater–cooler devices: piecing the puzzle together. Infect Control Hosp Epidemiol. 2017;
38: 103–108
Google ScholarSee all References33] and the OR ventilation system [35x[35]Sommerstein, R., Ruegg, C., Kohler, P., Bloemberg, G., Kuster, S.P., and Sax, H. Transmission of Mycobacterium chimaera from heater–cooler units during cardiac surgery despite an ultraclean air ventilation system. Emerg Infect Dis. 2016;
22: 1008–1013
Google ScholarSee all References35]. Generation of aerosols from contaminated water systems of operational HCDs may have reached the surgical site through airflow generated by its cooling fans [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8]. To date, all clinical cases related to open-chest surgery with CPB have been associated with the use of Stockert 3T-HCDs (subsequently denoted ‘3T-HCD’) [26x[26]Perkins, K.M., Lawsin, A., Hasan, N.A., Strong, M., Halpin, A.L., Rodger, R.R. et al. Notes from the field: Mycobacterium chimaera contamination of heater–cooler devices used in cardiac surgery – United States. Morb Mortal Wkly Rep. 2016;
65: 1117–1118
Google ScholarSee all References, 27x[27]Williamson, D., Howden, B., and Stinear, T. Mycobacterium chimaera spread from heating and cooling units in heart surgery. New Engl J Med. 2017;
376: 600–602
Google ScholarSee all References, 28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References,30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016;
21
Google ScholarSee all References30,36x[36]Centers for Disease Control and Prevention. Non-tuberculous mycobacterium (NTM) infections and heater–cooler devices interim practical guidance. CDC,
Atlanta; October 2015 (Available at:)http://www.cdc.gov/HAI/pdfs/outbreaks/CDC-Notice-Heater-Cooler-Units-final-clean.pdf. ([last accessed March 2016])
Google ScholarSee all References36,37x[37]Svensson, E., Jensen, E.T., Rasmussen, E.M., Folkvardsen, D.B., Norman, A., and Lillebaek, T. Mycobacterium chimaera in heater–cooler units in denmark related to isolates from the United States and United Kingdom. Emerg Infect Dis. 2017;
23
Google ScholarSee all References37], which have a market share of about 70%. M. chimaera has been cultured in hospital tap water [38x[38]Lande, L., Alexander, D.C., Wallace, R.J. Jr., Kwait, R., Iakhiaeva, E., Williams, M. et al. Mycobacterium avium in community and household water, suburban Philadelphia, Pennsylvania, USA, 2010–2012. Emerg Infect Dis. 2019;
25: 473–481
Google ScholarSee all References38] and from water of most types of HCDs, and extracorporeal membrane oxygenation (ECMOs) water tanks on the market [39x[39]Kuehl, R., Banderet, F., Egli, A., Keller, P.M., Frei, R., Dobele, T. et al. Different types of heater–cooler units and their risk of transmission of Mycobacterium chimaera during open-heart surgery: clues from device design. Infect Control Hosp Epidemiol. 2018;
39: 834–840
Google ScholarSee all References39,40x[40]Trudzinski, F.C., Schlotthauer, U., Kamp, A., Hennemann, K., Muellenbach, R.M., Reischl, U. et al. Clinical implications of Mycobacterium chimaera detection in thermoregulatory devices used for extracorporeal membrane oxygenation (ECMO), Germany, 2015 to 2016. Euro Surveill. 2016;
: 21
Google ScholarSee all References40]. However, available air sample culture results from HCDs other than 3T have been reported to be negative [28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References28,37x[37]Svensson, E., Jensen, E.T., Rasmussen, E.M., Folkvardsen, D.B., Norman, A., and Lillebaek, T. Mycobacterium chimaera in heater–cooler units in denmark related to isolates from the United States and United Kingdom. Emerg Infect Dis. 2017;
23
Google ScholarSee all References37]. According to a recent study [6x[6]Kuehl, R., Banderet, F., Egli, A., Keller, P.M., Frei, R., Dobele, T. et al. Different types of heater–cooler units and their risk of transmission of Mycobacterium chimaera during open-heart surgery: clues from device design. Infect Control Hosp Epidemiol. 2018;
39: 834–840
Google ScholarSee all References6], air flow direction, location of cooling ventilators, continuous cooling of the water tank at 4°C, and an electronic reminder of disinfection cycle are four relevant differences between the 3T-HCD and Maquet HCU30 and HCU40, which are HCD models, that may contribute to differential infection risk. No published data exist on the respective safety aspects of several other HCD brands and models. Changes in recommended disinfection procedures by LivaNova in September 2014 were not successful in eliminating the risk of M. chimaera contamination [41x[41]Schreiber, P.W., Kuster, S.P., Hasse, B., Bayard, C., Ruegg, C., Kohler, P. et al. Reemergence of Mycobacterium chimaera in heater–cooler units despite intensified cleaning and disinfection protocol. Emerg Infect Dis. 2016;
22: 1830–1833
Google ScholarSee all References41]. Therefore, LivaNova implemented a device modification with installation of an internal sealing and vacuum system on existing 3T-HCD devices in 2017 [42x[42]LivaNova implements 3T heater–cooler device modification. (Available at:)https://investor.livanova.com/static-files/9cf37b42-8164-4eff-9820-7504e5dc3c1f; 2018. ([last accessed March 2019])
Google ScholarSee all References42]. Safety data collected following this modification, however, have not been published.
HCDs may be positioned adjacent to the CBP pump, and the exhaust airflow from the HCD may be directed towards the operating field, thus contributing to the risk of M. chimaera infection. An OR assessment of 3T-HCD exhaust demonstrated a higher concentration of cumulative particles measured behind the 3T-HCD (near the exhaust fan) than at the surgical field over a 180 minute run-time [43x[43]Stuckey, M., Christensen, B., and Moulton-Meissner, H. Out of thin air: assessing dispersion of Mycobacterium chimaera in the operating room. in: Abstract presented at: 67th Annual Epidemic Intelligence Service Conference, Atlanta, GA. ; April 17th, 2018
Google ScholarSee all References43]. Using smoke testing, laminar flow ventilation was insufficient to prevent aerosols containing M. chimaera generated by the 3T-HCD and circulated by the HCD exhaust fan from dispersing towards the surgical field [35x[35]Sommerstein, R., Ruegg, C., Kohler, P., Bloemberg, G., Kuster, S.P., and Sax, H. Transmission of Mycobacterium chimaera from heater–cooler units during cardiac surgery despite an ultraclean air ventilation system. Emerg Infect Dis. 2016;
22: 1008–1013
Google ScholarSee all References35,44x[44]Walker, J.T., Lamagni, T., and Chand, M. Evidence that Mycobacterium chimaera aerosols penetrate laminar airflow and result in infections at the surgical field. Lancet Infect Dis. 2017;
17: 1019
Google ScholarSee all References44].
Interestingly, only one suspected pulmonary M. chimaera infection has been reported among exposed operating room personnel [45x[45]Rosero, C.I. and Shams, W.E. Mycobacterium chimaera infection masquerading as a lung mass in a healthcare worker. IDCases. 2019;
15: e00526
Google ScholarSee all References45]. Although factors responsible for this observation have not been defined, hypotheses include: (i) M. chimaera pulmonary disease will only affect those with pre-existing pulmonary diseases (e.g. bronchiectasis) or with increased susceptibility to mycobacterial disease; (ii) concentration of M. chimaera in the air of the OR may not be high enough to cause pulmonary infection, especially in persons without risk factors for developing disease; and (iii) surgical mask use in the OR may provide protection. Identification of other potential respiratory pathogens, including Legionella species, in HCD water circuits has previously been recognized as a potential threat to patients and theatre staff [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8].
Population at risk
Based on the evidence to date, the population at risk of disseminated M. chimaera infection includes all patients undergoing open-chest surgery with a 3T-HCD running during surgery, with the implantation of prostheses (e.g. prosthetic valves, vascular grafts, ventricular assist devices) increasing the risk. Notably, 3T-HCD have also been associated with NTM infections other than M. chimaera [46x[46]Baker, A.W., Lewis, S.S., Alexander, B.D., Chen, L.F., Wallace, R.J. Jr., Brown-Elliott, B.A. et al. Two-phase hospital-associated outbreak of Mycobacterium abscessus: investigation and mitigation. Clin Infect Dis. 2017;
64: 902–911
Google ScholarSee all References46]. Patients who underwent a cardiac procedure with ‘standby’ CPB and therefore a running ‘standby’ 3T-HCD have an unquantified risk. In contrast to pulmonary NTM disease, where NTM-containing aerosols lead to pulmonary infection in patients with significant underlying structural lung disease (especially in those with underlying bronchiectasis) or are immunocompromised [47x[47]Griffith, D.E., Aksamit, T., Brown-Elliott, B.A., Catanzaro, A., Daley, C., Gordin, F. et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Resp Crit Care Med. 2007;
175: 367–416
Google ScholarSee all References47], the transmission route of HCD-related M. chimaera infection is non-inhalational and infection can occur in patients without previously known immune deficiency. The likely route of transmission for these non-pulmonary M. chimaera infections is direct contamination of the open-chest cavity with M. chimaera-containing aerosols during cardiac surgery. Although the majority of infections have followed open-chest cardiac surgery, infections have also been reported among patients following minimally-invasive cardiac surgery [21x[21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. Ann Thorac Surg. 2017;
104 (e43–e5)
Google ScholarSee all References21]. The hypothesized route of exposure among the latter is contamination of surgical equipment or grafts in the OR by 3T-HCD-generated bio-aerosols prior to use or implantation during surgery. These infections may involve the heart, due to valve/graft replacements, and may widely disseminate to involve a panoply of body-sites including kidney, liver, bone marrow, bone, vertebra, skin, brain and choroid. Cardiac conditions at risk of M. chimaera infections are listed in Table IITable II.
| Procedure | Class | Level |
|---|---|---|
Cardiopulmonary bypass surgery involving a 3T-HCD and one or more of the following:
| IIa | C |
Google ScholarSee all References14].
Google ScholarSee all References9,30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016; 21
Google ScholarSee all References30].
Multidisciplinary hospital patient management
Recommendations
- •
Management of M. chimaera-infected patients by an ‘Endocarditis Team’ is recommended (Class I, Level C).
The Task Force strongly supports management of M. chimaera-infected patients by a multidisciplinary ‘Endocarditis Team’ [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31]. Typically, initial M. chimaera infection symptoms are non-specific and often depend on the first body-site or organ involved, the surgical procedure performed, the underlying cardiac disease, and the baseline immunological status of the patient. Hence, the patient may present initially to a variety of medical specialties. Once infection is diagnosed, expertise from various medical specialties is needed including infectious diseases physicians, infection prevention and control practitioners, microbiologists, cardiologists, cardiac surgeons, ophthalmologists, internal medicine specialists, pharmacists as well as other specialties. Consultation with cardiac imaging specialists is recommended, as echocardiography and nuclear imaging with positron emission tomography (PET)/computed tomography (CT) are often critical in the diagnosis of infection, determining the extent of dissemination, and follow-up after treatment. Due to the complexity of antibiotic therapy, potential adverse drug effects and drug-drug interactions, anti-mycobacterial treatment should be guided by an infectious disease physician in close collaboration with a laboratory microbiologist with expertise in mycobacteriology as well as a clinical pharmacist. Despite the high perioperative risk with resection/excisional surgery, the outcome of patients with disseminated implant-associated infections may be improved when infected prosthetic material is removed [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9]. Serial discussions with the surgical team and the anesthesiologist are warranted to determine optimal timing of surgery once a surgical indication is recognized.
Diagnosis of M. chimaera infection
Clinical features
The diagnosis of cardiac M. chimaera infection can be difficult as initial symptoms may be non-specific, subtle and appear months to years after surgery [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8,14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References14,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15]. Extrathoracic symptoms may precede cardiac or vascular manifestations [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,10x[10]Chiesi, S., Piacentini, D., Salerno, N.D., Luise, D., Peracchi, M., Concia, E. et al. Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature. Infez Med. 2017;
25: 267–269
Google ScholarSee all References10,48x[48]Hasse, B. SY0821. Clinical management of Mycobacterium chimaera infection. ECCMID,
Austria; 2017 (Available at:)https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=44559. ([last accessed October 2019])
Google ScholarSee all References48] and signs of cardiac infection may be absent and detected only at surgery or post-mortem examination [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,10x[10]Chiesi, S., Piacentini, D., Salerno, N.D., Luise, D., Peracchi, M., Concia, E. et al. Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature. Infez Med. 2017;
25: 267–269
Google ScholarSee all References10,49x[49]Asadi, T., Mullin, K., Roselli, E., Johnston, D., Tan, C.D., Rodriguez, E.R. et al. Disseminated Mycobacterium chimaera infection associated with heater–cooler units after aortic valve surgery without endocarditis. J Thoracic Cardiovasc Surg. 2018;
155: 2369–2374
Google ScholarSee all References49]. Symptom development occurs, on average, 15–17 months post-surgery, but the incubation period can range from 6 weeks to more than 5 years [9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9,12x[12]Gasch, O., Meije, Y., Espasa, M., Font, B., Jimenez, S., and Fernandez-Hidalgo, N. Disseminated infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol (Engl Ed). 2019;
72: 502–503
Google ScholarSee all References12,50x[50]Schreiber, P.W., Hasse, B., and Sax, H. Mycobacterium chimaera infections after cardiac surgery – lessons learned. Clin Microbiol Infect. 2018;
24: 1117–1118
Google ScholarSee all References50]. Due, in part, to the long incubation period, clinician suspicion of disseminated M. chimaera infection is often low at initial presentation [13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13]. Non-specific and indolent symptoms often prompt alternative diagnoses [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References14,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15]. It is not unusual for affected patients to consult with a variety of specialists before a correct diagnosis is made. Common reported symptoms are prolonged fever, weight loss, generalized malaise and night sweats, with the addition of failure-to-thrive in infants [13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13]. The physical examination is frequently normal, but in some patients (new onset) heart murmur, signs of embolic complications or hepatosplenomegaly, local signs of sternal surgical site infection, or chorioretinitis are noted.
Cardiovascular diagnoses include prosthetic valve endocarditis [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References, 8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References, 9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References, 10x[10]Chiesi, S., Piacentini, D., Salerno, N.D., Luise, D., Peracchi, M., Concia, E. et al. Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature. Infez Med. 2017;
25: 267–269
Google ScholarSee all References,13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13,20x[20]Cai, Y., Landolfo, K., and Renew, J.R. Mycobacterium infection from a cardiopulmonary bypass heater–cooler unit in a patient with steroid-induced immunosuppression. Can J Anaesth. 2017;
64: 513–516
Google ScholarSee all References20,21x[21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. Ann Thorac Surg. 2017;
104 (e43–e5)
Google ScholarSee all References21,30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016;
21
Google ScholarSee all References30], aortic graft infections [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9,13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,49x[49]Asadi, T., Mullin, K., Roselli, E., Johnston, D., Tan, C.D., Rodriguez, E.R. et al. Disseminated Mycobacterium chimaera infection associated with heater–cooler units after aortic valve surgery without endocarditis. J Thoracic Cardiovasc Surg. 2018;
155: 2369–2374
Google ScholarSee all References49], myocarditis [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3], infected pseudoaneurysms [22x[22]O’Neil, C.R., Taylor, G., Smith, S., Joffe, A.M., Antonation, K., Shafran, S. et al. Mycobacterium chimaera infection after aortic valve replacement presenting with aortic dissection and pseudoaneurysm. Open Forum Infect Dis. 2018;
5: ofy018
Google ScholarSee all References22], and cardiovascular implantable electronic device infections [12x[12]Gasch, O., Meije, Y., Espasa, M., Font, B., Jimenez, S., and Fernandez-Hidalgo, N. Disseminated infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol (Engl Ed). 2019;
72: 502–503
Google ScholarSee all References12] or mechanical circulatory support device infections [19x[19]Balsam, L.B., Louie, E., Hill, F., Levine, J., and Phillips, M.S. Mycobacterium chimaera left ventricular assist device infections. J Card Surg. 2017;
32: 402–404
Google ScholarSee all References19]. Infections following on-pump CABG procedures [30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016;
21
Google ScholarSee all References30] and infections after minimally invasive mitral valve procedures have been rarely reported [21x[21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. Ann Thorac Surg. 2017;
104 (e43–e5)
Google ScholarSee all References21]. Patients with cardiovascular infection due to M. chimaera may present with chest pain or signs of sternal surgical site infections [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8,13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13,14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References14] or mediastinitis [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8,16x[16]Oda, G., Ryono, R., Lucero-Obusan, C., Schirmer, P., Shanawani, H., Jacobs, K. et al. Epidemiologic review of veterans health administration patients with isolation of nontuberculous mycobacteria after cardiopulmonary bypass procedures. Infect Control Hosp Epidemiol. 2017;
38: 1103–1106
Google ScholarSee all References16]. Disseminated (extrathoracic) manifestations with bacteraemia may involve a variety of organs, including the lung, spleen, bone marrow, kidney, liver, brain, skin and bone [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8,10x[10]Chiesi, S., Piacentini, D., Salerno, N.D., Luise, D., Peracchi, M., Concia, E. et al. Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature. Infez Med. 2017;
25: 267–269
Google ScholarSee all References10,13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References, 14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References, 15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References,20x[20]Cai, Y., Landolfo, K., and Renew, J.R. Mycobacterium infection from a cardiopulmonary bypass heater–cooler unit in a patient with steroid-induced immunosuppression. Can J Anaesth. 2017;
64: 513–516
Google ScholarSee all References20,21x[21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. Ann Thorac Surg. 2017;
104 (e43–e5)
Google ScholarSee all References21,49x[49]Asadi, T., Mullin, K., Roselli, E., Johnston, D., Tan, C.D., Rodriguez, E.R. et al. Disseminated Mycobacterium chimaera infection associated with heater–cooler units after aortic valve surgery without endocarditis. J Thoracic Cardiovasc Surg. 2018;
155: 2369–2374
Google ScholarSee all References49]. Disseminated M. chimaera infections also have a proclivity for ocular [5x[5]Zweifel, S.A., Mihic-Probst, D., Curcio, C.A., Barthelmes, D., Thielken, A., Keller, P.M. et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Ophthalmology. 2017;
124: 178–188
Google ScholarSee all References5,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15] and central nervous system involvement [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7]. Atypical presentations are common [12x[12]Gasch, O., Meije, Y., Espasa, M., Font, B., Jimenez, S., and Fernandez-Hidalgo, N. Disseminated infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol (Engl Ed). 2019;
72: 502–503
Google ScholarSee all References, 13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References, 14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References,22x[22]O’Neil, C.R., Taylor, G., Smith, S., Joffe, A.M., Antonation, K., Shafran, S. et al. Mycobacterium chimaera infection after aortic valve replacement presenting with aortic dissection and pseudoaneurysm. Open Forum Infect Dis. 2018;
5: ofy018
Google ScholarSee all References22,30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016;
21
Google ScholarSee all References30] and a high index of suspicion is needed to avoid delays in diagnosis. In some cases, a diagnosis of presumptive sarcoidosis has been made [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13,48x[48]Hasse, B. SY0821. Clinical management of Mycobacterium chimaera infection. ECCMID,
Austria; 2017 (Available at:)https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=44559. ([last accessed October 2019])
Google ScholarSee all References48] based on granulomatous tissue formation leading to inappropriate immunosuppressive treatment.
Many patients present with evidence of disseminated disease that can include hepatic involvement (elevated transaminases and/or alkaline phosphatase) [18x[18]Shafizadeh, N., Hale, G., Bhatnagar, J., Alshak, N.S., and Nomura, J. Mycobacterium chimaera hepatitis: a new disease entity. Am J Surg Pathol. 2019;
43: 244–250
Google ScholarSee all References18], nephritis (impaired renal function), pneumonitis (impaired diffusion capacity on whole body plethysmography) [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3], bone marrow involvement with cytopenias (anaemia, leukocytopenia, and/or thrombocytopenia [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15]) or haemophagocytic syndrome [12x[12]Gasch, O., Meije, Y., Espasa, M., Font, B., Jimenez, S., and Fernandez-Hidalgo, N. Disseminated infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol (Engl Ed). 2019;
72: 502–503
Google ScholarSee all References12], spine involvement with spondylitis and spondylodiscitis [30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016;
21
Google ScholarSee all References30], arthritis [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7], or splenomegaly. A consistent histopathologic finding upon biopsy of involved body sites is the presence of non-caseating granulomas, often with negative AFB smears. Some patients also develop neurological complications with vasculitis of the brain, encephalitis or chorioretinitis [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,51x[51]Lau, D., Cooper, R., Chen, J., Sim, V.L., McCombe, J.A., Tyrrell, G.J. et al. Mycobacterium chimaera encephalitis post-cardiac surgery: a new syndrome. Clin Infect Dis. 2019 Jun 18;
([Epub ahead of print])
Google ScholarSee all References51].
Chorioretinitis
Chorioretinal lesions may be present in patients presenting with disseminated M. chimaera infection [5x[5]Zweifel, S.A., Mihic-Probst, D., Curcio, C.A., Barthelmes, D., Thielken, A., Keller, P.M. et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Ophthalmology. 2017;
124: 178–188
Google ScholarSee all References5,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,52x[52]Boni, C., Al-Sheikh, M., Hasse, B., Eberhard, R., Kohler, P., Hasler, P. et al. Multimodal imaging of choroidal lesions in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Retina. 2019;
39: 452–464
Google ScholarSee all References52]. The patients present with bilateral white-yellowish chorioretinal lesions varying from a few lesions to widespread miliary disease, and a subset of patients have had additional signs of mild anterior uveitis, intermediate uveitis or optic disc swelling [5x[5]Zweifel, S.A., Mihic-Probst, D., Curcio, C.A., Barthelmes, D., Thielken, A., Keller, P.M. et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Ophthalmology. 2017;
124: 178–188
Google ScholarSee all References5,52x[52]Boni, C., Al-Sheikh, M., Hasse, B., Eberhard, R., Kohler, P., Hasler, P. et al. Multimodal imaging of choroidal lesions in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Retina. 2019;
39: 452–464
Google ScholarSee all References52]. Depending on the location of the lesions and the presence of complications like choroidal neovascularization, these patients might not report visual complaints.
Choroidal manifestations in patients with disseminated M. chimaera infection are an important clue to this disease. A classification of choroidal lesions based on multimodal imaging is detailed in Table IIITable III, and a recommendation for screening and follow-up ophthalmological examinations in patients with suspected or confirmed M. chimaera infection is included in Table IVTable IV.
| Imaging modality | Active lesion | Inactive lesion Lesion in regression |
|---|---|---|
| Fundus photography | ||
| Shape | Ovoid to round | Ovoid to round |
| Border | Indistinct | Well-defined |
| Size | Small (<1 disc diameter) | Small (<1 disc diameter) |
| Colour | Yellow-white | Whitisha |
| Fluorescein angiography | ||
| Early | Hypofluorescent | Hyperfluorescent |
| Late | Hyperfluorescent | Hyperfluorescent |
| Indocyanine green angiography | Hypofluorescent | Hypofluorescent |
| Fundus autofluorescence | Hyperautofluorescent | Hypoautofluorescent |
| EDI-OCT | ||
| Shape | Full-thickness, round, well-defined borders | Poorly defined margins |
| Internal reflectivity | Hyporeflective | Similar to the choroid |
| Transmission effect | Increased | Increased |
EDI-OCT, spectral-domain optical coherence tomography including enhanced depth imaging.
| Timepoint | Imaging modalities | Class | Level |
|---|---|---|---|
| Baseline ocular examination | Complete ophthalmic examination Visual acuity Intraocular pressure measurement Anterior and posterior segment slit-lamp examination including dilated fundus biomicroscopy Multi-modal imaging testing Wide-angle fundus photography FA/ICGA (if possible, by using a wide-angle camera) FAF EDI-OCT OCTA (if available) | IIa | C |
| Follow-up ocular examinations | |||
| Absence of active ocular disease or Discontinuation of mycobacterial therapy | Clinical follow-up visits every 2 months with dilated fundusa Multi-modal imaging tests every 4 monthsa | IIb | C |
| Presence of active ocular disease | Clinical follow-up visits every month with dilated fundus examination Multi-modal imaging tests every 2 months | IIb | C |
EDI-OCT, spectral-domain optical coherence tomography including enhanced depth imaging; FAF, fundus autofluorescence imaging; FA/ICGA, fluorescein angiography/indocyanine green (ICG) angiography; OCTA, optical coherence tomography angiography.
Immune reconstitution inflammatory response syndrome
An immune reconstitution inflammatory syndrome (IRIS) can complicate tuberculosis treatment with a variety of clinical tuberculosis manifestations, with HIV-infection being an important risk factor [53x[53]Brown, C.S., Smith, C.J., Breen, R.A., Ormerod, L.P., Mittal, R., Fisk, M. et al. Determinants of treatment-related paradoxical reactions during anti-tuberculosis therapy: a case control study. BMC Infect Dis. 2016;
16: 479
Google ScholarSee all References53]. Nontuberculous mycobacteria usually cause IRIS only in HIV-infected patients [54x[54]Phillips, P., Bonner, S., Gataric, N., Bai, T., Wilcox, P., Hogg, R. et al. Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow-up. Clin Infect Dis. 2005;
41: 1483–1497
Google ScholarSee all References54]. In case of disseminated M. chimaera infection, several manifestations occurring after initiation of treatment have represented an IRIS including fever, abscess formations in various body sites (lymph nodes, ovary, spleen, prostate and bone), pancytopenia or chorioretinitis [48x[48]Hasse, B. SY0821. Clinical management of Mycobacterium chimaera infection. ECCMID,
Austria; 2017 (Available at:)https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=44559. ([last accessed October 2019])
Google ScholarSee all References48]. Patients have typically been treated with corticosteroids (1 mg/kg per body weight) as an adjunct to anti-mycobacterial therapy. Currently, the long-term outcome and the spectrum of disease of potential M. chimaera-related IRIS are yet to be fully defined.
Imaging techniques
Recommendations
- •
Transoesophageal echocardiogram for detection of cardiac vegetations, aortic root collections, and evaluation of valvular function is recommended (Class I, Level C).
- •
PET/CT imaging in case of suspected aortic graft infection or fever of unknown origin (FUO) should be considered (Class IIa, Level C).
In cases of suspected M. chimaera infection, echocardiography is central in the diagnosis, surgical assessment and post-operative follow-up [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7]. Vegetations, aortic root abscess, valve dysfunction including regurgitation and paravalvular or periprosthetic complications can be identified. Transthoracic echocardiography (TTE) should be performed as part of an initial assessment. However, as most cases have been associated with the presence of prosthetic material, additional transoesophageal echocardiography (TOE) is recommended, because of the increased sensitivity of TOE as compared to that of TTE. If extrathoracic infections precede cardiac manifestations, initial echocardiography may be normal [10x[10]Chiesi, S., Piacentini, D., Salerno, N.D., Luise, D., Peracchi, M., Concia, E. et al. Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature. Infez Med. 2017;
25: 267–269
Google ScholarSee all References10,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,20x[20]Cai, Y., Landolfo, K., and Renew, J.R. Mycobacterium infection from a cardiopulmonary bypass heater–cooler unit in a patient with steroid-induced immunosuppression. Can J Anaesth. 2017;
64: 513–516
Google ScholarSee all References20,21x[21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. Ann Thorac Surg. 2017;
104 (e43–e5)
Google ScholarSee all References21]. Therefore, repeat TOEs may be needed, especially among patients who do not respond well to antimicrobial treatment. For patients with prosthetic valve endocarditis and aortic graft infections, other imaging techniques such as 18F-fluorodeoxy-glucose PET with CT or cardiac contrast-enhanced CT are recommended [15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,55x[55]Wilson, W.R., Bower, T.C., Creager, M.A., Amin-Hanjani, S., O’Gara, P.T., Lockhart, P.B. et al. Vascular graft infections, mycotic aneurysms, and endovascular infections: a scientific statement from the American Heart Association. Circulation. 2016;
134 (e412–e60)
Google ScholarSee all References55,56x[56]Sah, B.R., Husmann, L., Mayer, D., Scherrer, A., Rancic, Z., Puippe, G. et al. Diagnostic performance of 18F-FDG-PET/CT in vascular graft infections. Eur J Vasc Endovasc Surg. 2015;
49: 455–464
Google ScholarSee all References56]. PET/CT, for example, can detect cardiovascular involvement and extracardiac complications when TOE is negative [15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,21x[21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. Ann Thorac Surg. 2017;
104 (e43–e5)
Google ScholarSee all References21,56x[56]Sah, B.R., Husmann, L., Mayer, D., Scherrer, A., Rancic, Z., Puippe, G. et al. Diagnostic performance of 18F-FDG-PET/CT in vascular graft infections. Eur J Vasc Endovasc Surg. 2015;
49: 455–464
Google ScholarSee all References, 57x[57]Roque, A., Pizzi, M.N., Cuellar-Calabria, H., and Aguade-Bruix, S. (18)F-FDG-PET/CT angiography for the diagnosis of infective endocarditis. Curr Cardiol Rep. 2017;
19: 15
Google ScholarSee all References, 58x[58]Granados, U., Fuster, D., Pericas, J.M., Llopis, J.L., Ninot, S., Quintana, E. et al. Diagnostic accuracy of 18F-FDG PET/CT in infective endocarditis and implantable cardiac electronic device infection: a cross-sectional study. J Nucl Med. 2016;
57: 1726–1732
Google ScholarSee all References, 59x[59]Orvin, K., Goldberg, E., Bernstine, H., Groshar, D., Sagie, A., Kornowski, R. et al. The role of FDG-PET/CT imaging in early detection of extra-cardiac complications of infective endocarditis. Clin Microbiol Infect. 2015;
21: 69–76
Google ScholarSee all References, 60x[60]Husmann, L., Huellner, M.W., Ledergerber, B., Anagnostopoulos, A., Stolzmann, P., Sah, B.R. et al. Comparing diagnostic accuracy of 18F-FDG-PET/CT, contrast enhanced CT and combined imaging in patients with suspected vascular graft infections. Eur J Nucl Med Mol Imaging. 2019;
46: 1359–1368
Google ScholarSee all References], and PET/CT is helpful in treatment monitoring [61x[61]Husmann, L., Ledergerber, B., Anagnostopoulos, A., Stolzmann, P., Sah, B.R., Burger, I.A. et al. The role of FDG PET/CT in therapy control of aortic graft infection. Eur J Nucl Med Mol Imaging. 2018;
45: 1987–1997
Google ScholarSee all References61].
Microbiological diagnosis
Laboratory culture methods
Mycobacteria only grow in and on specific media, thus a high index of suspicion on the side of the clinician is important and correct culture material (e.g. heparin or sodium citrate blood sent for mycobacterial cultures) needs to be used. A positive acid-fast bacilli (AFB) culture for mycobacteria from a specimen taken from a sterile extra-pulmonary site (blood, purulent material, bone marrow, tissue, or implanted prosthetic material) should be considered a suspect case. If there is no mycobacterial growth after 8 weeks of incubation, the culture is considered negative. Following growth, species identification and antimicrobial susceptibility testing (AST) are necessary to inform treatment. Laboratory culture methods are listed in Table VTable V. For all purulent materials and tissue samples, a combination of solid media (Middlebrook 7H10 or 7H11 or Lowenstein-Jensen) and mycobacterial growth indicator tubes (MGIT; BD, Franklin Lakes, NJ, USA) or other liquid systems such as VersaTrek (Thermofisher, Cleveland, OH, USA) should be used to maximize sensitivity [62x[62]van Ingen, J. Microbiological diagnosis of nontuberculous mycobacterial pulmonary disease. Clin Chest Med. 2015;
36: 43–54
Google ScholarSee all References62]. Of note, according to a recent case series of 30 patients with M. chimaera in the UK [9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9], the overall diagnostic sensitivity of one single mycobacterial blood culture is estimated to be 68% with multiple blood or urine cultures increasing the diagnostic yield. An even higher index of suspicion is needed to repeat blood cultures specifically for mycobacteria when initial cultures have not produced growth or if a bacterial PVE is already diagnosed [63x[63]Inojosa, W.O., Minniti, G., and Scotton, P.G. Is Mycobacterium chimaera infection after cardiac surgery a risk factor for bacterial prosthetic valve endocarditis?. Clin Infect Dis. 2019 Jun 20;
([Epub ahead of print])
Google ScholarSee all References63].
| Exposure assessment | History of surgery requiring cardiopulmonary bypass surgery prior to symptoms of infection |
|---|---|
| Laboratory assessment | |
| Culturea,b | M. chimaera positive cultures obtained from a sterile site (blood, purulent material, tissue biopsy, or implanted prosthetic material). Mycobacterial blood cultures (BacTec myco Lytic/F bottles BD Bioscience); VersaTrek (Thermofisher, formerly Trek Diagnostics, Cleveland, OH) use of Isolator tubes (Isolator 10, Oxoid; Isostatw System, WampoleTM) can either be directly inoculated at the point-of-care if the laboratory is on site or alternatively citrate/heparin blood should be sent to a mycobacteriology laboratory in case blood culture bottles are not available. |
| PCRc | Mycobacterium genus-specific PCR obtained from an invasive sample (blood, purulent material, tissue biopsy, or implanted prosthetic material). |
| Clinical assessmentd | |
| Cardiovascular manifestations | Prosthetic valve endocarditis |
| Prosthetic vascular graft infection | |
| Myocarditis | |
| Pseudoaneurysm formation | |
| Localized infections | Sternotomy wound infection |
| Mediastinitis | |
| Extrathoracic manifestationse | Bloodstream infection and disseminated infection including embolic and immunologic manifestations |
| Splenomegaly | |
| Bone marrow involvement with cytopenia | |
| Bone infection (arthritis, osteomyelitis) | |
| Pneumonitis | |
| Hepatitis | |
| Nephritis Skin infection | |
| Chorioretinitis | |
| Cerebral vasculitis | |
| Constitutional symptoms | |
| Fever | |
| Fatigue Weight loss Night sweats Joint pain Shortness of breath | |
| Infants: Failure to thrive/febrile episodes | |
| Histopathologyf | |
| Detection of non-caseating granuloma and foamy/swollen macrophages with/without acid-fast bacilli in cardiac tissue in the proximity of the prosthetic material | |
Confirmed cases: meet clinical and exposure criteria AND M. chimaera is detected by culture and polymerase chain reaction (PCR) identification from invasive sample (blood, purulent material, biopsy or prosthetic material).
Probable cases: meet clinical and exposure criteria AND M. chimaera is detected by PCR not by culture from invasive sample (blood, purulent material, biopsy or prosthetic material) operating theatre OR M. avium complex (MAC) is detected by culture and PCR identification from invasive sample (blood, purulent material, biopsy or prosthetic material) OR detection of non-caseating granuloma and foamy/swollen macrophages with acid-fast bacilli in cardiac tissue in the proximity of the prosthetic material or in specimen from sternotomy wound.
Google ScholarSee all References28]. If a laboratory confirms the organism's identity is consistent with the outbreak strain, it is recommended that healthcare authorities be informed.
Google ScholarSee all References15].
HCD water samples, if performed, should be cultured as recommended by the European Centre for Disease Prevention and Control (ECDC) [64x[64]European Centre for Disease Prevention and Control. Protocol for case detection, laboratory diagnosis and environmental testing of Mycobacterium chimaera infections potentially associated with heater–cooler units. (Available at:)http://ecdc.europa.eu/en/activities/diseaseprogrammes/ARHAI/Pages/about_programme.aspxEU. ([last accessed October 2019])
Google ScholarSee all References64]. However, the majority of isolates from HCDs contained mixed populations of two or more strains which led to potential mismatches between environmental and patient cultures in one survey [28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References28].
Molecular diagnosis
Most laboratory methods identify an M. chimaera isolate as a member of the M. avium complex (MAC) and not all laboratories are able to differentiate M. chimaera and M. intracellulare. The complete 16S rDNA gene sequences of MAC species differ by only 6–10 base pairs, and only one base pair discriminates M. chimaera and M. intracellulare [1x[1]Tortoli, E., Rindi, L., Garcia, M.J., Chiaradonna, P., Dei, R., Garzelli, C. et al. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov. Int J Syst Evol Microbiol. 2004;
54: 1277–1285
Google ScholarSee all References1]. Therefore, sequencing of the 16S–23S internal transcribed spacer region (ITS) has been suggested [65x[65]Wallace, R.J. Jr., Iakhiaeva, E., Williams, M.D., Brown-Elliott, B.A., Vasireddy, S., Vasireddy, R. et al. Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease. J Clin Microbiol. 2013;
51: 1747–1752
Google ScholarSee all References65], albeit rarely available in clinical laboratories. Recent experiences show that sequencing of the first 500 bp of the 16S rRNA gene (rrs) is sufficient to discriminate M. chimaera and M. intracellulare (included in MicroSeq; Applied Biosystems, Thermofisher, Foster City, CA, USA).
Another method is hsp65 sequencing [1x[1]Tortoli, E., Rindi, L., Garcia, M.J., Chiaradonna, P., Dei, R., Garzelli, C. et al. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov. Int J Syst Evol Microbiol. 2004;
54: 1277–1285
Google ScholarSee all References1]. Researchers have developed a novel reverse hybridization of PCR product-based assay (GenoType NTM-DR ver. 1.0; Hain Lifescience, Nehren, Germany) with 100% specificity for identifying M. chimaera in 173 isolates [66x[66]Mok, S., Rogers, T.R., and Fitzgibbon, M. Evaluation of GenoType NTM-DR assay for identification of Mycobacterium chimaera. J Clin Microbiol. 2017;
55: 1821–1826
Google ScholarSee all References66,67x[67]Lecorche, E., Haenn, S., Mougari, F., Kumanski, S., Veziris, N., Benmansour, H. et al. Comparison of methods available for identification of Mycobacterium chimaera. Clin Microbiol Infect. 2018;
24: 409–413
Google ScholarSee all References67]. Because the differentiation of MAC species is challenging and expensive in a diagnostic setting, Bruker has recently developed an improved algorithm to differentiate pathogenic species based on differential spectral peak signatures, by matrix-assisted laser desorption-ionization time of flight mass spectrometry on a commercially available platform. The results are promising with identification of 100% of the M. intracellulare and 82% of the M. chimaera isolates [68x[68]Epperson, L.E., Timke, M., Hasan, N.A., Godo, P., Durbin, D., Helstrom, N.K. et al. Evaluation of a novel MALDI biotyper algorithm to distinguish Mycobacterium intracellulare from Mycobacterium chimaera. Front Microbiol. 2018;
9: 3140
Google ScholarSee all References68].
A TaqMan quantitative polymerase chain reaction (qPCR) assay has been developed to facilitate a rapid diagnosis of M. chimaera infection [69x[69]Zozaya-Valdes, E., Porter, J.L., Coventry, J., Fyfe, J.A., Carter, G.P., da Silva, A.G. et al. A target-specific assay for rapid and quantitative detection of Mycobacterium chimaera DNA. J Clin Microbiol. 2017;
55: 1847–1856
Google ScholarSee all References69]. With this method, M. chimaera could be detected ex vivo at low concentrations (with a limit of 100 cfu/mL in whole blood) in human blood samples [69x[69]Zozaya-Valdes, E., Porter, J.L., Coventry, J., Fyfe, J.A., Carter, G.P., da Silva, A.G. et al. A target-specific assay for rapid and quantitative detection of Mycobacterium chimaera DNA. J Clin Microbiol. 2017;
55: 1847–1856
Google ScholarSee all References69]. Of note, blood anticoagulated with sodium citrate or EDTA and not heparin should be used for PCR testing.
Whole genome sequencing
For genotyping, whole genome sequencing of clinical and HCD isolates should be the preferred method to confirm relatedness to the HCD outbreak strain [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8,26x[26]Perkins, K.M., Lawsin, A., Hasan, N.A., Strong, M., Halpin, A.L., Rodger, R.R. et al. Notes from the field: Mycobacterium chimaera contamination of heater–cooler devices used in cardiac surgery – United States. Morb Mortal Wkly Rep. 2016;
65: 1117–1118
Google ScholarSee all References, 27x[27]Williamson, D., Howden, B., and Stinear, T. Mycobacterium chimaera spread from heating and cooling units in heart surgery. New Engl J Med. 2017;
376: 600–602
Google ScholarSee all References, 28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References,37x[37]Svensson, E., Jensen, E.T., Rasmussen, E.M., Folkvardsen, D.B., Norman, A., and Lillebaek, T. Mycobacterium chimaera in heater–cooler units in denmark related to isolates from the United States and United Kingdom. Emerg Infect Dis. 2017;
23
Google ScholarSee all References37,70x[70]Hasan, N.A., Epperson, L.E., Lawsin, A., Rodger, R.R., Perkins, K.M., Halpin, A.L. et al. Genomic analysis of cardiac surgery-associated Mycobacterium chimaera infections, United States. Emerg Infect Dis. 2019;
25: 559–563
Google ScholarSee all References70]. Phylogenetic signature SNPs can also be used to identify certain groups/clades of M. chimaera, including the outbreak clade [28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References28]. KARIUS (Redwood City, CA, USA) developed a next generation sequencing test specifically to detect M. chimaera in plasma samples [71x[71]Nomura, J., Rieg, G., Bluestone, G., Townson Tsai, T., Lai, A., Dryjanski-Yanovsky, J. et al. Rapid detection of invasive Mycobacterium chimaera infection by using a novel plasma-based next-generation sequencing assay. Open Forum Infect Dis. 2017;
4: S174
Google ScholarSee all References71,72x[72]Nomura, J., Rieg, G., Bluestone, G., Tsai, T., Lai, A., Terashita, D. et al. Rapid detection of invasive Mycobacterium chimaera disease via a novel plasma-based next-generation sequencing test. BMC Infect Dis. 2019;
19: 371
Google ScholarSee all References72].
Remarkably, whole genome sequencing results have supported a common source of the current global M. chimaera outbreak. Most studies revealed that the majority of patient isolates, HCD water and air isolates from multiple countries were very closely related with differences of single nucleotide polymorphisms of fewer than 10 variants [8x[8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017;
64: 335–342
Google ScholarSee all References8,26x[26]Perkins, K.M., Lawsin, A., Hasan, N.A., Strong, M., Halpin, A.L., Rodger, R.R. et al. Notes from the field: Mycobacterium chimaera contamination of heater–cooler devices used in cardiac surgery – United States. Morb Mortal Wkly Rep. 2016;
65: 1117–1118
Google ScholarSee all References, 27x[27]Williamson, D., Howden, B., and Stinear, T. Mycobacterium chimaera spread from heating and cooling units in heart surgery. New Engl J Med. 2017;
376: 600–602
Google ScholarSee all References, 28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References,37x[37]Svensson, E., Jensen, E.T., Rasmussen, E.M., Folkvardsen, D.B., Norman, A., and Lillebaek, T. Mycobacterium chimaera in heater–cooler units in denmark related to isolates from the United States and United Kingdom. Emerg Infect Dis. 2017;
23
Google ScholarSee all References37,70x[70]Hasan, N.A., Epperson, L.E., Lawsin, A., Rodger, R.R., Perkins, K.M., Halpin, A.L. et al. Genomic analysis of cardiac surgery-associated Mycobacterium chimaera infections, United States. Emerg Infect Dis. 2019;
25: 559–563
Google ScholarSee all References70]. One large European sequencing study [28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References28] included 250 isolates of M. chimaera and all but one isolate from a patient with prior open-heart surgeries clustered in the outbreak group 1.1 (median of only four SNP differences among them). This group also included HCD water and air isolates and one isolate from the LivaNova factory and a Maquet ECMO device. However, there were several HCD isolates not clustering in group 1.1. Additionally, two studies revealed that M. chimaera could be detected in factory-new assembled HCDs and from the pump assembly area [28x[28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017;
17: 1033–1041
Google ScholarSee all References28,30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016;
21
Google ScholarSee all References30] implicating contamination with M. chimaera at the LivaNova factory as the most likely source of the world-wide outbreak. Most researchers are concerned that all HCDs made by this manufacturer over the past decade may have been contaminated with the M. chimaera outbreak strain [37x[37]Svensson, E., Jensen, E.T., Rasmussen, E.M., Folkvardsen, D.B., Norman, A., and Lillebaek, T. Mycobacterium chimaera in heater–cooler units in denmark related to isolates from the United States and United Kingdom. Emerg Infect Dis. 2017;
23
Google ScholarSee all References37].
Microbiological diagnostic algorithm for suspected M. chimaera infection
Recommendations:
- •
Among patients with prosthetic valves/rings, aortic grafts and mechanical circulatory devices, conventional blood cultures off antibiotics are recommended for any undefined febrile illness for which antimicrobials are being considered (Class I, Level C).
- •
If the above are negative and cardiovascular infection is still in the differential based on when patient was exposed to 3T-HCD, multiple mycobacterial (heparin or sodium citrate) blood cultures are recommended (Class I, Level C). Consider also specific mycobacterium genus-specific PCR from whole blood (Class IIa, Level C).
- •
Acid-fast bacilli stain and culture of cardiac or other affected tissue (sputum, urine, kidney, liver, skin) are recommended (Class I, Level C). Consider also species-specific PCR or mycobacterium genus-specific PCR followed by next generation sequencing (NGS) from plasma (Class IIa, Level C).
- •
If cytopenias are present, bone marrow biopsy should be considered for histology, staining and mycobacterial culture (Class IIa, Level C).
- •
In case of fever of unknown origin (FUO), if initial mycobacteria blood cultures are unrevealing repeat mycobacterial blood cultures and mycobacterium genus-specific PCR from whole blood or NGS from plasma should be considered (Class IIa, Level C).
Early detection of cardiovascular infection (regardless of pathogen) is important. Most of the time the pathogen will not be M. chimaera. Therefore, blood cultures off antibiotics are important, and physicians need to routinely encourage all patients with cardiac valves, repairs, or history of infective endocarditis to request blood cultures before being placed on empiric antimicrobials for a febrile illness [73x[73]Chairs ASToIECGWC, Pettersson, G.B., Coselli, J.S., Writing, C., Pettersson, G.B., Coselli, J.S. et al. The American Association for Thoracic Surgery (AATS) consensus guidelines: surgical treatment of infective endocarditis: executive summary. J Thoracic Cardiovasc Surg 2017. 2016;
153 (1241–1258 e29)
Google ScholarSee all References73].
The crucial point in patients with suspected M. chimaera infection is a prior history of surgery requiring CPB (exposure criterion). When conventional blood cultures are negative and infective endocarditis or aortic graft infection is suspected, serological testing as suggested for culture-negative endocarditis should be done [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31]. Bacterial blood cultures (i.e non-mycobacterial) should be incubated for at least 7–10 days, while mycobacterial blood cultures should be incubated for at least 56 days. In cases involving redo cardiac surgery, tissue cultures (for both bacteria as well as mycobacteria), broad-range and mycobacterium genus-specific PCR (covering NTM) as well as histopathology should be performed. A laboratory diagnostic algorithm in case of suspected M. chimaera infection is provided in Figure 1Figure 1.
Figure 1
An algorithm for microbiological diagnosis of suspected cardiovascular infections including possible M. chimaera infections. IE, infective endocarditis; PCR, polymerase chain reaction; AFB, acid-fast bacilli; MALDI-TOF, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (adapted from [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31]). *Among patients meeting exposure criterion and a having a suggestive clinic consider upfront AFB cultures.
Histopathological diagnosis of M. chimaera infection
Recommendation
- •
Resected cardiac valve or other infected tissue and embolic fragments should be examined for possible mycobacterial infection (Class I, Level C).
- •
Mycobacterium genus-specific PCR should be considered if histopathology shows non-caseating granulomas and foamy swollen macrophages with/without acid-fast bacilli (Class IIa, Level C).
The histopathological standard to confirm a diagnosis of infective endocarditis in patients undergoing surgery for proven or suspected endocarditis is the presence of inflammation, neovascularization and organisms. Acid-fast bacilli stains from unfixed valve tissue should be done in all cases if a pathogen is not identified by conventional bacteriological methods. The detection of non-caseating granulomas and foamy swollen macrophages with/without acid-fast bacilli is consistent with NTM infection, including those by M. chimaera in the appropriate clinical setting [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,5x[5]Zweifel, S.A., Mihic-Probst, D., Curcio, C.A., Barthelmes, D., Thielken, A., Keller, P.M. et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Ophthalmology. 2017;
124: 178–188
Google ScholarSee all References5,7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7]. Granulomatous lesions have also been described in the liver, kidney, lung, choroid, bone, myocardium, bone marrow, skin and muscles among patients with disseminated M. chimaera infection [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,18x[18]Shafizadeh, N., Hale, G., Bhatnagar, J., Alshak, N.S., and Nomura, J. Mycobacterium chimaera hepatitis: a new disease entity. Am J Surg Pathol. 2019;
43: 244–250
Google ScholarSee all References18]. Resected cardiac valve or other infected tissue and embolic fragments should be examined for suspected mycobacterial infection. Additionally, the tissue sample should be sent to a microbiology laboratory for identification of microorganisms and performance of mycobacterium genus-specific PCR [74x[74]Deggim-Messmer, V., Bloemberg, G.V., Ritter, C., Voit, A., Homke, R., Keller, P.M. et al. Diagnostic molecular mycobacteriology in regions with low tuberculosis endemicity: combining real-time PCR assays for detection of multiple mycobacterial pathogens with line probe assays for identification of resistance mutations. EBioMedicine. 2016;
9: 228–237
Google ScholarSee all References74]. Because the sensitivity of PCRs performed on paraffin-embedded specimens is generally lower as compared to that of natural specimens [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,75x[75]Marchetti, G., Gori, A., Catozzi, L., Vago, L., Nebuloni, M., Rossi, M.C. et al. Evaluation of PCR in detection of Mycobacterium tuberculosis from formalin-fixed, paraffin-embedded tissues: comparison of four amplification assays. J Clin Microbiol. 1998;
36: 1512–1517
Google ScholarSee all References75] a short amplicon PCR targeting the mycobacterial hsp65 gene may be considered [76x[76]Zimmermann, D.R., Stadeli-Brodbeck, R., Ajmo, M., Dours-Zimmermann, M.T., Pfyffer, G.E., and Heitz, P.U. Molecular pathologic detection of mycobacteria. Verh Dtsch Ges Pathol. 1997;
81: 273–280
Google ScholarSee all References76].
Diagnostic criteria
Diagnostic criteria for M. chimaera infection are presented in Table VTable V. The long latency and the protean clinical presentation complicate securing an early diagnosis. Thus, the criteria used in the 2015 European Society of Cardiology guidelines for the diagnosis of IE [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31] are not applicable in these patients. Moreover, sporadic cases with bacteraemia and disseminated infections without obvious signs of valve involvement have occurred [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,49x[49]Asadi, T., Mullin, K., Roselli, E., Johnston, D., Tan, C.D., Rodriguez, E.R. et al. Disseminated Mycobacterium chimaera infection associated with heater–cooler units after aortic valve surgery without endocarditis. J Thoracic Cardiovasc Surg. 2018;
155: 2369–2374
Google ScholarSee all References49].
Antimicrobial therapy
Antimicrobial therapy
Recommendations
- •
Use of combination therapy with azithromycin (or clarithromycin) with ethambutol, and a rifamycin (Class I, Level C), whereby the macrolide is the cornerstone of therapy, thus should not be given as a monotherapy at any time (Class III, Level C).
- •
Amikacin is recommended and continued as long as tolerated via peripherally inserted central catheter (PICC) as outpatient parenteral antibiotic therapy (OPAT) (Class IIa, Level C).
Table VITable VI displays regimens for M. chimaera treatment. Currently, we are unable to provide a definitive recommendation regarding the duration of treatment. However, some investigators have followed with monthly mycobacterial blood cultures and treatment for a minimum of 12 months after conversion of blood cultures or redo surgery. For patients who are not candidates for additional cardiovascular surgery, long-term suppressive antibiotic therapy such as used in disseminated MAC infection might be considered.
| Type of Mycobacterium chimaera strain | Suggested regimen | Class | Level |
|---|---|---|---|
| Wild-type Mycobacterium chimaera | |||
| First line therapy | Azithromycin, rifampin (rifabutin), ethambutol, amikacinb | I | C |
| Second line therapy | Clarithromycin, rifabutin (rifampin), ethambutol, amikacinb | I | C |
| Drug-resistant Mycobacterium chimaeraa | |||
| Clarithromycin | Rifabutin/rifampin, ethambutol, amikacin, clofazimineb,c,d | I | C |
| Amikacin | Clarithromycin, rifabutin/rifampin, ethambutol, clofazimine c,d | ||
Google ScholarSee all References80].
Combination therapy consisting of azithromycin (or clarithromycin) with ethambutol, and a rifamycin is recommended for treatment of disseminated MAC infections among people living with HIV infection [47x[47]Griffith, D.E., Aksamit, T., Brown-Elliott, B.A., Catanzaro, A., Daley, C., Gordin, F. et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Resp Crit Care Med. 2007;
175: 367–416
Google ScholarSee all References47]. A macrolide is considered the cornerstone of therapy for MAC infections [47x[47]Griffith, D.E., Aksamit, T., Brown-Elliott, B.A., Catanzaro, A., Daley, C., Gordin, F. et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Resp Crit Care Med. 2007;
175: 367–416
Google ScholarSee all References47], whereas the combination with a rifamycin is to prevent macrolide resistance selection. Drug–drug interaction due to azithromycin and the rifamycins are less [77x[77]Koh, W.J., Jeong, B.H., Jeon, K., Lee, S.Y., and Shin, S.J. Therapeutic drug monitoring in the treatment of Mycobacterium avium complex lung disease. Am J Resp Crit Care Med. 2012;
186: 797–802
Google ScholarSee all References77] and the azithromycin tolerability is in general better than clarithromycin, thus azithromycin is preferred over clarithromycin. We strongly discourage one- or two-drug therapy (especially macrolide monotherapy) due to subsequent rapid development of macrolide resistance due to a 23S rRNA gene mutation [47x[47]Griffith, D.E., Aksamit, T., Brown-Elliott, B.A., Catanzaro, A., Daley, C., Gordin, F. et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Resp Crit Care Med. 2007;
175: 367–416
Google ScholarSee all References47,78x[78]Morimoto, K., Namkoong, H., Hasegawa, N., Nakagawa, T., Morino, E., Shiraishi, Y. et al. Macrolide-resistant Mycobacterium avium complex lung disease: analysis of 102 consecutive cases. Ann Am Thorac Soc. 2016;
13: 1904–1911
Google ScholarSee all References78,79x[79]Brown-Elliott, B.A., Nash, K.A., and Wallace, R.J. Jr. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev. 2012;
25: 545–582
Google ScholarSee all References79] and of amikacin resistance due to a 16S rRNA gene mutation [79x[79]Brown-Elliott, B.A., Nash, K.A., and Wallace, R.J. Jr. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev. 2012;
25: 545–582
Google ScholarSee all References79]. This resistance has been observed in disseminated disease due to HIV and in pulmonary disease treated with these agents.
During the initial (and perioperative) phase, intravenous amikacin is recommended for six to twelve weeks to increase the speed of sterilization of blood cultures and valves/abscesses, and subsequently amikacin treatment should be continued as long as tolerated. Due to the severity of M. chimaera infection, many clinicians added a fifth antimicrobial agent to the regimen, such as clofazimine, which in vitro has shown synergistic effects with amikacin [80x[80]van Ingen, J., Totten, S.E., Helstrom, N.K., Heifets, L.B., Boeree, M.J., and Daley, C.L. In vitro synergy between clofazimine and amikacin in treatment of nontuberculous mycobacterial disease. Antimicrob Agents Chemother. 2012;
56: 6324–6327
Google ScholarSee all References80]. Moxifloxacin [81x[81]Koh, W.J., Hong, G., Kim, S.Y., Jeong, B.H., Park, H.Y., Jeon, K. et al. Treatment of refractory Mycobacterium avium complex lung disease with a moxifloxacin-containing regimen. Antimicrob Agents Chemother. 2013;
57: 2281–2285
Google ScholarSee all References81] or linezolid are alternatives; however, since the modal MICs of moxifloxacin and linezolid are high this is of questionable benefit [82x[82]Maurer, F.P., Pohle, P., Kernbach, M., Sievert, D., Hillemann, D., Rupp, J. et al. Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium–intracellulare complex. Clin Microbiol Infect. 2019;
25 (379.e1–379.e7)
Google ScholarSee all References82]. There are limited in-vitro data regarding antibacterial activity of bedaquiline against MAC [62x[62]van Ingen, J. Microbiological diagnosis of nontuberculous mycobacterial pulmonary disease. Clin Chest Med. 2015;
36: 43–54
Google ScholarSee all References62,83x[83]Ruth, M.M., Sangen, J.J.N., Remmers, K., Pennings, L.J., Svensson, E., Aarnoutse, R.E. et al. A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria. J Antimicrob Chemother. 2019;
74: 935–943
Google ScholarSee all References, 84x[84]Philley, J.V., Wallace, R.J. Jr., Benwill, J.L., Taskar, V., Brown-Elliott, B.A., Thakkar, F. et al. Preliminary results of bedaquiline as salvage therapy for patients with nontuberculous mycobacterial lung disease. Chest. 2015;
148: 499–506
Google ScholarSee all References, 85x[85]Martin, A., Godino, I.T., Aguilar-Ayala, D.A., Mathys, V., Lounis, N., and Villalobos, H.R. In vitro activity of bedaquiline against slow-growing nontuberculous mycobacteria. J Med Microbiol. 2019;
68: 1137–1139
Google ScholarSee all References], although off-label use for M. chimaera treatment has been reported in several countries.
Adverse drug reactions of antimicrobial agents and therapeutic drug monitoring
Recommendations
- •
Monitoring of vestibular function and audiograms is recommended (monthly in patients receiving amikacin, every second month in patients receiving macrolides) (Class I, Level C).
- •
Periodic ophthalmologic examinations with visual acuity, red-green colour discrimination, confrontation visual field testing and dilated fundus examination are recommended in patients receiving ethambutol, linezolid and/or rifabutin (Class I, Level C).
- •
Monthly electrocardiograms are recommended in patients receiving macrolides, quinolones, clofazimine, linezolid and bedaquiline (Class I, Level C).
- •
Weekly therapeutic drug monitoring (TDM) is recommended in patients receiving amikacin. In patients with renal insufficiency receiving ethambutol, TDM is recommended at baseline and until steady state of therapeutic levels (Class I, Level C).
- •
Monitoring of macrolide blood levels may be considered especially when rifampin is combined with clarithromycin (Class IIb, Level C).
Many patients with disseminated M. chimaera infection experience adverse drug reactions [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7] due to innate toxicity. Anti-mycobacterial antibiotics with M. chimaera activity and their more common adverse drug reactions are listed in Table VIITable VII. Auditory and vestibular function can be impaired by amikacin, clarithromycin and azithromycin, and vestibular function screening and audiograms should be monitored. In addition, renal function should be monitored at least once weekly in patients who receive amikacin. Due to increased ocular toxicity of ethambutol, rifabutin and linezolid [86x[86]Griffith, D.E., Brown-Elliott, B.A., Shepherd, S., McLarty, J., Griffith, L., and Wallace, R.J. Jr. Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease. Am J Resp Crit Care Med. 2005;
172: 250–253
Google ScholarSee all References86], baseline and then periodic ophthalmologic examinations with visual acuity (ethambutol/rifabutin), red-green colour discrimination (ethambutol) and dilated fundus examination are recommended. This is needed if they have infection-related and/or IRIS-related ocular involvement [52x[52]Boni, C., Al-Sheikh, M., Hasse, B., Eberhard, R., Kohler, P., Hasler, P. et al. Multimodal imaging of choroidal lesions in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Retina. 2019;
39: 452–464
Google ScholarSee all References52]. Due to the risk of QTc-interval prolongation (associated with macrolide/rifabutin/bedaquiline/moxifloxacin and linezolid treatment) monthly electrocardiograms are recommended.
| Antibiotic | Dosagea | Route | Comments/side-effects |
|---|---|---|---|
| Azithromycin | 250–500 mg four times a dayb or 500 mg three times per week | Oral/IV | May prolong QTc interval. Reversible hearing impairment. Diarrhoea. Toxicities are dose- and serum-level-related. |
| Clarithromycin | 500 mg twice a dayb | Oral/IV | May prolong QTc interval. Frequent gastrointestinal toxicities such as metallic taste, diarrhoea, nausea, vomiting and elevated liver function tests. Toxicities are dose- and serum-level-related. |
| Ethambutol | 15 mg/kg body weight four times a day 25 mg/kg three times per weekc | Oral | Retrobulbar optic neuritis with visual loss; baseline and as needed testing of visual acuity and colour discrimination (Ishihara tests) is recommended as well as careful instructions to patientd |
| Rifampin | 600 mg four times a day | Oral/IV | Monitor for hepatotoxicity; drugs metabolized by cytochrome P-450 may require dose adjustments (e.g. macrolides, oral contraceptives, methadone, warfarin, and ART). Gastrointestinal reactions are common; orange discoloration of bodily fluids. Hypersensitivity reaction. |
| Rifabutin | 150–300 mg four times a day or 150–300 mg three times per weeke | Oral/IV | Monitor for hepatotoxicity; drugs metabolized by cytochrome P-450 may require dose adjustments (e.g. macrolides, oral contraceptives, methadone, warfarin, and ART). Fever. Anterior uveitis; bone marrow suppression; pseudojaundice (skin discoloration with normal bilirubin); polyarthralgias; ‘flu-like’ illness. |
| Amikacin | 15 mg/kg four times a dayf or 25 mg/kg three times per week | IV | Monitoring of renal function and vestibular/hearing function necessary. TDM required. |
| Companion drugs (not clearly proven efficacy) | |||
| Clofazimine | 100–200 mg four times a day | Oral | May prolong QTc interval. Consider reduction of dosage to five times per week in case of severe skin discoloration. Skin discoloration is usually reversible. Abdominal pain and/or eye symptoms. |
| Bedaquiline | Weeks 1+2: 400 mg four times a day Weeks 3–24: 200 mg three times per week | Oral | Take with food. Electrolyte abnormalities, hepatotoxicity, pancreatitis, myopathy. May prolong QTc interval, especially when concurrently used with moxifloxacin. Very little efficacy data [84x[84]Philley, J.V., Wallace, R.J. Jr., Benwill, J.L., Taskar, V., Brown-Elliott, B.A., Thakkar, F. et al. Preliminary results of bedaquiline as salvage therapy for patients with nontuberculous mycobacterial lung disease. Chest. 2015;
148: 499–506 Google ScholarSee all References84]. |
| Moxifloxacin | 400 mg four times a day | Oral/IV | Gastrointestinal disturbance: nausea and bloating. Neurologic effects: dizziness, insomnia, tremulousness, and headache. May prolong QTc interval. Very little efficacy data [81x[81]Koh, W.J., Hong, G., Kim, S.Y., Jeong, B.H., Park, H.Y., Jeon, K. et al. Treatment of refractory Mycobacterium avium complex lung disease with a moxifloxacin-containing regimen. Antimicrob Agents Chemother. 2013;
57: 2281–2285 Google ScholarSee all References81]. |
| Linezolidb | 600 mg four times a day/twice a day | Oral/IV | Risk of lactic acidosis, bone marrow suppression, and neurological toxicity (peripheral neuropathy). |
IV, intravenous; ART, antiretroviral therapy; TDM, therapeutic drug monitoring.
Google ScholarSee all References88,89x[89]Jeong, B.H., Jeon, K., Park, H.Y., Moon, S.M., Kim, S.Y., Lee, S.Y. et al. Peak plasma concentration of azithromycin and treatment responses in Mycobacterium avium complex lung disease. Antimicrob Agents Chemother. 2016; 60: 6076–6083
Google ScholarSee all References89].
Therapeutic drug monitoring (TDM) is always recommended in patients receiving amikacin treatment, and more closely in patients with impaired renal function. Clarithromycin enhances rifabutin toxicity (especially uveitis), whereas rifampicin lowers clarithromycin serum drug levels [77x[77]Koh, W.J., Jeong, B.H., Jeon, K., Lee, S.Y., and Shin, S.J. Therapeutic drug monitoring in the treatment of Mycobacterium avium complex lung disease. Am J Resp Crit Care Med. 2012;
186: 797–802
Google ScholarSee all References77,87x[87]Magis-Escurra, C., Alffenaar, J.W., Hoefnagels, I., Dekhuijzen, P.N., Boeree, M.J., van Ingen, J. et al. Pharmacokinetic studies in patients with nontuberculous mycobacterial lung infections. Int J Antimicrob Agents. 2013;
42: 256–261
Google ScholarSee all References87]. However, this has not been shown to impact clinical outcome. Since low macrolide drug concentrations due to drug–drug interactions have been described [88x[88]van Ingen, J., Egelund, E.F., Levin, A., Totten, S.E., Boeree, M.J., Mouton, J.W. et al. The pharmacokinetics and pharmacodynamics of pulmonary Mycobacterium avium complex disease treatment. Am J Resp Crit Care Med. 2012;
186: 559–565
Google ScholarSee all References88], monitoring for azithromycin or clarithromycin blood levels should be considered among all patients with M. chimaera infection [89x[89]Jeong, B.H., Jeon, K., Park, H.Y., Moon, S.M., Kim, S.Y., Lee, S.Y. et al. Peak plasma concentration of azithromycin and treatment responses in Mycobacterium avium complex lung disease. Antimicrob Agents Chemother. 2016;
60: 6076–6083
Google ScholarSee all References89].
Susceptibility to antimicrobial agents
Recommendations:
- •
Antimicrobial susceptibility testing of M. chimaera isolates should be performed by experienced reference laboratories (Class I, Level C).
- •
M. chimaera isolates should be saved for future testing if no baseline AST has been performed (Class I, Level C).
- •
Clarithromycin and amikacin MIC testing is recommended (Class I, Level C).
Criteria for antimicrobial susceptibility testing (AST) of NTM were established by the Clinical and Laboratory Standards Institute (CLSI) in November 2018. Breakpoints for antimicrobials used in the treatment of NTM infections were re-defined in the M24Ed3 [90x[90]Woods, G.L. Susceptibility testing of mycobacteria, Nocardia spp., and other aerobic actinomycetes. 3rd edition. Clinical and Laboratory Standards Institute,
Wayne, PA; 2018 (CLSI document M24Ed3)
Google ScholarSee all References90] and M62Ed1 [91x[91]Woods, G.L. Performance standards for susceptibility testing of mycobacteria, nocardia spp. and other aerobic actinomycetes. CLSI doument M62Ed1. Clinical and Laboratory Standards Institute,
Wayne, PA; 2018
Google ScholarSee all References91] CLSI documents, respectively. To ensure optimal results, AST of M. chimaera isolates should be performed by experienced reference laboratories [92x[92]Nikolayevskyy, V., Maurer, F.P., Holicka, Y., Taylor, L., Liddy, H., and Kranzer, K. Novel external quality assurance scheme for drug susceptibility testing of non-tuberculous mycobacteria: a multicentre pilot study. J Antimicrob Chemother. 2019;
74: 1288–1294
Google ScholarSee all References92]. Baseline macrolide AST should be performed for clarithromycin, as the solubility at high concentrations is increased as compared to that of azithromycin [79x[79]Brown-Elliott, B.A., Nash, K.A., and Wallace, R.J. Jr. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev. 2012;
25: 545–582
Google ScholarSee all References79,93x[93]Woods, G.L. Susceptibility testing of mycobacteria, nocardia, and other aerobic actinomycetes; approved standard. CLSI document M24-A2. Clinical and Laboratory Standards Institute,
Wayne, PA; 2011
Google ScholarSee all References93,94x[94]Woods, G.L. Susceptibility testing of mycobacteria, nocardia and other aerobic actinomycetes; approved standard. NCCLS document M24-A. National Committee for Clinical Laboratory Standards,
Wayne, PA; 2003
Google ScholarSee all References94]. Furthermore AST is recommended for (i) blood culture isolates from patients receiving macrolides (ii) clinically significant isolates of patients who received macrolide treatment and (iii) isolates recovered from patients with relapsing infection following completion of a macrolide-containing regimen. As in other clinically relevant NTM infections, M. chimaera isolates should be saved for future testing if no baseline AST has been performed [79x[79]Brown-Elliott, B.A., Nash, K.A., and Wallace, R.J. Jr. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev. 2012;
25: 545–582
Google ScholarSee all References79,93x[93]Woods, G.L. Susceptibility testing of mycobacteria, nocardia, and other aerobic actinomycetes; approved standard. CLSI document M24-A2. Clinical and Laboratory Standards Institute,
Wayne, PA; 2011
Google ScholarSee all References93,94x[94]Woods, G.L. Susceptibility testing of mycobacteria, nocardia and other aerobic actinomycetes; approved standard. NCCLS document M24-A. National Committee for Clinical Laboratory Standards,
Wayne, PA; 2003
Google ScholarSee all References94].
The minimum inhibitory concentration (MIC) of antimicrobials to which an organism's growth is inhibited (in μg/mL, indexed to base 1) should be determined in slowly growing mycobacteria by broth microdilution in Mueller Hinton broth [93x[93]Woods, G.L. Susceptibility testing of mycobacteria, nocardia, and other aerobic actinomycetes; approved standard. CLSI document M24-A2. Clinical and Laboratory Standards Institute,
Wayne, PA; 2011
Google ScholarSee all References93,94x[94]Woods, G.L. Susceptibility testing of mycobacteria, nocardia and other aerobic actinomycetes; approved standard. NCCLS document M24-A. National Committee for Clinical Laboratory Standards,
Wayne, PA; 2003
Google ScholarSee all References94]. All baseline M. chimaera clinical isolates regardless of source have very similar MICs to any drug. It remains unclear whether the fact that post-CPB surgery infections have a common source of infection contributes to the particular AST pattern. Wild-type M. chimaera strains are susceptible to macrolides [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,95x[95]Mok, S., Hannan, M.M., Nolke, L., Stapleton, P., O’Sullivan, N., Murphy, P. et al. Antimicrobial susceptibility of clinical and environmental Mycobacterium chimaera Isolates. Antimicrob Agents Chemother. 2019;
63
Google ScholarSee all References95] and, to date, no isolate with clarithromycin resistance has been recovered [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,82x[82]Maurer, F.P., Pohle, P., Kernbach, M., Sievert, D., Hillemann, D., Rupp, J. et al. Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium–intracellulare complex. Clin Microbiol Infect. 2019;
25 (379.e1–379.e7)
Google ScholarSee all References82]. One patient who received prolonged macrolide treatment and suffered infection relapse had an isolate that demonstrated intermediate resistance to clarithromycin (MIC of ≥16 to ≥32 μg/mL depending on pH) [52x[52]Boni, C., Al-Sheikh, M., Hasse, B., Eberhard, R., Kohler, P., Hasler, P. et al. Multimodal imaging of choroidal lesions in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Retina. 2019;
39: 452–464
Google ScholarSee all References52].
Routine susceptibility testing of anti-mycobacterial agents other than clarithromycin is not recommended [79x[79]Brown-Elliott, B.A., Nash, K.A., and Wallace, R.J. Jr. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev. 2012;
25: 545–582
Google ScholarSee all References79], since reported AST of rifampin, rifabutin, ethambutol and streptomycin do not predict therapeutic efficacy. However, we recommend primary testing of amikacin against MAC isolates, extrapolating breakpoints from rapidly growing mycobacteria (≤16 mg/L susceptible, 32 mg/L intermediate, and ≥64 mg/L resistant) [91x[91]Woods, G.L. Performance standards for susceptibility testing of mycobacteria, nocardia spp. and other aerobic actinomycetes. CLSI doument M62Ed1. Clinical and Laboratory Standards Institute,
Wayne, PA; 2018
Google ScholarSee all References91,96x[96]Brown-Elliott, B.A., Iakhiaeva, E., Griffith, D.E., Woods, G.L., Stout, J.E., Wolfe, C.R. et al. In vitro activity of amikacin against isolates of Mycobacterium avium complex with proposed MIC breakpoints and finding of a 16S rRNA gene mutation in treated isolates. J Clin Microbiol. 2013;
51: 3389–3394
Google ScholarSee all References96], since amikacin is a key component of regimens to treat complicated MAC infections and since it has often been used in the pre- and postoperative phase of M. chimaera infection [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,15x[15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016;
3: ofw131
Google ScholarSee all References15,82x[82]Maurer, F.P., Pohle, P., Kernbach, M., Sievert, D., Hillemann, D., Rupp, J. et al. Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium–intracellulare complex. Clin Microbiol Infect. 2019;
25 (379.e1–379.e7)
Google ScholarSee all References82].
Surgical intervention
Pre- and perioperative management
Recommendations on the perioperative management and the hospital epidemiology precautions for patients who require repeat surgery in the treatment of cardiovascular infection due to M. chimaera are summarized in Table VIIITable VIII. Coronary angiography and intraoperative echocardiography should be performed as recommended by the ESC guidelines [31x[31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015;
36: 3075–3128
Google ScholarSee all References31]. Recommendations for surgical site infection prophylaxis for cardiac procedures should be followed [97x[97]Bratzler, D.W., Dellinger, E.P., Olsen, K.M., Perl, T.M., Auwaerter, P.G., Bolon, M.K. et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;
70: 195–283
Google ScholarSee all References97]. In addition, M. chimaera treatment should be continued in the perioperative phase. Isolation precautions in the pre- and post-anaesthesia care unit are not required.
| Recommendation | Class | Level |
|---|---|---|
| Perform coronary angiography and intraoperative echocardiography | I | C |
Antimicrobial treatment
| IIa | C |
| I | C |
Pre- and post-anaesthesia care unit
| I IIb IIb IIb III III | C C C C C C |
OR, operating room.
Surgical approach
Recommendation
- •
Revision surgery with removal of all cardiovascular prosthetic material should be considered (Class IIa, Level C). Source control should include all extracardiac foci in addition to cardiovascular sites (Class IIa, Level C).
Cardiovascular M. chimaera infection is associated with a high morbidity and mortality due, in part, to both dissemination of infection and high affinity of mycobacteria to attach to and form biofilm on the surface of cardiovascular prosthetic devices. Many patients managed conservatively with anti-mycobacterial treatment alone have either failed to improve or have experienced breakthrough infection [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7]. Hence, redo surgery with removal of all cardiovascular prosthetic material should be considered. Intraoperative mycobacterial tissue cultures and mycobacterium genus-specific PCR followed by sequencing must be obtained because culture results have been positive in the bulk of patients, regardless of whether or not anti-mycobacterial therapy has been previously administered [9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9]. Removal of all intracardiac foreign material is strongly recommended due to mycobacterial biofilm formation, even if a cardiac valve/vascular graft is functioning well. Additionally, extraction and replacement of any other cardiovascular prosthetic devices is recommended. Patients with localized (e.g. sternal surgical site) infections should undergo extensive debridement with removal of sternal metal wires [3x[3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013;
51: 1769–1773
Google ScholarSee all References3,7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9,49x[49]Asadi, T., Mullin, K., Roselli, E., Johnston, D., Tan, C.D., Rodriguez, E.R. et al. Disseminated Mycobacterium chimaera infection associated with heater–cooler units after aortic valve surgery without endocarditis. J Thoracic Cardiovasc Surg. 2018;
155: 2369–2374
Google ScholarSee all References49]. Nevertheless, there are patients in whom extensive surgical intervention is not feasible, usually due to a patient's underlying co-morbid conditions, and an individualized approach to infection management is needed. The optimal timing of a redo cardiovascular surgical procedure remains undefined. If feasible, it may be prudent to wait for clearance of mycobacterial blood cultures. Several centres advise preoperative anti-mycobacterial therapy for 6–12 weeks to reduce the chance of planktonic forms seeding replacement devices [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,49x[49]Asadi, T., Mullin, K., Roselli, E., Johnston, D., Tan, C.D., Rodriguez, E.R. et al. Disseminated Mycobacterium chimaera infection associated with heater–cooler units after aortic valve surgery without endocarditis. J Thoracic Cardiovasc Surg. 2018;
155: 2369–2374
Google ScholarSee all References49]. Whether anti-mycobacterial therapy prior to surgery and removal of all prosthetic material influences infection cure rates remains to be defined by longer follow-up periods with a larger number of patients [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9,13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13,48x[48]Hasse, B. SY0821. Clinical management of Mycobacterium chimaera infection. ECCMID,
Austria; 2017 (Available at:)https://www.escmid.org/escmid_publications/escmid_elibrary/material/?mid=44559. ([last accessed October 2019])
Google ScholarSee all References48].
There is no preference for a specific valve/graft substitute as there are insufficient data to make a recommendation. The use of cryopreserved homografts should be considered in the setting of aortic graft infections and annular abscess formation. However, availability of human tissue for transplantation is an important consideration as not all institutions have access, especially in urgent cases. Heart transplantation is considered in extreme infective endocarditis cases where operative procedures fail, provided repeated blood cultures are negative. Due to the need for immunosuppression, heart transplantation for disseminated M. chimaera infection generally has not been considered a feasible option. Extrathoracic and disseminated M. chimaera infections are common. Ideally, non-cardiovascular foci (e.g. bone infections and abscesses) should be eradicated before cardiovascular surgical intervention [22x[22]O’Neil, C.R., Taylor, G., Smith, S., Joffe, A.M., Antonation, K., Shafran, S. et al. Mycobacterium chimaera infection after aortic valve replacement presenting with aortic dissection and pseudoaneurysm. Open Forum Infect Dis. 2018;
5: ofy018
Google ScholarSee all References22]. If cardiac surgery cannot be delayed, distant infection sites should be eradicated before the end of anti-mycobacterial therapy. In some cases, surgical intervention at non-cardiovascular infection sites will also be required.
Follow-up and prognosis
Relapse is a major complication of disseminated M. chimaera infection that often requires repetitive surgery involving cardiovascular and/or non-cardiovascular sites [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9,13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13]. Factors associated with relapse are included in Table IXTable IX. Currently, the actual infection relapse risk is undefined, in part related to the extended follow-up that is required after completion of anti-mycobacterial therapy to determine if cure of infection has been achieved. Among the few reported survivors with defined follow-up [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9], the relapse rate has been as high as 30–50%. However, the retrospective nature of most case series with broad-ranging follow-up periods and the prolonged incubation period of infection due to M. chimaera make quantitating outcome analyses difficult. Elevated mortality is another troubling outcome with recent case series reporting mortality rates of 20%–67% [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9,13x[13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. ; October 29th 2016 (Available at:)http://hhhtx/idsaconfexcom/idsa/2016/webprogram/Paper60925. ([last accessed April 2017])
Google ScholarSee all References13,14x[14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017;
23: 796–805
Google ScholarSee all References14,21x[21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. Ann Thorac Surg. 2017;
104 (e43–e5)
Google ScholarSee all References21,30x[30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016;
21
Google ScholarSee all References30].
| Delayed anti-mycobacterial treatment |
|---|
| No ‘lead-in’ preoperative anti-mycobacterial treatment |
| Positive M. chimaera valve culture |
| Cardiac or extrathoracic prosthetic material |
| Disseminated disease with distant foci and abscess formation |
| Macrolide and/or amikacin resistant M. chimaera strain |
Considerations for patient notification, screening and investigation
Recommendation
- •
Consider patient and provider notification regarding risk and signs/symptoms of infection (Class IIa, Level C)
- •
Additional case finding through investigation and testing of patients with a history of exposure to 3T-HCD should be restricted to those who are symptomatic (Table XTable X) (Class IIa, Level C).
View Table in HTMLTable XRecommendations for Mycobacterium chimaera infection patient/provider notification, additional case-finding and investigation, and screening Recommendation Class Level - •
Patient notification should be considered. However, to date, such notifications have not contributed substantially to case-finding. Discussion and input by health department authorities and likely consumer stakeholders needed.
IIa C - •
Provider notification should be considered and has been successful in case detection. M. chimaera infection can occur among patients with open-heart surgery with CPB after 2008 (earliest sentinel surgery) and before the introduction of effective risk mitigation measures.
IIa C - •
Additional case-finding through evaluation and testing of patients with a history of exposure to (3T-)HCD (past 5–6 years) should be restricted to those who are symptomatic and/or have at least one of the following:
- –
Culture-negative prosthetic valve endocarditis
- –
Culture-negative aortic graft infection
- –
Mechanical circulatory support device infection
- –
Culture-negative sternal osteomyelitis and/or mediastinitis
- –
Fever of unknown origin
- –
Vasculitis
- –
Undetermined systemic disease, sarcoidosis-like or other granulomatous disease
- –
IIa C - •
Diagnostic measures:
- –
Physical examination including ophthalmoscopy, medical history (weight loss, night sweats, fever, skeletal pain, etc.), blood tests (ESR, CRP, complete blood count, transaminases, creatinine)
- –
Mycobacterial blood cultures (BacTec myco Lytic/F bottles BD Bioscience); VersaTrek (Thermo Fisher) use of Isolator tubes (Isolator 10, Oxoid; Isostatw System, WampoleTM).
- –
Tissue mycobacterial cultures, broad range and mycobacterium-genus specific PCR and histopathological work-up in case of reoperative heart surgery or surgery of distant foci.
- –
I C - •
Additional case-finding tools:
- –
Review non-respiratory M. avium complex isolates and identify patients with former CPB with the use of 3T-HCD within 5–6 years.
- –
Review culture-negative prosthetic valve endocarditis/aortic graft infections and histopathology reports for manifestations compatible with a probable post-cardiac-surgery M. chimaera disease.
- –
Review sarcoidosis cases with former CPB within 5–6 years.
- –
Review histopathology reports from excised heart valves/aortic grafts for granulomatous tissue formation.
- –
IIb C - •
Routine screening of asymptomatic patients with a history of exposure to (3T-)HCD is not recommended.
III C HCD, heater–cooler device; CPB, cardiopulmonary bypass; CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; PCR, polymerase chain reaction.
- •
Patients who have undergone CPB should be educated about the risks, until they reach the 5th year anniversary of their surgery, so that patients can seek medical care if warning signs and symptoms of an M. chimaera infection develop. Given the higher yield among hospitals that already had a case (in addition to the medico-legal component), this recommendation applies in particular to sites with at least one case.
Providers who see exposed patients, such as primary care providers, should be notified to increase awareness of the risks associated with exposure to CPB. Provider awareness can be achieved through public health alerts, webinars, or emails to various healthcare provider professional societies. Additionally, the use of ‘alerts’ embedded in electronic medical records of patients who underwent open-chest surgery and may be at risk of future M. chimaera infection may allow providers to more rapidly diagnose and refer patients for infectious disease consultation.
Investigators in the United States have implemented both patient and healthcare provider notifications to help identify potentially infected patients early [98x[98]Jarashow, M.C., Terashita, D., Balter, S., and Schwartz, B. Notes from the field: Mycobacteria chimaera infections associated with heater–cooler unit use during cardiopulmonary bypass surgery – Los Angeles County, 2012–2016. Morb Mortal Wkly Rep. 2019;
67: 1428–1429
Google ScholarSee all References98,99x[99]Centers for Disease Control and Prevention. CDC advises hospitals to alert patients at risk from contaminated heater–cooler devices used during cardiac surgery. ; October 13th, 2016
Google ScholarSee all References99]. In 2016, CDC issued a recommendation that all US healthcare facilities using the 3T-HCD notify patients who underwent open-chest cardiac surgery using these devices of the risk of M. chimaera infection. Patient notification letters provided information on the signs and symptoms of a possible infection and patients were encouraged to promptly seek medical care if experiencing any of these symptoms [99x[99]Centers for Disease Control and Prevention. CDC advises hospitals to alert patients at risk from contaminated heater–cooler devices used during cardiac surgery. ; October 13th, 2016
Google ScholarSee all References99]. To date, a number of infected patients and clusters have been identified through this strategy, including one institution with a large outbreak that was not previously recognized [18x[18]Shafizadeh, N., Hale, G., Bhatnagar, J., Alshak, N.S., and Nomura, J. Mycobacterium chimaera hepatitis: a new disease entity. Am J Surg Pathol. 2019;
43: 244–250
Google ScholarSee all References18,98x[98]Jarashow, M.C., Terashita, D., Balter, S., and Schwartz, B. Notes from the field: Mycobacteria chimaera infections associated with heater–cooler unit use during cardiopulmonary bypass surgery – Los Angeles County, 2012–2016. Morb Mortal Wkly Rep. 2019;
67: 1428–1429
Google ScholarSee all References98]. Additionally, consideration should be given to patients who will be undergoing cardiac surgery with a 3T-HCD to notify them of the potential risks of M. chimaera infection through a preoperative informed consent process [100x[100]Marra, A.R., Diekema, D.J., and Edmond, M.B. Mycobacterium chimaera infections associated with contaminated heater–cooler devices for cardiac surgery: outbreak management. Clin Infect Dis. 2017;
65: 669–674
Google ScholarSee all References100].
The task force recommends that additional case finding through evaluation and testing be restricted to patients previously exposed to HCD who develop symptoms (Table XTable X), given the low disease incidence, the significant psychological impact and the overall costs of screening. Additional cases of M. chimaera infections might be found by review of (i) non-respiratory M. avium complex isolates with former CPB with the use of 3T-HCD within 5–6 years; (ii) review of histopathology reports of culture negative cardiovascular infections with former CPB with the use of 3T-HCD within 5–6 years; (iii) review of sarcoidosis cases and former CPB with the use of 3T-HCD within 5–6 years.
Recommendations regarding systematic screening for M. chimaera infection among asymptomatic patients with a prior history of open-chest surgery have been considered by several health agencies, with the assumption that this might result in an earlier diagnosis and a reduction in dissemination of infection. However, the time between index surgery and diagnosis of infection has been broad and ranged between 6 weeks to more than 5 years (median, 15 months) [9x[9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018;
24: 1164–1170
Google ScholarSee all References9,12x[12]Gasch, O., Meije, Y., Espasa, M., Font, B., Jimenez, S., and Fernandez-Hidalgo, N. Disseminated infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol (Engl Ed). 2019;
72: 502–503
Google ScholarSee all References12]; thus screening, if performed, would have to be done on a recurrent basis. Moreover, screening tools, such as routine and/or mycobacterial blood cultures, have a low sensitivity for detecting M. chimaera [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7]. In addition, it is not clear which screening tests might provide the greatest yield.
Prevention, infection control measures and reporting obligation
Co-ordination and surveillance of risk mitigation measures (Table XITable XI) should be the responsibility of each institution's infection prevention and control experts, who are familiar with the biology of M. chimaera and its proclivity to cause device contamination in certain settings. Institutions should also refer to relevant guidance from regional regulatory and public health providers. In particular, the preferential adherence of mycobacteria to surfaces at air–water interfaces and the high cell surface hydrophobicity contribute to the disinfection tolerance of mycobacteria [34x[34]Garvey, M.I., Ashford, R., Bradley, C.W., Bradley, C.R., Martin, T.A., Walker, J. et al. Decontamination of heater–cooler units associated with contamination by atypical mycobacteria. J Hosp Infect. 2016;
93: 229–234
Google ScholarSee all References34,41x[41]Schreiber, P.W., Kuster, S.P., Hasse, B., Bayard, C., Ruegg, C., Kohler, P. et al. Reemergence of Mycobacterium chimaera in heater–cooler units despite intensified cleaning and disinfection protocol. Emerg Infect Dis. 2016;
22: 1830–1833
Google ScholarSee all References41,103x[103]Percival, S.L., Suleman, L., Vuotto, C., and Donelli, G. Healthcare-associated infections, medical devices and biofilms: risk, tolerance and control. J Med Microbiol. 2015;
64: 323–334
Google ScholarSee all References, 104x[104]Gotting, T., Klassen, S., Jonas, D., Benk, C., Serr, A., Wagner, D. et al. Heater–cooler units: contamination of crucial devices in cardiothoracic surgery. J Hosp Infect. 2016;
93: 223–228
Google ScholarSee all References, 105x[105]Walker, J., Moore, G., Collins, S., Parks, S., Garvey, M.I., Lamagni, T. et al. Microbiological problems and biofilms associated with Mycobacterium chimaera in heater–cooler units used for cardiopulmonary bypass. J Hosp Infect. 2017;
96: 209–220
Google ScholarSee all References, 106x[106]Garvey, M.I., Bradley, C.W., and Walker, J. A year in the life of a contaminated heater–cooler unit with Mycobacterium chimaera?. Infect control hosp epidemiol. 2017;
38: 705–711
Google ScholarSee all References]. Additionally, NTM can grow over a very wide temperature range (15–45°C) and survive at 55–60°C [65x[65]Wallace, R.J. Jr., Iakhiaeva, E., Williams, M.D., Brown-Elliott, B.A., Vasireddy, S., Vasireddy, R. et al. Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease. J Clin Microbiol. 2013;
51: 1747–1752
Google ScholarSee all References65]. Since decontamination measures often fail [41x[41]Schreiber, P.W., Kuster, S.P., Hasse, B., Bayard, C., Ruegg, C., Kohler, P. et al. Reemergence of Mycobacterium chimaera in heater–cooler units despite intensified cleaning and disinfection protocol. Emerg Infect Dis. 2016;
22: 1830–1833
Google ScholarSee all References, 91x[91]Woods, G.L. Performance standards for susceptibility testing of mycobacteria, nocardia spp. and other aerobic actinomycetes. CLSI doument M62Ed1. Clinical and Laboratory Standards Institute,
Wayne, PA; 2018
Google ScholarSee all References, 92x[92]Nikolayevskyy, V., Maurer, F.P., Holicka, Y., Taylor, L., Liddy, H., and Kranzer, K. Novel external quality assurance scheme for drug susceptibility testing of non-tuberculous mycobacteria: a multicentre pilot study. J Antimicrob Chemother. 2019;
74: 1288–1294
Google ScholarSee all References] and since intensified cleaning and disinfection might lead to device damage [36x[36]Centers for Disease Control and Prevention. Non-tuberculous mycobacterium (NTM) infections and heater–cooler devices interim practical guidance. CDC,
Atlanta; October 2015 (Available at:)http://www.cdc.gov/HAI/pdfs/outbreaks/CDC-Notice-Heater-Cooler-Units-final-clean.pdf. ([last accessed March 2016])
Google ScholarSee all References36,106x[106]Garvey, M.I., Bradley, C.W., and Walker, J. A year in the life of a contaminated heater–cooler unit with Mycobacterium chimaera?. Infect control hosp epidemiol. 2017;
38: 705–711
Google ScholarSee all References106], facilities can either use other HCDs or they are strongly advised to separate HCDs from the OR room air volume by: (i) placing HCDs in dedicated utility rooms adjacent to the operating room (OR) [33x[33]Sommerstein, R., Schreiber, P.W., Diekema, D.J., Edmond, M.B., Hasse, B., Marschall, J. et al. Mycobacterium chimaera outbreak associated with heater–cooler devices: piecing the puzzle together. Infect Control Hosp Epidemiol. 2017;
38: 103–108
Google ScholarSee all References33,102x[102]Barker, T.A., Dandekar, U., Fraser, N., Dawkin, L., Sweeney, P., Heron, F. et al. Minimising the risk of Mycobacterium chimaera infection during cardiopulmonary bypass by the removal of heater–cooler units from the operating room. Perfusion. 2018;
33: 264–269
Google ScholarSee all References102,107x[107]Mertz, D., Macri, J., Hota, S., Amaratunga, K., Davis, I., Johnston, L. et al. Response to alert on possible infections with Mycobacterium chimaera from contaminated heater–cooler devices in hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP). Infect Control Hosp Epidemiol. 2018;
39: 482–484
Google ScholarSee all References107,108x[108]Ogunremi, T., Taylor, G., Johnston, L., Amaratunga, K., Muller, M., Coady, A. et al. Mycobacterium chimaera infections in post-operative patients exposed to heater–cooler devices: an overview. Can Commun Dis Rep. 2017;
43: 107–113
Google ScholarSee all References108] or (ii) placing them in encasings with controlled air extraction via a duct to the theatre exhaust conduit [41]. However, products such as encasings that are engineered and built by hospitals may alter the function of the HCD and the potential for such changes in function should be taken into consideration when implementing such interventions. Removal of HCDs from the OR may require reconfiguration of ORs and the theatre design may prevent removal of the implicated HCDs [108x[108]Ogunremi, T., Taylor, G., Johnston, L., Amaratunga, K., Muller, M., Coady, A. et al. Mycobacterium chimaera infections in post-operative patients exposed to heater–cooler devices: an overview. Can Commun Dis Rep. 2017;
43: 107–113
Google ScholarSee all References108]. If HCD exhaust air cannot be reliably separated from the OR, HCDs should be placed as far as possible away from the operating field and the vent exhaust should be directed away from the patient and the surgical instruments [107x[107]Mertz, D., Macri, J., Hota, S., Amaratunga, K., Davis, I., Johnston, L. et al. Response to alert on possible infections with Mycobacterium chimaera from contaminated heater–cooler devices in hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP). Infect Control Hosp Epidemiol. 2018;
39: 482–484
Google ScholarSee all References, 108x[108]Ogunremi, T., Taylor, G., Johnston, L., Amaratunga, K., Muller, M., Coady, A. et al. Mycobacterium chimaera infections in post-operative patients exposed to heater–cooler devices: an overview. Can Commun Dis Rep. 2017;
43: 107–113
Google ScholarSee all References, 109x[109]Food and Drug Administration. Update: availability of deep-cleaning service of certain LivaNova PLC (formerly Sorin Group Deutschland GmbH) Stӧckert 3T heater–cooler systems in the U.S.:. FDA Safety Communication,
; 2018 (Available at:)https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm610394.htm. ([last accessed March 2019])
Google ScholarSee all References]. These measures should be considered only temporary, as the risk of airborne transmission is not eliminated. Additionally, cross contamination by exchanging tubing from one HCD to another should be avoided [33x[33]Sommerstein, R., Schreiber, P.W., Diekema, D.J., Edmond, M.B., Hasse, B., Marschall, J. et al. Mycobacterium chimaera outbreak associated with heater–cooler devices: piecing the puzzle together. Infect Control Hosp Epidemiol. 2017;
38: 103–108
Google ScholarSee all References33,109x[109]Food and Drug Administration. Update: availability of deep-cleaning service of certain LivaNova PLC (formerly Sorin Group Deutschland GmbH) Stӧckert 3T heater–cooler systems in the U.S.:. FDA Safety Communication,
; 2018 (Available at:)https://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/ucm610394.htm. ([last accessed March 2019])
Google ScholarSee all References109].
| Topic | Recommendations | Class | Level |
|---|---|---|---|
| General guidelines for HCDs | |||
| HCD traceability | Register HCD, patient, and date of use [33x[33]Sommerstein, R., Schreiber, P.W., Diekema, D.J., Edmond, M.B., Hasse, B., Marschall, J. et al. Mycobacterium chimaera outbreak associated with heater–cooler devices: piecing the puzzle together. Infect Control Hosp Epidemiol. 2017;
38: 103–108 Google ScholarSee all References33] | I | C |
| Water safety | Use only sterile or all-bacteria-filtered-water (0.22 mm or less) including when making ice needed for patient cooling [101x[101]Allen, K.B., Yuh, D.D., Schwartz, S.B., Lange, R.A., Hopkins, R., Bauer, K. et al. Nontuberculous Mycobacterium infections associated with heater–cooler devices. Ann Thorac Surg. 2017;
104: 1237–1242 Google ScholarSee all References101] | IIa | C |
| Use cleaning and disinfection procedures according to the manufacturer | Maintain log of cleaning and disinfection Caveat: Current decontamination protocols may be insufficient due to biofilm formation by mycobacteria in the implicated devices [41x[41]Schreiber, P.W., Kuster, S.P., Hasse, B., Bayard, C., Ruegg, C., Kohler, P. et al. Reemergence of Mycobacterium chimaera in heater–cooler units despite intensified cleaning and disinfection protocol. Emerg Infect Dis. 2016; 22: 1830–1833 Google ScholarSee all References41,102x[102]Barker, T.A., Dandekar, U., Fraser, N., Dawkin, L., Sweeney, P., Heron, F. et al. Minimising the risk of Mycobacterium chimaera infection during cardiopulmonary bypass by the removal of heater–cooler units from the operating room. Perfusion. 2018; 33: 264–269 Google ScholarSee all References102]. Biofilm formation can be seen by discoloration/cloudiness in the fluid lines or circuits [101x[101]Allen, K.B., Yuh, D.D., Schwartz, S.B., Lange, R.A., Hopkins, R., Bauer, K. et al. Nontuberculous Mycobacterium infections associated with heater–cooler devices. Ann Thorac Surg. 2017; 104: 1237–1242 Google ScholarSee all References101]. | I | C |
| Separate HCD (other than 3T) exhaust air from ORa | Separation of HCDs from air volume of critical medical areas such as operating rooms may be considered. | IIb | C |
| Remove/replace contaminated 3T-HCD from service | All 3T-HCD manufactured should ideally be removed from service or alternatively measures ensuring strict separation between air in the OR and the potentially contaminated air around HCD should be taken. | I | C |
| Separate 3T-HCD exhaust air from OR | Guarantee strict separation of HCDs from air volume of critical medical areas such as operating rooms [35x[35]Sommerstein, R., Ruegg, C., Kohler, P., Bloemberg, G., Kuster, S.P., and Sax, H. Transmission of Mycobacterium chimaera from heater–cooler units during cardiac surgery despite an ultraclean air ventilation system. Emerg Infect Dis. 2016;
22: 1008–1013 Google ScholarSee all References35,102x[102]Barker, T.A., Dandekar, U., Fraser, N., Dawkin, L., Sweeney, P., Heron, F. et al. Minimising the risk of Mycobacterium chimaera infection during cardiopulmonary bypass by the removal of heater–cooler units from the operating room. Perfusion. 2018; 33: 264–269 Google ScholarSee all References102]. Place HCD outside the OR, whenever possible. Encase HCD connected to the OR exhaust. | I | C |
| Testing of HCD | |||
| Non-tuberculous mycobacterium surveillance | Use the ‘Protocol for case detection, laboratory diagnosis and environmental testing of M. chimaera infections potentially associated with heater–cooler units’ by ECDC [64x[64]European Centre for Disease Prevention and Control. Protocol for case detection, laboratory diagnosis and environmental testing of Mycobacterium chimaera infections potentially associated with heater–cooler units. (Available at:)http://ecdc.europa.eu/en/activities/diseaseprogrammes/ARHAI/Pages/about_programme.aspxEU. ([last accessed October 2019]) Google ScholarSee all References64]. | IIa | C |
HCD, heater–cooler device; OR, operating room; ECDC, European Centre for Disease Prevention and Control.
Google ScholarSee all References28].
Institutions should continue to follow updated manufacturer instructions for cleaning and disinfection of these devices [110x[110]Casini, B., Tuvo, B., Totaro, M., Baggiani, A., and Privitera, G. Detection and decontamination of Mycobacterium chimaera and other non-tuberculosis mycobacteria in heater–cooler devices used in cardiopulmonary bypass: a manufacturer and national guidelines summary, and a potential resolution to the problem requiring further investigation. Perfusion. 2019 Aug 30;
([Epub ahead of print])
Google ScholarSee all References110]. More recently, LivaNova issued updated instructions in the monitoring of hydrogen peroxide concentrations in the HCD water circuit [111x[111]Food and Drug Administration. Updated information to reduce potential cardiac surgery infection risks associated with the LivaNova 3T heater–cooler systems: FDA Safety Communication. ; October 19th, 2018
Google ScholarSee all References111]. The manufacturer also implemented device modifications consisting of a vacuum and sealing upgrade and an aerosol collection kit in 2017 [42x[42]LivaNova implements 3T heater–cooler device modification. (Available at:)https://investor.livanova.com/static-files/9cf37b42-8164-4eff-9820-7504e5dc3c1f; 2018. ([last accessed March 2019])
Google ScholarSee all References42]. Currently, we cannot make a statement with regard to the safety of these modifications due to a lack of data. Additionally, LivaNova offers a refurbishing and disinfection program of their 3T-HCD with replacement of accessories, tubing and connectors to prevent recontamination [34x[34]Garvey, M.I., Ashford, R., Bradley, C.W., Bradley, C.R., Martin, T.A., Walker, J. et al. Decontamination of heater–cooler units associated with contamination by atypical mycobacteria. J Hosp Infect. 2016;
93: 229–234
Google ScholarSee all References34]. However, there is no consistent evidence that M. chimaera can be eradicated from any HCD model once contaminated.
Some advocate routine microbiological screening of HCDs. However, there is no standardization with regard to the collection of samples and the laboratory methods used, with differences among environmental laboratories. In addition, the degree of device contamination required to generate positive HCD water and air cultures is unknown, thus the ultimate benefit is uncertain. Water samples of 1000 mL cultured in MGIT medium had the highest sensitivity for M. chimaera detection in a recent study [112x[112]Schreiber, P.W., Kohler, N., Cervera, R., Hasse, B., Sax, H., and Keller, P.M. Detection limit of Mycobacterium chimaera in water samples for monitoring medical device safety: insights from a pilot experimental series. J Hosp Infect. 2018;
99: 284–289
Google ScholarSee all References112]. Routine surveillance is not widely adopted due to slow growth of this organism in laboratory cultures, which can take up to eight weeks; this delay can lead to the use of contaminated machines during this prolonged incubation period [108x[108]Ogunremi, T., Taylor, G., Johnston, L., Amaratunga, K., Muller, M., Coady, A. et al. Mycobacterium chimaera infections in post-operative patients exposed to heater–cooler devices: an overview. Can Commun Dis Rep. 2017;
43: 107–113
Google ScholarSee all References108,112x[112]Schreiber, P.W., Kohler, N., Cervera, R., Hasse, B., Sax, H., and Keller, P.M. Detection limit of Mycobacterium chimaera in water samples for monitoring medical device safety: insights from a pilot experimental series. J Hosp Infect. 2018;
99: 284–289
Google ScholarSee all References112].
Additionally, sampling and testing protocols have not been validated, with some concern for false negative results.
Reporting of adverse events that occur as a result of medical device use is encouraged in most jurisdictions. Healthcare professionals should report cases of M. chimaera infection thought to be associated with use of a contaminated HCD to the respective regulatory authority [101x[101]Allen, K.B., Yuh, D.D., Schwartz, S.B., Lange, R.A., Hopkins, R., Bauer, K. et al. Nontuberculous Mycobacterium infections associated with heater–cooler devices. Ann Thorac Surg. 2017;
104: 1237–1242
Google ScholarSee all References101].
Areas of future research
As highlighted throughout this document, there are many aspects of diagnosis, management, and prevention that need further research. The results of subsequent investigations will not only be critical with regard to improved understanding of post-cardiovascular surgical M. chimaera infections, but will also help to gain insight into other types of mycobacterial infections acquired in the operative setting [113x[113]Diekema, D.J. Mycobacterium chimaera infections after cardiovascular surgery: lessons from a global outbreak. Trans Am Clin Climatol Assoc. 2019;
130: 136–144
Google ScholarSee all References113].
The extent of this outbreak and especially the risk to the paediatric population are undefined [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7,114x[114]Sargent, H.M., Crouch, G.C., Roberts, S., and Finucane, A.K. Prosthetic conduit endocarditis with nontuberculous mycobacteria in a child: associated with the water mattress and heater chiller unit. World J Pediatr Congenit Heart Surg. 2019 May 15;
([Epub ahead of print])
Google ScholarSee all References114]. Case-finding strategies, device safety alerts and microbiological diagnostics need improvements [107x[107]Mertz, D., Macri, J., Hota, S., Amaratunga, K., Davis, I., Johnston, L. et al. Response to alert on possible infections with Mycobacterium chimaera from contaminated heater–cooler devices in hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP). Infect Control Hosp Epidemiol. 2018;
39: 482–484
Google ScholarSee all References107]. Due to the rarity of the disease, the task force strongly encourages multicentre outcomes data collections to address key questions regarding optimal medical therapy, which is currently undefined. There are currently efforts to create a US registry of patients infected with NTM after exposure to HCDs during cardiac surgery, and the registry hopes to provide more details and guidance on the epidemiology, clinical manifestations, treatment, and outcomes for patients with related infections. Additional details regarding enrolling patients to the registry can be found at http://www.NTMInfect.org. The correlation between treatment response and in-vitro susceptibility of the isolates to anti-mycobacterial drugs needs further study. The role of therapeutic drug monitoring requires clarification as well [7x[7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015;
36: 2745–2753
Google ScholarSee all References7]. Collaborative discussions between medical device manufacturers, engineers and hospital epidemiology experts will be needed as new HCDs are designed. Additionally, reliable decontamination and identification of agents that can disrupt biofilms and increase chlorine susceptibility of mycobacteria are required [115x[115]Burgess, W., Margolis, A., Gibbs, S., Duarte, R.S., and Jackson, M. Disinfectant susceptibility profiling of glutaraldehyde-resistant nontuberculous mycobacteria. Infect Control Hosp Epidemiol. 2017;
38: 784–791
Google ScholarSee all References115]. Moreover, other mycobacteria [46x[46]Baker, A.W., Lewis, S.S., Alexander, B.D., Chen, L.F., Wallace, R.J. Jr., Brown-Elliott, B.A. et al. Two-phase hospital-associated outbreak of Mycobacterium abscessus: investigation and mitigation. Clin Infect Dis. 2017;
64: 902–911
Google ScholarSee all References46,112x[112]Schreiber, P.W., Kohler, N., Cervera, R., Hasse, B., Sax, H., and Keller, P.M. Detection limit of Mycobacterium chimaera in water samples for monitoring medical device safety: insights from a pilot experimental series. J Hosp Infect. 2018;
99: 284–289
Google ScholarSee all References112,116x[116]Nagpal, A., Wentink, J.E., Berbari, E.F., Aronhalt, K.C., Wright, A.J., Krageschmidt, D.A. et al. Cluster of Mycobacterium wolinskyi surgical site infections at an academic medical center. Infect Control Hosp Epidemiol. 2014;
35: 1169–1175
Google ScholarSee all References116] as well as fungi, Legionella spp., non-fermenters such as Pseudomonas aeruginosa, coagulase-negative staphylococci, Micrococcus spp. and Gram-positive rods can also colonize HCD [104x[104]Gotting, T., Klassen, S., Jonas, D., Benk, C., Serr, A., Wagner, D. et al. Heater–cooler units: contamination of crucial devices in cardiothoracic surgery. J Hosp Infect. 2016;
93: 223–228
Google ScholarSee all References104] although the clinical relevance of colonization of the HCD with one or more of these organisms is unclear [46x[46]Baker, A.W., Lewis, S.S., Alexander, B.D., Chen, L.F., Wallace, R.J. Jr., Brown-Elliott, B.A. et al. Two-phase hospital-associated outbreak of Mycobacterium abscessus: investigation and mitigation. Clin Infect Dis. 2017;
64: 902–911
Google ScholarSee all References46,116x[116]Nagpal, A., Wentink, J.E., Berbari, E.F., Aronhalt, K.C., Wright, A.J., Krageschmidt, D.A. et al. Cluster of Mycobacterium wolinskyi surgical site infections at an academic medical center. Infect Control Hosp Epidemiol. 2014;
35: 1169–1175
Google ScholarSee all References116].
Funding sources
There was no external funding source. B.H.'s work was supported by the Swiss National Science Foundation, grant number 32473B_163132/1 and 2. J.M.M. received a personal 80:20 research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–2019.
Conflict of interest statement
None declared.
Authors' contributions statement
BH, MH and PK wrote the first draft, and BH, JMM and BHo wrote the final version of the manuscript. All investigators contributed to review of papers, interpretation of the data, review of drafts and approval of the final guideline.
Appendix A.
ISCVID Executive Committee (in alphabetical order):
E. Athan (Infectious Diseases Department at Barwon Health, University of Melbourne and Deakin University, Australia); A. Bayer (Geffen School of Medicine at UCLA Senior Investigator – LA Biomedical Research Institute at Harbor – UCLA, Los Angeles, California, USA); B. Barsic (Department for Infectious Diseases, School of Medicine, University of Zagreb, Zagreb, Croatia); G.R. Corey (Duke University Medical Center, Hubert–Yeargan Center for Global Health, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA); V.H. Chu (Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA); D.T. Durack (Division of Infectious Diseases, Duke University Medical Center, Durham, North Carolina, USA); C. Querido Fortes (Division of Infectious Diseases, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil); V. Fowler (Departments of Medicine and Molecular Genetics & Microbiology, Duke University Medical Center, Durham, North Carolina, USA); B. Hoen (President; Department of Infectious Diseases and Tropical Medicine, University Medical Center of Nancy, Vandoeuvre Cedex, France); A. Waller Krachmer (Harvard Medical School, Boston, Massachusetts, Division of Infectious Diseases at the Beth Israel Deaconess Medical Center, Boston, USA); E. Durante-Magnoni (Infectious and Transplant Medicine of the ‘V. Monaldi’ teaching hospital in Naples, University of Campania ‘L. Vanvitelli’, Italy); J.M. Miro (Infectious Diseases at the Hospital Clinic – IDIBAPS, University of Barcelona, Barcelona, Spain); W.R. Wilson (Division of Infectious Diseases, Department of Internal Medicine, Mayo Clinic, College of Medicine and Science, Rochester, Minnesota, USA).
Infectious Diseases Specialists (in alphabetical order):
L.M. Baddour (Division of Infectious Diseases, Departments of Medicine and Cardiovascular Medicine, Mayo Clinic, College of Medicine and Science, Rochester, Minnesota, USA); D. Diekema (Division of Infectious Diseases, University of Iowa, Carver College of Medicine, Iowa, USA); N. Fernández-Hidalgo (Servei de Malalties Infeccioses, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain); S. Gordon (Department of Infectious Diseases, Cleveland Clinic, Ohio, USA); B. Hasse (Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland); J. Lundgren (Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark); V. Manfrin (Infectious and Tropical Diseases Department, San Bortolo Hospital, Vincenza, Italy); J. Nomura (Kaiser Permanente Infectious Diseases, Los Angeles, USA); J. Scriven (Liverpool School of Tropical Medicine, Liverpool, UK); R. Stewart (Monash Infectious Diseases, Monash Health, Melbourne, Australia); D. Wagner (Department of Internal Medicine II, Division of Infectious Diseases, Medical Center, University of Freiburg, Freiburg, Germany); T. Hing-Cheung Tang (Division of Infectious Diseases, Department of Medicine, Queen Elizabeth Hospital, University of Hong Kong, Hong Kong, China).
Hospital epidemiologists (in alphabetical order):
L.A. Herwaldt (Infectious Disease, University of Iowa, Iowa City, Iowa, USA); D. Mertz (Departments of Medicine, Health Research Methods, Evidence and Impact, and Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada); H. Sax (Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Switzerland); P. Schreiber (Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zurich, Switzerland); R. Sommerstein (Department of Infectious Diseases, Bern University Hospital, Bern, Switzerland); A. Stewardson (Department of Infectious Diseases Monash University, Australia); C.J. Whitener (Penn State Health, Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA); A. Widmer (Division of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Basel, Switzerland).
Microbiologists and molecular typing specialists (in alphabetical order):
B.A. Brown Elliot (Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA); C. Daley (Division of Mycobacterial and Respiratory Infections, National Jewish Health, Denver, Colorado, USA); T. Freiberger (Centre for Cardiovascular Surgery and Transplantation, Brno, and Faculty of Medicine, Masaryk University, Brno, Czech Republic); J. van Ingen (Department of Medical Microbiology, Radboud University Medical Centre, Nijmegen, The Netherlands); P. Keller (Institute of Medical Microbiology, University of Zurich, Zurich, Switzerland; Institute for Infectious Diseases, University of Bern, Bern, Switzerland); T.A. Kohl (Molecular and Experimental Mycobacteriology Group, Research Center, Borstel, Germany); F. Maurer (Diagnostic Mycobacteriology Group, National and WHO Supranational Reference Center for Mycobacteria, Research Center, Borstel, Germany); S. Niemann (Molecular and Experimental Mycobacteriology Group, Research Center, Borstel, Germany; German Center for Infection Research (DZIF), partner site Hamburg–Lübeck–Borstel–Riems, Borstel, Germany); R.J. Wallace Jr (Department of Microbiology, The University of Texas Health Science Center at Tyler, Tyler, Texas, USA).
Cardiac surgeons/perfusionists/cardiologists (in alphabetical order):
V. Falk (Heart Center, Charité; Berlin, Germany); M. Halbe (Clinic for Cardiovascular Surgery, University Hospital of Zurich, Zurich, Switzerland); C.A. Mestres (Clinic for Cardiovascular Surgery, University Hospital of Zurich, Zurich, Switzerland).
Ophthalmology:
S. Zweifel (Ophthalmology Unit, University of Zurich, Zurich, Switzerland).
Anaesthesiologists (in alphabetical order):
D. Bettex (Institute of Anaesthesiology, University Hospital Zurich, Zurich, Switzerland); A. Hernandez Conte (Department of Anaesthesiology, Kaiser Permanente, Los Angeles Medical Center, Los Angeles, California, USA).
Public Health (in alphabetical order):
M. Chand (National Infection Service, Public Health England, London, UK; Guy’s and St Thomas’ NHS Foundation Trust, Imperial College London, London, UK); M.C. Jarashow (Acute Communicable Disease Control, Los Angeles Department of Public Health, Los Angeles, California, USA); T. Lamagni (National Infection Service, Public Health England, London, UK); D. Plachouras (European Centre for Disease Prevention and Control, Solna, Sweden); K.M. Perkins (Centers for Disease Control and Prevention, Atlanta, Georgia, USA).
References
- [1]Tortoli, E., Rindi, L., Garcia, M.J., Chiaradonna, P., Dei, R., Garzelli, C. et al. Proposal to elevate the genetic variant MAC-A, included in the Mycobacterium avium complex, to species rank as Mycobacterium chimaera sp. nov. Int J Syst Evol Microbiol. 2004; 54: 1277–1285
- [2]Schweickert, B., Goldenberg, O., Richter, E., Gobel, U.B., Petrich, A., Buchholz, P. et al. Occurrence and clinical relevance of Mycobacterium chimaera sp. nov., Germany. Emerg Infect Dis. 2008; 14: 1443–1446
- [3]Achermann, Y., Rossle, M., Hoffmann, M., Deggim, V., Kuster, S., Zimmermann, D.R. et al. Prosthetic valve endocarditis and bloodstream infection due to Mycobacterium chimaera. J Clin Microbiol. 2013; 51: 1769–1773
- [4]Sax, H., Bloemberg, G., Hasse, B., Sommerstein, R., Kohler, P., Achermann, Y. et al. Prolonged outbreak of Mycobacterium chimaera infection after open-chest heart surgery. Clin Infect Dis. 2015; 61: 67–75
- [5]Zweifel, S.A., Mihic-Probst, D., Curcio, C.A., Barthelmes, D., Thielken, A., Keller, P.M. et al. Clinical and histopathologic ocular findings in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Ophthalmology. 2017; 124: 178–188
- [6]Kuehl, R., Banderet, F., Egli, A., Keller, P.M., Frei, R., Dobele, T. et al. Different types of heater–cooler units and their risk of transmission of Mycobacterium chimaera during open-heart surgery: clues from device design. Infect Control Hosp Epidemiol. 2018; 39: 834–840
- [7]Kohler, P., Kuster, S.P., Bloemberg, G., Schulthess, B., Frank, M., Tanner, F.C. et al. Healthcare-associated prosthetic heart valve, aortic vascular graft, and disseminated Mycobacterium chimaera infections subsequent to open heart surgery. Eur Heart J. 2015; 36: 2745–2753
- [8]Chand, M., Lamagni, T., Kranzer, K., Hedge, J., Moore, G., Parks, S. et al. Insidious risk of severe Mycobacterium chimaera infection in cardiac surgery patients. Clin Infect Dis. 2017; 64: 335–342
- [9]Scriven, J.E., Scobie, A., Verlander, N.Q., Houston, A., Collyns, T., Cajic, V. et al. Mycobacterium chimaera infection following cardiac surgery in the United Kingdom: clinical features and outcome of the first 30 cases. Clin Microbiol Infect. 2018; 24: 1164–1170
- [10]Chiesi, S., Piacentini, D., Salerno, N.D., Luise, D., Peracchi, M., Concia, E. et al. Disseminated Mycobacterium chimaera infection after open heart surgery in an Italian woman: a case report and a review of the literature. Infez Med. 2017; 25: 267–269
- [11]Cappabianca, G., Paparella, D., D’Onofrio, A., Caprili, L., Minniti, G., Lanzafame, M. et al. Mycobacterium chimaera infections following cardiac surgery in Italy: results from a National Survey Endorsed by the Italian Society of Cardiac Surgery. J Cardiovasc Med (Hagerstown). 2018; 19: 748–755
- [12]Gasch, O., Meije, Y., Espasa, M., Font, B., Jimenez, S., and Fernandez-Hidalgo, N. Disseminated infection due to Mycobacterium chimaera after aortic valve replacement. Rev Esp Cardiol (Engl Ed). 2019; 72: 502–503
- [13]Appenheimer, A. Mycobacterium chimaera outbreak response: experience from four US healthcare systems (Abstrct 2391). ID Week 2016, New Orleans, LA. (Available at:) ([last accessed April 2017]); October 29th 2016
- [14]Lyman, M.M., Grigg, C., Kinsey, C.B., Keckler, M.S., Moulton-Meissner, H., Cooper, E. et al. Invasive nontuberculous mycobacterial infections among cardiothoracic surgical patients exposed to heater–cooler devices. Emerg Infect Dis. 2017; 23: 796–805
- [15]Tan, N., Sampath, R., Abu Saleh, O.M., Tweet, M.S., Jevremovic, D., Alniemi, S. et al. Disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Open Forum Infect Dis. 2016; 3: ofw131
- [16]Oda, G., Ryono, R., Lucero-Obusan, C., Schirmer, P., Shanawani, H., Jacobs, K. et al. Epidemiologic review of veterans health administration patients with isolation of nontuberculous mycobacteria after cardiopulmonary bypass procedures. Infect Control Hosp Epidemiol. 2017; 38: 1103–1106
- [17]Rudikoff, A.G., Ganocy, T.K., Kansagra, K., Torres, F.A., Humphries, B.D., and Hernandez Conte, A. Thoracolumbar osteomyelitis secondary to systemic Mycobacterium chimaera infection status post aortic valve replacement. J Cardiothoracic Vasc Anesth. 2019; 33: 1704–1709
- [18]Shafizadeh, N., Hale, G., Bhatnagar, J., Alshak, N.S., and Nomura, J. Mycobacterium chimaera hepatitis: a new disease entity. Am J Surg Pathol. 2019; 43: 244–250
- [19]Balsam, L.B., Louie, E., Hill, F., Levine, J., and Phillips, M.S. Mycobacterium chimaera left ventricular assist device infections. J Card Surg. 2017; 32: 402–404
- [20]Cai, Y., Landolfo, K., and Renew, J.R. Mycobacterium infection from a cardiopulmonary bypass heater–cooler unit in a patient with steroid-induced immunosuppression. Can J Anaesth. 2017; 64: 513–516
- [21]Hamad, R., Noly, P.E., Perrault, L.P., Pellerin, M., and Demers, P. Mycobacterium chimaera infection after cardiac surgery: first Canadian outbreak. (e43–e5)Ann Thorac Surg. 2017; 104
- [22]O’Neil, C.R., Taylor, G., Smith, S., Joffe, A.M., Antonation, K., Shafran, S. et al. Mycobacterium chimaera infection after aortic valve replacement presenting with aortic dissection and pseudoaneurysm. Open Forum Infect Dis. 2018; 5: ofy018
- [23]Stewardson, A.J., Stuart, R.L., Cheng, A.C., and Johnson, P.D. Mycobacterium chimaera and cardiac surgery. Med J Aust. 2017; 206: 132–135
- [24]Overton, K., Mennon, V., Mothobi, N., Neild, B., Martinez, E., Masters, J. et al. Cluster of invasive Mycobacteria chimaera infections following cardiac surgery demonstrating novel clinical features and risks of aortic valve replacement. Intern Med J. 2018; 48: 1514–1520
- [25]Zhang, X., Lin, J., Feng, Y., Wang, X., McNally, A., and Zong, Z. Identification of Mycobacterium chimaera in heater–cooler units in China. Sci Rep. 2018; 8: 7843
- [26]Perkins, K.M., Lawsin, A., Hasan, N.A., Strong, M., Halpin, A.L., Rodger, R.R. et al. Notes from the field: Mycobacterium chimaera contamination of heater–cooler devices used in cardiac surgery – United States. Morb Mortal Wkly Rep. 2016; 65: 1117–1118
- [27]Williamson, D., Howden, B., and Stinear, T. Mycobacterium chimaera spread from heating and cooling units in heart surgery. New Engl J Med. 2017; 376: 600–602
- [28]van Ingen, J., Kohl, T.A., Kranzer, K., Hasse, B., Keller, P.M., Katarzyna Szafranska, A. et al. Global outbreak of severe Mycobacterium chimaera disease after cardiac surgery: a molecular epidemiological study. Lancet Infect Dis. 2017; 17: 1033–1041
- [29]Ganatra, S., Sharma, A., D’Agostino, R., Gage, T., and Kinnunen, P. Mycobacterium chimaera mimicking sarcoidosis. Methodist Debakey Cardiovasc J. 2018; 14: 301–302
- [30]Haller, S., Holler, C., Jacobshagen, A., Hamouda, O., Abu Sin, M., Monnet, D.L. et al. Contamination during production of heater–cooler units by Mycobacterium chimaera potential cause for invasive cardiovascular infections: results of an outbreak investigation in Germany, April 2015 to February 2016. Euro Surveill. 2016; 21
- [31]Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F. et al. 2015 ESC Guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). Eur Heart J. 2015; 36: 3075–3128
- [32]Sommerstein, R., Hasse, B., Marschall, J., Sax, H., Genoni, M., Schlegel, M. et al. Global health estimate of invasive Mycobacterium chimaera infections associated with heater–cooler devices in cardiac surgery. Emerg Infect Dis. 2018; 24: 576–578
- [33]Sommerstein, R., Schreiber, P.W., Diekema, D.J., Edmond, M.B., Hasse, B., Marschall, J. et al. Mycobacterium chimaera outbreak associated with heater–cooler devices: piecing the puzzle together. Infect Control Hosp Epidemiol. 2017; 38: 103–108
- [34]Garvey, M.I., Ashford, R., Bradley, C.W., Bradley, C.R., Martin, T.A., Walker, J. et al. Decontamination of heater–cooler units associated with contamination by atypical mycobacteria. J Hosp Infect. 2016; 93: 229–234
- [35]Sommerstein, R., Ruegg, C., Kohler, P., Bloemberg, G., Kuster, S.P., and Sax, H. Transmission of Mycobacterium chimaera from heater–cooler units during cardiac surgery despite an ultraclean air ventilation system. Emerg Infect Dis. 2016; 22: 1008–1013
- [36]Centers for Disease Control and Prevention. Non-tuberculous mycobacterium (NTM) infections and heater–cooler devices interim practical guidance. (Available at:) ([last accessed March 2016])CDC, Atlanta; October 2015
- [37]Svensson, E., Jensen, E.T., Rasmussen, E.M., Folkvardsen, D.B., Norman, A., and Lillebaek, T. Mycobacterium chimaera in heater–cooler units in denmark related to isolates from the United States and United Kingdom. Emerg Infect Dis. 2017; 23
- [38]Lande, L., Alexander, D.C., Wallace, R.J. Jr., Kwait, R., Iakhiaeva, E., Williams, M. et al. Mycobacterium avium in community and household water, suburban Philadelphia, Pennsylvania, USA, 2010–2012. Emerg Infect Dis. 2019; 25: 473–481
- [39]Kuehl, R., Banderet, F., Egli, A., Keller, P.M., Frei, R., Dobele, T. et al. Different types of heater–cooler units and their risk of transmission of Mycobacterium chimaera during open-heart surgery: clues from device design. Infect Control Hosp Epidemiol. 2018; 39: 834–840
- [40]Trudzinski, F.C., Schlotthauer, U., Kamp, A., Hennemann, K., Muellenbach, R.M., Reischl, U. et al. Clinical implications of Mycobacterium chimaera detection in thermoregulatory devices used for extracorporeal membrane oxygenation (ECMO), Germany, 2015 to 2016. Euro Surveill. 2016; : 21
- [41]Schreiber, P.W., Kuster, S.P., Hasse, B., Bayard, C., Ruegg, C., Kohler, P. et al. Reemergence of Mycobacterium chimaera in heater–cooler units despite intensified cleaning and disinfection protocol. Emerg Infect Dis. 2016; 22: 1830–1833
- [42]LivaNova implements 3T heater–cooler device modification. (Available at:) ([last accessed March 2019])
- [43]Stuckey, M., Christensen, B., and Moulton-Meissner, H. Out of thin air: assessing dispersion of Mycobacterium chimaera in the operating room. in: Abstract presented at: 67th Annual Epidemic Intelligence Service Conference, Atlanta, GA. ; April 17th, 2018
- [44]Walker, J.T., Lamagni, T., and Chand, M. Evidence that Mycobacterium chimaera aerosols penetrate laminar airflow and result in infections at the surgical field. Lancet Infect Dis. 2017; 17: 1019
- [45]Rosero, C.I. and Shams, W.E. Mycobacterium chimaera infection masquerading as a lung mass in a healthcare worker. IDCases. 2019; 15: e00526
- [46]Baker, A.W., Lewis, S.S., Alexander, B.D., Chen, L.F., Wallace, R.J. Jr., Brown-Elliott, B.A. et al. Two-phase hospital-associated outbreak of Mycobacterium abscessus: investigation and mitigation. Clin Infect Dis. 2017; 64: 902–911
- [47]Griffith, D.E., Aksamit, T., Brown-Elliott, B.A., Catanzaro, A., Daley, C., Gordin, F. et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Resp Crit Care Med. 2007; 175: 367–416
- [48]Hasse, B. SY0821. Clinical management of Mycobacterium chimaera infection. (Available at:) ([last accessed October 2019])ECCMID, Austria; 2017
- [49]Asadi, T., Mullin, K., Roselli, E., Johnston, D., Tan, C.D., Rodriguez, E.R. et al. Disseminated Mycobacterium chimaera infection associated with heater–cooler units after aortic valve surgery without endocarditis. J Thoracic Cardiovasc Surg. 2018; 155: 2369–2374
- [50]Schreiber, P.W., Hasse, B., and Sax, H. Mycobacterium chimaera infections after cardiac surgery – lessons learned. Clin Microbiol Infect. 2018; 24: 1117–1118
- [51]Lau, D., Cooper, R., Chen, J., Sim, V.L., McCombe, J.A., Tyrrell, G.J. et al. Mycobacterium chimaera encephalitis post-cardiac surgery: a new syndrome. ([Epub ahead of print])Clin Infect Dis. 2019 Jun 18;
- [52]Boni, C., Al-Sheikh, M., Hasse, B., Eberhard, R., Kohler, P., Hasler, P. et al. Multimodal imaging of choroidal lesions in disseminated Mycobacterium chimaera infection after cardiothoracic surgery. Retina. 2019; 39: 452–464
- [53]Brown, C.S., Smith, C.J., Breen, R.A., Ormerod, L.P., Mittal, R., Fisk, M. et al. Determinants of treatment-related paradoxical reactions during anti-tuberculosis therapy: a case control study. BMC Infect Dis. 2016; 16: 479
- [54]Phillips, P., Bonner, S., Gataric, N., Bai, T., Wilcox, P., Hogg, R. et al. Nontuberculous mycobacterial immune reconstitution syndrome in HIV-infected patients: spectrum of disease and long-term follow-up. Clin Infect Dis. 2005; 41: 1483–1497
- [55]Wilson, W.R., Bower, T.C., Creager, M.A., Amin-Hanjani, S., O’Gara, P.T., Lockhart, P.B. et al. Vascular graft infections, mycotic aneurysms, and endovascular infections: a scientific statement from the American Heart Association. (e412–e60)Circulation. 2016; 134
- [56]Sah, B.R., Husmann, L., Mayer, D., Scherrer, A., Rancic, Z., Puippe, G. et al. Diagnostic performance of 18F-FDG-PET/CT in vascular graft infections. Eur J Vasc Endovasc Surg. 2015; 49: 455–464
- [57]Roque, A., Pizzi, M.N., Cuellar-Calabria, H., and Aguade-Bruix, S. (18)F-FDG-PET/CT angiography for the diagnosis of infective endocarditis. Curr Cardiol Rep. 2017; 19: 15
- [58]Granados, U., Fuster, D., Pericas, J.M., Llopis, J.L., Ninot, S., Quintana, E. et al. Diagnostic accuracy of 18F-FDG PET/CT in infective endocarditis and implantable cardiac electronic device infection: a cross-sectional study. J Nucl Med. 2016; 57: 1726–1732
- [59]Orvin, K., Goldberg, E., Bernstine, H., Groshar, D., Sagie, A., Kornowski, R. et al. The role of FDG-PET/CT imaging in early detection of extra-cardiac complications of infective endocarditis. Clin Microbiol Infect. 2015; 21: 69–76
- [60]Husmann, L., Huellner, M.W., Ledergerber, B., Anagnostopoulos, A., Stolzmann, P., Sah, B.R. et al. Comparing diagnostic accuracy of 18F-FDG-PET/CT, contrast enhanced CT and combined imaging in patients with suspected vascular graft infections. Eur J Nucl Med Mol Imaging. 2019; 46: 1359–1368
- [61]Husmann, L., Ledergerber, B., Anagnostopoulos, A., Stolzmann, P., Sah, B.R., Burger, I.A. et al. The role of FDG PET/CT in therapy control of aortic graft infection. Eur J Nucl Med Mol Imaging. 2018; 45: 1987–1997
- [62]van Ingen, J. Microbiological diagnosis of nontuberculous mycobacterial pulmonary disease. Clin Chest Med. 2015; 36: 43–54
- [63]Inojosa, W.O., Minniti, G., and Scotton, P.G. Is Mycobacterium chimaera infection after cardiac surgery a risk factor for bacterial prosthetic valve endocarditis?. ([Epub ahead of print])Clin Infect Dis. 2019 Jun 20;
- [64]European Centre for Disease Prevention and Control. Protocol for case detection, laboratory diagnosis and environmental testing of Mycobacterium chimaera infections potentially associated with heater–cooler units. (Available at:) ([last accessed October 2019])
- [65]Wallace, R.J. Jr., Iakhiaeva, E., Williams, M.D., Brown-Elliott, B.A., Vasireddy, S., Vasireddy, R. et al. Absence of Mycobacterium intracellulare and presence of Mycobacterium chimaera in household water and biofilm samples of patients in the United States with Mycobacterium avium complex respiratory disease. J Clin Microbiol. 2013; 51: 1747–1752
- [66]Mok, S., Rogers, T.R., and Fitzgibbon, M. Evaluation of GenoType NTM-DR assay for identification of Mycobacterium chimaera. J Clin Microbiol. 2017; 55: 1821–1826
- [67]Lecorche, E., Haenn, S., Mougari, F., Kumanski, S., Veziris, N., Benmansour, H. et al. Comparison of methods available for identification of Mycobacterium chimaera. Clin Microbiol Infect. 2018; 24: 409–413
- [68]Epperson, L.E., Timke, M., Hasan, N.A., Godo, P., Durbin, D., Helstrom, N.K. et al. Evaluation of a novel MALDI biotyper algorithm to distinguish Mycobacterium intracellulare from Mycobacterium chimaera. Front Microbiol. 2018; 9: 3140
- [69]Zozaya-Valdes, E., Porter, J.L., Coventry, J., Fyfe, J.A., Carter, G.P., da Silva, A.G. et al. A target-specific assay for rapid and quantitative detection of Mycobacterium chimaera DNA. J Clin Microbiol. 2017; 55: 1847–1856
- [70]Hasan, N.A., Epperson, L.E., Lawsin, A., Rodger, R.R., Perkins, K.M., Halpin, A.L. et al. Genomic analysis of cardiac surgery-associated Mycobacterium chimaera infections, United States. Emerg Infect Dis. 2019; 25: 559–563
- [71]Nomura, J., Rieg, G., Bluestone, G., Townson Tsai, T., Lai, A., Dryjanski-Yanovsky, J. et al. Rapid detection of invasive Mycobacterium chimaera infection by using a novel plasma-based next-generation sequencing assay. Open Forum Infect Dis. 2017; 4: S174
- [72]Nomura, J., Rieg, G., Bluestone, G., Tsai, T., Lai, A., Terashita, D. et al. Rapid detection of invasive Mycobacterium chimaera disease via a novel plasma-based next-generation sequencing test. BMC Infect Dis. 2019; 19: 371
- [73]Chairs ASToIECGWC, Pettersson, G.B., Coselli, J.S., Writing, C., Pettersson, G.B., Coselli, J.S. et al. The American Association for Thoracic Surgery (AATS) consensus guidelines: surgical treatment of infective endocarditis: executive summary. (1241–1258 e29)J Thoracic Cardiovasc Surg 2017. 2016; 153
- [74]Deggim-Messmer, V., Bloemberg, G.V., Ritter, C., Voit, A., Homke, R., Keller, P.M. et al. Diagnostic molecular mycobacteriology in regions with low tuberculosis endemicity: combining real-time PCR assays for detection of multiple mycobacterial pathogens with line probe assays for identification of resistance mutations. EBioMedicine. 2016; 9: 228–237
- [75]Marchetti, G., Gori, A., Catozzi, L., Vago, L., Nebuloni, M., Rossi, M.C. et al. Evaluation of PCR in detection of Mycobacterium tuberculosis from formalin-fixed, paraffin-embedded tissues: comparison of four amplification assays. J Clin Microbiol. 1998; 36: 1512–1517
- [76]Zimmermann, D.R., Stadeli-Brodbeck, R., Ajmo, M., Dours-Zimmermann, M.T., Pfyffer, G.E., and Heitz, P.U. Molecular pathologic detection of mycobacteria. Verh Dtsch Ges Pathol. 1997; 81: 273–280
- [77]Koh, W.J., Jeong, B.H., Jeon, K., Lee, S.Y., and Shin, S.J. Therapeutic drug monitoring in the treatment of Mycobacterium avium complex lung disease. Am J Resp Crit Care Med. 2012; 186: 797–802
- [78]Morimoto, K., Namkoong, H., Hasegawa, N., Nakagawa, T., Morino, E., Shiraishi, Y. et al. Macrolide-resistant Mycobacterium avium complex lung disease: analysis of 102 consecutive cases. Ann Am Thorac Soc. 2016; 13: 1904–1911
- [79]Brown-Elliott, B.A., Nash, K.A., and Wallace, R.J. Jr. Antimicrobial susceptibility testing, drug resistance mechanisms, and therapy of infections with nontuberculous mycobacteria. Clin Microbiol Rev. 2012; 25: 545–582
- [80]van Ingen, J., Totten, S.E., Helstrom, N.K., Heifets, L.B., Boeree, M.J., and Daley, C.L. In vitro synergy between clofazimine and amikacin in treatment of nontuberculous mycobacterial disease. Antimicrob Agents Chemother. 2012; 56: 6324–6327
- [81]Koh, W.J., Hong, G., Kim, S.Y., Jeong, B.H., Park, H.Y., Jeon, K. et al. Treatment of refractory Mycobacterium avium complex lung disease with a moxifloxacin-containing regimen. Antimicrob Agents Chemother. 2013; 57: 2281–2285
- [82]Maurer, F.P., Pohle, P., Kernbach, M., Sievert, D., Hillemann, D., Rupp, J. et al. Differential drug susceptibility patterns of Mycobacterium chimaera and other members of the Mycobacterium avium–intracellulare complex. (379.e1–379.e7)Clin Microbiol Infect. 2019; 25
- [83]Ruth, M.M., Sangen, J.J.N., Remmers, K., Pennings, L.J., Svensson, E., Aarnoutse, R.E. et al. A bedaquiline/clofazimine combination regimen might add activity to the treatment of clinically relevant non-tuberculous mycobacteria. J Antimicrob Chemother. 2019; 74: 935–943
- [84]Philley, J.V., Wallace, R.J. Jr., Benwill, J.L., Taskar, V., Brown-Elliott, B.A., Thakkar, F. et al. Preliminary results of bedaquiline as salvage therapy for patients with nontuberculous mycobacterial lung disease. Chest. 2015; 148: 499–506
- [85]Martin, A., Godino, I.T., Aguilar-Ayala, D.A., Mathys, V., Lounis, N., and Villalobos, H.R. In vitro activity of bedaquiline against slow-growing nontuberculous mycobacteria. J Med Microbiol. 2019; 68: 1137–1139
- [86]Griffith, D.E., Brown-Elliott, B.A., Shepherd, S., McLarty, J., Griffith, L., and Wallace, R.J. Jr. Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease. Am J Resp Crit Care Med. 2005; 172: 250–253
- [87]Magis-Escurra, C., Alffenaar, J.W., Hoefnagels, I., Dekhuijzen, P.N., Boeree, M.J., van Ingen, J. et al. Pharmacokinetic studies in patients with nontuberculous mycobacterial lung infections. Int J Antimicrob Agents. 2013; 42: 256–261
- [88]van Ingen, J., Egelund, E.F., Levin, A., Totten, S.E., Boeree, M.J., Mouton, J.W. et al. The pharmacokinetics and pharmacodynamics of pulmonary Mycobacterium avium complex disease treatment. Am J Resp Crit Care Med. 2012; 186: 559–565
- [89]Jeong, B.H., Jeon, K., Park, H.Y., Moon, S.M., Kim, S.Y., Lee, S.Y. et al. Peak plasma concentration of azithromycin and treatment responses in Mycobacterium avium complex lung disease. Antimicrob Agents Chemother. 2016; 60: 6076–6083
- [90]Woods, G.L. Susceptibility testing of mycobacteria, Nocardia spp., and other aerobic actinomycetes. (CLSI document M24Ed3)3rd edition. Clinical and Laboratory Standards Institute, Wayne, PA; 2018
- [91]Woods, G.L. Performance standards for susceptibility testing of mycobacteria, nocardia spp. and other aerobic actinomycetes. CLSI doument M62Ed1. Clinical and Laboratory Standards Institute, Wayne, PA; 2018
- [92]Nikolayevskyy, V., Maurer, F.P., Holicka, Y., Taylor, L., Liddy, H., and Kranzer, K. Novel external quality assurance scheme for drug susceptibility testing of non-tuberculous mycobacteria: a multicentre pilot study. J Antimicrob Chemother. 2019; 74: 1288–1294
- [93]Woods, G.L. Susceptibility testing of mycobacteria, nocardia, and other aerobic actinomycetes; approved standard. CLSI document M24-A2. Clinical and Laboratory Standards Institute, Wayne, PA; 2011
- [94]Woods, G.L. Susceptibility testing of mycobacteria, nocardia and other aerobic actinomycetes; approved standard. NCCLS document M24-A. National Committee for Clinical Laboratory Standards, Wayne, PA; 2003
- [95]Mok, S., Hannan, M.M., Nolke, L., Stapleton, P., O’Sullivan, N., Murphy, P. et al. Antimicrobial susceptibility of clinical and environmental Mycobacterium chimaera Isolates. Antimicrob Agents Chemother. 2019; 63
- [96]Brown-Elliott, B.A., Iakhiaeva, E., Griffith, D.E., Woods, G.L., Stout, J.E., Wolfe, C.R. et al. In vitro activity of amikacin against isolates of Mycobacterium avium complex with proposed MIC breakpoints and finding of a 16S rRNA gene mutation in treated isolates. J Clin Microbiol. 2013; 51: 3389–3394
- [97]Bratzler, D.W., Dellinger, E.P., Olsen, K.M., Perl, T.M., Auwaerter, P.G., Bolon, M.K. et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013; 70: 195–283
- [98]Jarashow, M.C., Terashita, D., Balter, S., and Schwartz, B. Notes from the field: Mycobacteria chimaera infections associated with heater–cooler unit use during cardiopulmonary bypass surgery – Los Angeles County, 2012–2016. Morb Mortal Wkly Rep. 2019; 67: 1428–1429
- [99]Centers for Disease Control and Prevention. CDC advises hospitals to alert patients at risk from contaminated heater–cooler devices used during cardiac surgery. ; October 13th, 2016
- [100]Marra, A.R., Diekema, D.J., and Edmond, M.B. Mycobacterium chimaera infections associated with contaminated heater–cooler devices for cardiac surgery: outbreak management. Clin Infect Dis. 2017; 65: 669–674
- [101]Allen, K.B., Yuh, D.D., Schwartz, S.B., Lange, R.A., Hopkins, R., Bauer, K. et al. Nontuberculous Mycobacterium infections associated with heater–cooler devices. Ann Thorac Surg. 2017; 104: 1237–1242
- [102]Barker, T.A., Dandekar, U., Fraser, N., Dawkin, L., Sweeney, P., Heron, F. et al. Minimising the risk of Mycobacterium chimaera infection during cardiopulmonary bypass by the removal of heater–cooler units from the operating room. Perfusion. 2018; 33: 264–269
- [103]Percival, S.L., Suleman, L., Vuotto, C., and Donelli, G. Healthcare-associated infections, medical devices and biofilms: risk, tolerance and control. J Med Microbiol. 2015; 64: 323–334
- [104]Gotting, T., Klassen, S., Jonas, D., Benk, C., Serr, A., Wagner, D. et al. Heater–cooler units: contamination of crucial devices in cardiothoracic surgery. J Hosp Infect. 2016; 93: 223–228
- [105]Walker, J., Moore, G., Collins, S., Parks, S., Garvey, M.I., Lamagni, T. et al. Microbiological problems and biofilms associated with Mycobacterium chimaera in heater–cooler units used for cardiopulmonary bypass. J Hosp Infect. 2017; 96: 209–220
- [106]Garvey, M.I., Bradley, C.W., and Walker, J. A year in the life of a contaminated heater–cooler unit with Mycobacterium chimaera?. Infect control hosp epidemiol. 2017; 38: 705–711
- [107]Mertz, D., Macri, J., Hota, S., Amaratunga, K., Davis, I., Johnston, L. et al. Response to alert on possible infections with Mycobacterium chimaera from contaminated heater–cooler devices in hospitals participating in the Canadian Nosocomial Infection Surveillance Program (CNISP). Infect Control Hosp Epidemiol. 2018; 39: 482–484
- [108]Ogunremi, T., Taylor, G., Johnston, L., Amaratunga, K., Muller, M., Coady, A. et al. Mycobacterium chimaera infections in post-operative patients exposed to heater–cooler devices: an overview. Can Commun Dis Rep. 2017; 43: 107–113
- [109]Food and Drug Administration. Update: availability of deep-cleaning service of certain LivaNova PLC (formerly Sorin Group Deutschland GmbH) Stӧckert 3T heater–cooler systems in the U.S.:. (Available at:) ([last accessed March 2019])FDA Safety Communication, ; 2018
- [110]Casini, B., Tuvo, B., Totaro, M., Baggiani, A., and Privitera, G. Detection and decontamination of Mycobacterium chimaera and other non-tuberculosis mycobacteria in heater–cooler devices used in cardiopulmonary bypass: a manufacturer and national guidelines summary, and a potential resolution to the problem requiring further investigation. ([Epub ahead of print])Perfusion. 2019 Aug 30;
- [111]Food and Drug Administration. Updated information to reduce potential cardiac surgery infection risks associated with the LivaNova 3T heater–cooler systems: FDA Safety Communication. ; October 19th, 2018
- [112]Schreiber, P.W., Kohler, N., Cervera, R., Hasse, B., Sax, H., and Keller, P.M. Detection limit of Mycobacterium chimaera in water samples for monitoring medical device safety: insights from a pilot experimental series. J Hosp Infect. 2018; 99: 284–289
- [113]Diekema, D.J. Mycobacterium chimaera infections after cardiovascular surgery: lessons from a global outbreak. Trans Am Clin Climatol Assoc. 2019; 130: 136–144
- [114]Sargent, H.M., Crouch, G.C., Roberts, S., and Finucane, A.K. Prosthetic conduit endocarditis with nontuberculous mycobacteria in a child: associated with the water mattress and heater chiller unit. ([Epub ahead of print])World J Pediatr Congenit Heart Surg. 2019 May 15;
- [115]Burgess, W., Margolis, A., Gibbs, S., Duarte, R.S., and Jackson, M. Disinfectant susceptibility profiling of glutaraldehyde-resistant nontuberculous mycobacteria. Infect Control Hosp Epidemiol. 2017; 38: 784–791
- [116]Nagpal, A., Wentink, J.E., Berbari, E.F., Aronhalt, K.C., Wright, A.J., Krageschmidt, D.A. et al. Cluster of Mycobacterium wolinskyi surgical site infections at an academic medical center. Infect Control Hosp Epidemiol. 2014; 35: 1169–1175
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