Research Article| Volume 101, ISSUE 3, P339-346, March 2019

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Healthcare burden of probable and proven invasive mucormycosis: a multi-centre cost-of-illness analysis of patients treated in tertiary care hospitals between 2003 and 2016

Published:November 10, 2018DOI:



      Invasive mucormycosis (IM) is a rare invasive fungal infection with a high mortality rate. However, data concerning the clinical and economic burden of IM are scarce.


      To evaluate the direct treatment costs and additional expenditures of patients with IM.


      A retrospective cost-of-illness analysis of cases with IM extracted from FungiScope – Global Registry for Emerging Fungal Infections, accessible through the epidemiological research platform, was undertaken. Results of patients with IM were compared with those of matched patients with similar underlying conditions based on the German Diagnosis Related Group (G-DRG) coding.


      Out of 46 patients with probable/proven IM, 31 (67%) patients were male and the median age was 53 years (range 11–88 years). Forty-two patients (92%) had haematological diseases as the most common risk factor. Analysis of cost factors identified antifungal treatment due to IM as the primary cost driver [€22,816, 95% confidence interval (CI) €15,036–32,346], with mean overall direct treatment costs of €53,261 (95% CI €39,660–68,825). Compared with matched patients, patients with IM were treated in hospital for 26.5 additional days (standard deviation 31.8 days; P < 0.001), resulting in mean additional costs of €32,991 (95% CI €21,558–46,613; P < 0.001). Probable IM, as well as absence of chemotherapy, surgical measures due to IM, and antifungal prophylaxis were associated with lower overall costs. Nineteen patients (41.3%) died during hospitalization.


      This study demonstrates the considerable healthcare burden of IM. The choice of antifungal agent for treatment of IM had no impact on overall cost.


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        • European Medicines Agency
        Isavuconazonium sulfate for the treatment of mucormycosis.
        European Medicines Agency, London2014 (Available at: [last accessed 1 March 2018])
        • Bitar D.
        • Van Cauteren D.
        • Lanternier F.
        • Dannaoui E.
        • Che D.
        • Dromer F.
        • et al.
        Increasing incidence of zygomycosis (mucormycosis), France, 1997–2006.
        Emerg Infect Dis. 2009; 15: 1395-1401
        • Saegeman V.
        • Maertens J.
        • Meersseman W.
        • Spriet I.
        • Verbeken E.
        • Lagrou K.
        Increasing incidence of mucormycosis in University Hospital, Belgium.
        Emerg Infect Dis. 2010; 16: 1456-1458
        • Roden M.M.
        • Zaoutis T.E.
        • Buchanan W.L.
        • Knudsen T.A.
        • Sarkisova T.A.
        • Schaufele R.L.
        • et al.
        Epidemiology and outcome of zygomycosis: a review of 929 reported cases.
        Clin Infect Dis. 2005; 41: 634-653
        • Kontoyiannis D.P.
        • Marr K.A.
        • Park B.J.
        • Alexander B.D.
        • Anaissie E.J.
        • Walsh T.J.
        • et al.
        Prospective surveillance for invasive fungal infections in hematopoietic stem cell transplant recipients, 2001–2006: overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database.
        Clin Infect Dis. 2010; 50: 1091-1100
        • Skiada A.
        • Pagano L.
        • Groll A.
        • Zimmerli S.
        • Duppont B.
        • Lagrou K.
        • et al.
        Zygomycosis in Europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007.
        Clin Microbiol Infect. 2011; 17: 1859-1867
        • Chamilos G.
        • Lewis R.E.
        • Kontoyiannis D.P.
        Delaying amphotericin B-based frontline therapy significantly increases mortality among patients with hematologic malignancy who have zygomycosis.
        Clin Infect Dis. 2008; 47: 503-509
        • Cornely O.A.
        • Arikan-Akdagli S.
        • Dannaoui E.
        • Groll A.H.
        • Lagrou K.
        • Chakrabarti A.
        • et al.
        ESCMID and ECMM joint clinical guidelines for the diagnosis and management of mucormycosis 2013.
        Clin Microbiol Infect. 2014; 20: 5-26
        • Marty F.M.
        • Ostrosky-Zeichner L.
        • Cornely O.A.
        • Mullane K.M.
        • Perfect J.R.
        • Thompson 3rd, G.R.
        • et al.
        Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case–control analysis.
        Lancet Infect Dis. 2016; 16: 828-837
        • Vironneau P.
        • Kania R.
        • Morizot G.
        • Elie C.
        • Garcia-Hermoso D.
        • Herman P.
        • et al.
        Local control of rhino-orbito-cerebral mucormycosis dramatically impacts survival.
        Clin Microbiol Infect. 2014; 20: O336-O339
        • Zilberberg M.D.
        • Shorr A.F.
        • Huang H.
        • Chaudhari P.
        • Paly V.F.
        • Menzin J.
        Hospital days, hospitalization costs, and inpatient mortality among patients with mucormycosis: a retrospective analysis of US hospital discharge data.
        BMC Infect Dis. 2014; 14: 310
        • Menzin J.
        • Meyers J.L.
        • Friedman M.
        • Perfect J.R.
        • Langston A.A.
        • Danna R.P.
        • et al.
        Mortality, length of hospitalization, and costs associated with invasive fungal infections in high-risk patients.
        Am J Health Syst Pharm. 2009; 66: 1711-1717
        • Kontoyiannis D.P.
        • Yang H.
        • Song J.
        • Kelkar S.S.
        • Yang X.
        • Azie N.
        • et al.
        Prevalence, clinical and economic burden of mucormycosis-related hospitalizations in the United States: a retrospective study.
        BMC Infect Dis. 2016; 16: 730
        • De Pauw B.
        • Walsh T.J.
        • Donnelly J.P.
        • Stevens D.A.
        • Edwards J.E.
        • Calandra T.
        • et al.
        Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group.
        Clin Infect Dis. 2008; 46: 1813-1821
        • Seidel D.
        • Duran Graeff L.A.
        • Vehreschild M.
        • Wisplinghoff H.
        • Ziegler M.
        • Vehreschild J.J.
        • et al.
        FungiScope – Global Emerging Fungal Infection Registry.
        Mycoses. 2017; 60: 508-516
        • Ruping M.J.
        • Heinz W.J.
        • Kindo A.J.
        • Rickerts V.
        • Lass-Flörl C.
        • Beisel C.
        • et al.
        Forty-one recent cases of invasive zygomycosis from a global clinical registry.
        J Antimicrob Chemother. 2010; 65: 296-302
        • Pagano L.
        • Cornely O.A.
        • Busca A.
        • Caira M.
        • Cesaro S.
        • Gasbarrino C.
        • et al.
        Combined antifungal approach for the treatment of invasive mucormycosis in patients with hematologic diseases: a report from the SEIFEM and FUNGISCOPE registries.
        Haematologica. 2013; 98: e127-e130
        • Institute for Quality and Efficiency in Health Care
        General methods for health economic evaluation.
        Institute for Quality and Efficiency in Health Care, Cologne2015 (Available at:) ([last accessed 1 March 2018])
        • Graf von der Schulenburg J.M.
        • Greiner W.
        • Jost F.
        • Klusen N.
        • Kubin M.
        • Leidl R.
        • et al.
        German recommendations on health economic evaluation: third and updated version of the Hanover Consensus.
        Value Health. 2008; 11: 539-544
      1. Institute for the Hospital Remuration System – InEK GmbH, The G-DRG report-browser. Bonn. Available at:

        • Smith M.W.
        • Barnett P.G.
        • Phibbs C.S.
        • Wagner T.H.
        Microcosting methods for determining VA healthcare costs.
        Health Economics Resource Center, Menlo Park, CA2010
        • Hardin J.W.
        • Hilbe J.M.
        Generalized linear models and extensions.
        Stata Press, College Station, TX2018
        • Heimann S.M.
        • Cornely O.A.
        • Wisplinghoff H.
        • Kochanek M.
        • Stippel D.
        • Padosch S.A.
        • et al.
        Candidemia in the intensive care unit: analysis of direct treatment costs and clinical outcome in patients treated with echinocandins or fluconazole.
        Eur J Clin Microbiol Infect Dis. 2015; 34: 331-338
        • Rieger C.T.
        • Cornely O.A.
        • Hoppe-Tichy T.
        • Kiehl M.
        • Knoth H.
        • Thalheimer M.
        • et al.
        Treatment cost of invasive fungal disease (Ifd) in patients with acute myelogenous leukaemia (Aml) or myelodysplastic syndrome (Mds) in German hospitals.
        Mycoses. 2012; 55: 514-520
        • Maertens J.A.
        • Raad II,
        • Marr K.A.
        • Patterson T.F.
        • Kontoyiannis D.P.
        • Cornely O.A.
        • et al.
        Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial.
        Lancet. 2016; 387: 760-769
        • Cornely O.A.
        • Bohme A.
        • Schmitt-Hoffmann A.
        • Ullmann A.J.
        Safety and pharmacokinetics of isavuconazole as antifungal prophylaxis in acute myeloid leukemia patients with neutropenia: results of a phase 2, dose escalation study.
        Antimicrob Agents Chemother. 2015; 59: 2078-2085