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Impact of surgical site infection on healthcare costs and patient outcomes: a systematic review in six European countries

Open AccessPublished:March 08, 2017DOI:https://doi.org/10.1016/j.jhin.2017.03.004

      Summary

      Background

      Surgical site infections (SSIs) are associated with increased morbidity and mortality. Furthermore, SSIs constitute a financial burden and negatively impact on patient quality of life (QoL).

      Aim

      To assess, and evaluate the evidence for, the cost and health-related QoL (HRQoL) burden of SSIs across various surgical specialties in six European countries.

      Methods

      Electronic databases and conference proceedings were systematically searched to identify studies reporting the cost and HRQoL burden of SSIs. Studies published post 2005 in France, Germany, the Netherlands, Italy, Spain, and the UK were eligible for data extraction. Studies were categorized by surgical specialty, and the primary outcomes were the cost of infection, economic evaluations, and HRQoL.

      Findings

      Twenty-six studies met the eligibility criteria and were included for analysis. There was a paucity of evidence in the countries of interest; however, SSIs were consistently associated with elevated costs, relative to uninfected patients. Several studies reported that SSI patients required prolonged hospitalization, reoperation, readmission, and that SSIs increased mortality rates. Only one study reported QoL evidence, the results of which demonstrated that SSIs reduced HRQoL scores (EQ-5D). Hospitalization reportedly constituted a substantial cost burden, with additional costs arising from medical staff, investigation, and treatment costs.

      Conclusion

      Disparate reporting of SSIs makes direct cost comparisons difficult, but this review indicated that SSIs are extremely costly. Thus, rigorous procedures must be implemented to minimize SSIs. More economic and QoL studies are required to make accurate cost estimates and to understand the true burden of SSIs.

      Keywords

      Introduction

      Surgical site infection (SSI) is one of the most frequently reported types of hospital-acquired infection (HAI), constituting up to 19.6% of all HAIs in Europe in 2011–2012 [
      • European Centre for Disease Prevention and Control
      Point prevalence survey of healthcare associated infections and antimicrobial use in European acute care hospitals.
      ]. The Centre for Disease Control and Prevention (CDC) [and the European Centre for Disease Prevention and Control (ECDC)] defines SSI as postoperative infection occurring within 30 days of a surgical procedure (or within one year for permanent implants) [
      • European Centre for Disease Prevention and Control
      Surveillance of surgical site infections in Europe 2010–2011.
      ,
      • Culver D.H.
      • Horan T.C.
      • Gaynes R.P.
      • Martone W.J.
      • Jarvis W.R.
      • Emori T.G.
      • et al.
      Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infections Surveillance System.
      ,
      • Horan T.C.
      • Gaynes R.P.
      • Martone W.J.
      • Jarvis W.R.
      • Emori T.G.
      CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections.
      ].
      The development of an SSI causes a substantial increase in the clinical and economic burden of surgery. The financial burden of surgery is increased due to the direct costs incurred by prolonged hospitalization of the patient, diagnostic tests, and treatment. Certain patients may also require reoperation after the contraction of an SSI, which is associated with considerable additional costs [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ]. Indeed, Broex et al. demonstrated that in European hospitals patients who develop an SSI constitute a financial burden approximately double that of patients who do not develop an SSI [
      • Broex E.C.
      • van Asselt A.D.
      • Bruggeman C.A.
      • van Tiel F.H.
      Surgical site infections: how high are the costs?.
      ]. The same review also reported that the length of hospitalization was more than twice as long for patients with an SSI relative to uninfected patients [
      • Broex E.C.
      • van Asselt A.D.
      • Bruggeman C.A.
      • van Tiel F.H.
      Surgical site infections: how high are the costs?.
      ]. SSIs may therefore represent an opportunity cost to hospitals by displacing hospital resources that would otherwise be spent elsewhere, as well as delaying subsequent patients' surgery. Following discharge from hospital, SSI patients may also rely on healthcare from other community care services, which will further contribute to the economic burden of infection.
      SSIs negatively impact on patient physical and mental health. Increased patient morbidity, mortality, and loss of earnings during recovery are some of the indirect costs associated with infection. Intangible costs may also be incurred by the patient, such as pain and anxiety. In addition, patients may experience delayed wound healing and be more susceptible to secondary complications, such as bacteraemia [
      • Gottrup F.
      • Melling A.
      • Hollander D.A.
      An overview of surgical site infections: aetiology, incidence and risk factors.
      ,
      • Carnicer-Pont D.
      • Bailey K.
      • Mason B.
      • Walker A.
      • Evans M.
      • Salmon R.
      Risk factors for hospital-acquired methicillin-resistant Staphylococcus aureus bacteraemia: a case–control study.
      ]. Distress may also be caused to the patient and family members if the patient is absent from home and work for a prolonged period. Accordingly, prolonged hospitalization and increased morbidity as a result of developing an SSI have been shown to negatively impact on patient health-related quality of life (HRQoL) [
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ].
      There is limited evidence reporting the costs incurred following the development of an SSI, and few recent data comparing overall costs across surgical specialties. Thus, the aim of this systematic review was to assess, and evaluate the evidence for, the cost and HRQoL burden of SSI across various surgical specialties in Europe. The six countries included in the review were the ‘big five’ European nations (France, Germany, Italy, Spain, the UK), as well as the Netherlands.

      Methods

      The following electronic databases were interrogated on September 12th, 2015, to identify relevant studies: Embase, Medline, and the Cochrane Library. Supplementary data sources included reference lists of included publications and the following conference proceedings over the last three years’ availability: the International Society for Pharmacoeconomics and Outcomes Research (ISPOR), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the International Conference on Prevention and Infection Control (ICPIC), and the Healthcare Infection Society (HIS).
      National studies reporting SSI economic and/or quality of life (QoL) evidence in patients who underwent surgery in a hospital setting met the inclusion criteria. The review included studies published in English post 2005 that reported data for France, Germany, the Netherlands, Italy, Spain, and the UK. The population, interventions, comparators, outcomes, study design (PICOS) statement is summarized in Supplementary Appendix A. Titles and abstracts of publications yielded by the electronic searches were screened according to the eligibility criteria, and non-relevant studies were excluded. Full publications of potentially relevant publications were assessed by a single reviewer, and verified by a second reviewer. Eligible studies were represented multiple times if they reported on more than one European country or operation type. See the PRISMA flow diagram (Figure 1), which illustrates the number of eligible papers identified by the systematic review.
      Figure 1
      Figure 1Systematic review PRISMA flow diagram.
      Included studies were stratified by surgical specialty into the following groups: cardiothoracic surgery, general surgery, neurosurgery, orthopaedic and trauma surgery, otolaryngology, urology, and multiple or unspecified surgery.
      Economic evaluations (including cost–utility, cost-minimization, cost–effectiveness, and cost–benefit analyses) and studies reporting relevant cost of illness and/or QoL data were considered for inclusion. The primary outcomes of interest were direct and indirect healthcare costs, cost drivers, and proxy outcomes for which a cost could be applied such as length of stay (LOS), readmissions, the number of additional procedures required, and mortality. Both generic and condition-specific questionnaires describing the QoL associated with SSI and utilities derived from generic preference-based instruments (e.g. the EQ-5D) were of interest for the review. Quality assessment (QA) of cost of illness/burden studies were assessed by a checklist adapted to cost of illness (COI) by Molinier et al. [
      • Molinier L.
      • Bauvin E.
      • Combescure C.
      • Castelli C.
      • Rebillard X.
      • Soulié M.
      • et al.
      Methodological considerations in cost of prostate cancer studies: a systematic review.
      ].

      Results

      Search results

      A total of 9066 papers were identified via the electronic database searches. Upon the removal of duplicate papers, 7373 titles and abstracts were reviewed. A total of 360 potentially relevant publications were ordered for full paper review. Twenty-six studies were identified that reported costs and/or QoL associated with SSI; 24 were full publications and two were abstracts only (Figure 1) [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ,
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ,
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Defez C.
      • Fabbro-Peray P.
      • Cazaban M.
      • Boudemaghe T.
      • Sotto A.
      • Daures J.P.
      Additional direct medical costs of nosocomial infections: an estimation from a cohort of patients in a French university hospital.
      ,
      • Dhadwal K.
      • Al-Ruzzeh S.
      • Athanasiou T.
      • Choudhury M.
      • Tekkis P.
      • Vuddamalay P.
      • et al.
      Comparison of clinical and economic outcomes of two antibiotic prophylaxis regimens for sternal wound infection in high-risk patients following coronary artery bypass grafting surgery: a prospective randomised double-blind controlled trial.
      ,
      • Dholakia S.
      • Jeans J.P.
      • Khalid U.
      • Dholakia S.
      • D’Souza C.
      • Nemeth K.
      The association of noise and surgical-site infection in day-case hernia repairs.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ,
      • Hahnel J.
      • Burdekin H.
      • Anand S.
      Re-admissions following hip fracture surgery.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ,
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ,
      • Leaper D.
      • Nazir J.
      • Roberts C.
      • Searle R.
      Economic and clinical contributions of an antimicrobial barrier dressing: a strategy for the reduction of surgical site infections.
      ,
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ,
      • Nobile M.
      • Navone P.
      • Orzella A.
      • Colciago R.
      • Calori G.M.
      Developing a model for analysis the extra costs associated with surgical site infections (SSIs): an orthopaedic and traumatological study run by the Gaetano Pini Orthopaedic Institute.
      ,
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]. Countries from which the cost and QoL evidence was derived included France (N = 4), Germany (N = 2), Italy (N = 1), Spain (N = 3), and the UK (N = 16) [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ,
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ,
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Defez C.
      • Fabbro-Peray P.
      • Cazaban M.
      • Boudemaghe T.
      • Sotto A.
      • Daures J.P.
      Additional direct medical costs of nosocomial infections: an estimation from a cohort of patients in a French university hospital.
      ,
      • Dhadwal K.
      • Al-Ruzzeh S.
      • Athanasiou T.
      • Choudhury M.
      • Tekkis P.
      • Vuddamalay P.
      • et al.
      Comparison of clinical and economic outcomes of two antibiotic prophylaxis regimens for sternal wound infection in high-risk patients following coronary artery bypass grafting surgery: a prospective randomised double-blind controlled trial.
      ,
      • Dholakia S.
      • Jeans J.P.
      • Khalid U.
      • Dholakia S.
      • D’Souza C.
      • Nemeth K.
      The association of noise and surgical-site infection in day-case hernia repairs.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ,
      • Hahnel J.
      • Burdekin H.
      • Anand S.
      Re-admissions following hip fracture surgery.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ,
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ,
      • Leaper D.
      • Nazir J.
      • Roberts C.
      • Searle R.
      Economic and clinical contributions of an antimicrobial barrier dressing: a strategy for the reduction of surgical site infections.
      ,
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ,
      • Nobile M.
      • Navone P.
      • Orzella A.
      • Colciago R.
      • Calori G.M.
      Developing a model for analysis the extra costs associated with surgical site infections (SSIs): an orthopaedic and traumatological study run by the Gaetano Pini Orthopaedic Institute.
      ,
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]. The surgical specialties considered by the studies were cardiothoracic (N = 4), general (N = 3), neurosurgery (N = 2), orthopaedic and trauma (N = 7), otolaryngology (N = 1), and urology (N = 1) [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ,
      • Dholakia S.
      • Jeans J.P.
      • Khalid U.
      • Dholakia S.
      • D’Souza C.
      • Nemeth K.
      The association of noise and surgical-site infection in day-case hernia repairs.
      ,
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Dhadwal K.
      • Al-Ruzzeh S.
      • Athanasiou T.
      • Choudhury M.
      • Tekkis P.
      • Vuddamalay P.
      • et al.
      Comparison of clinical and economic outcomes of two antibiotic prophylaxis regimens for sternal wound infection in high-risk patients following coronary artery bypass grafting surgery: a prospective randomised double-blind controlled trial.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ,
      • Hahnel J.
      • Burdekin H.
      • Anand S.
      Re-admissions following hip fracture surgery.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ,
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ,
      • Nobile M.
      • Navone P.
      • Orzella A.
      • Colciago R.
      • Calori G.M.
      Developing a model for analysis the extra costs associated with surgical site infections (SSIs): an orthopaedic and traumatological study run by the Gaetano Pini Orthopaedic Institute.
      ,
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]. Seven studies considered multiple surgical specialties and one study did not specify the surgical specialty considered (Table I, Table II, Table III, Table IV, Table V) [
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ,
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Defez C.
      • Fabbro-Peray P.
      • Cazaban M.
      • Boudemaghe T.
      • Sotto A.
      • Daures J.P.
      Additional direct medical costs of nosocomial infections: an estimation from a cohort of patients in a French university hospital.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ,
      • Leaper D.
      • Nazir J.
      • Roberts C.
      • Searle R.
      Economic and clinical contributions of an antimicrobial barrier dressing: a strategy for the reduction of surgical site infections.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ].

      France

      Four full publication studies were identified for France [
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Defez C.
      • Fabbro-Peray P.
      • Cazaban M.
      • Boudemaghe T.
      • Sotto A.
      • Daures J.P.
      Additional direct medical costs of nosocomial infections: an estimation from a cohort of patients in a French university hospital.
      ,
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ,
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ]. Two studies were cost analyses and two studies were prospective cohort studies. The surgical specialties considered in the studies included cardiothoracic surgery (N = 1), otolaryngology surgery (N = 1), multiple surgical specialties (N = 1), and one study did not specify the surgical specialty. The outcomes reported included the study incidence of SSIs (N = 3), direct costs (N = 4), cost drivers (N = 2), LOS (N = 3), mortality (N = 2), and the requirement for additional procedures (N = 1) (Table I).
      Table IBurden of surgical site infection in France
      Study, publication type, study typeNo. of patientsEpidemiology results (incidence/prevalence)CostsProxy outcomes
      Cardiothoracic surgery (N = 1)
       Cossin et al.
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.


       Cost analysis study
      N = 8569
      • Rate of SSI:
        • Year 1 (2008): 52 (2.5%)
        • Year 2 (2009): 35 (1.9%)
        • Year 3 (2010): 45 (2.2%)
        • Year 4 (2011): 62 (2.3%)
      • Total additional cost of SSI over four years:
        • With reimbursement: €291,000 for 94 patients
        • Without reimbursement: €1,034,000 (patients NR)
      • Mean duration of post-surgery hospital stay (days):
        • SSI: 23
        • No SSI: 10 (P < 0.01)
      • Mortality during four-year study period:
        • SSI: 9 (5.4%)
        • No SSI: 205 (2.4%)
      Otolaryngology (N = 1)
       Penel et al.
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.


       Prospective cohort study
      N = 261
      • Incidence of SSI:
        • 94 (36%)
      • Total medical cost per patient (SD):
        • SSI: €39,957 (29,802)
        • No SSI: €22,523 (10,679)
      • Mean hospital LOS [days (SD)]:
        • SSI: 35.02 (26.12)
        • No SSI: 19.74 (9.36)
      Multiple or unspecified surgical specialties (N = 2)
       Defez et al.
      • Defez C.
      • Fabbro-Peray P.
      • Cazaban M.
      • Boudemaghe T.
      • Sotto A.
      • Daures J.P.
      Additional direct medical costs of nosocomial infections: an estimation from a cohort of patients in a French university hospital.


       Prospective cohort study
      N = 300 (SSI cases, n = 30; controls, n = 30)NRTotal additional cost per SSI patient by expenditure (SD): €1,814 (4,226)

      Total additional cost of SSI by site: €386,297
      NR
       Lamarsalle et al.
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.


       Cost analysis study
      NR: 520,715 surgical procedures were includedTotal incidence of SSI: 3.0%
      • Total additional cost associated with SSI following surgery in 2010:
        • Public hospitals: €43,019,936
        • Private hospitals: €14,872,779
      • Overall mean LOS [days (range)]:
        • SSI: 32 (13–62)
        • No SSI: 14 (3–42)
      • Mortality during 1 year study period [% (range)]:
        • SSI: 8.3% (0.4–16.0)
        • No SSI: 2.0% (0.0–13.1) (P < 0.001)
      LOS, length of stay; NR, not reported; SD, standard deviation; SSI, surgical site infection.

      Germany

      Two full SSI cost publications reporting the results of a matched case–control study were identified for Germany [
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ]. It should be noted that the two publications for Germany report equivalent data, but present the findings in difference currencies. The surgical specialty considered was cardiothoracic surgery (N = 2). The endpoints reported were the direct costs of infection (N = 2), cost drivers (N = 2), LOS (N = 2), and mortality (N = 2) (Table II).
      Table IIBurden of surgical site infection in Germany
      Study, publication type, study typeNo. of patientsEpidemiology results (incidence/prevalence)CostsProxy outcomes
      Cardiothoracic surgery (N = 2)
       Graf et al.
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      The 2010 publication reported costs in € and the 2011 publication reported costs in US$.


       Matched case–control study
      N = 51 (cases, n = 17; controls, n = 34)NR
      • Cost per patient (95% CI):
        • SSI: $49,449 (42,505, 65,835); €36,261 (31,028, 48,060)
        • No SSI: $18,218 (16,520, 24,561); €13,356 (12,060, 17,930) (P < 0.0001)
      • Cost per patient day:
        • SSI: $1,385; €1,011
        • No SSI: $1,599; €1,167 (ns)
      • LOS in hospital, days (95% CI):
        • SSI: 34.4 (30.1, 38.6)
        • No SSI: 16.5 (14.0, 17.5) (P = 0.0006)
      • Mortality during 27-month study period:
        • SSI: 17.6%
        • No SSI: 8.8% (P = 0.03)
      CI, confidence interval; LOS, length of stay; ns, not significant; NR, not reported; SSI, surgical site infection.
      a The 2010 publication reported costs in € and the 2011 publication reported costs in US$.

      The Netherlands

      The systematic review identified no eligible studies for the Netherlands.

      Italy

      One study reported the results of an SSI cost analysis in Italy [
      • Nobile M.
      • Navone P.
      • Orzella A.
      • Colciago R.
      • Calori G.M.
      Developing a model for analysis the extra costs associated with surgical site infections (SSIs): an orthopaedic and traumatological study run by the Gaetano Pini Orthopaedic Institute.
      ]. This study was detailed in an abstract and reported the direct costs associated with SSIs following orthopaedic and trauma surgery (Table III).
      Table IIIBurden of surgical site infection in Italy
      Study, publication type, study typeNo. of patientsEpidemiology results (incidence/prevalence)CostsProxy outcomes
      Orthopaedic and trauma surgery (N = 1)
       Nobile et al.
      • Nobile M.
      • Navone P.
      • Orzella A.
      • Colciago R.
      • Calori G.M.
      Developing a model for analysis the extra costs associated with surgical site infections (SSIs): an orthopaedic and traumatological study run by the Gaetano Pini Orthopaedic Institute.


       Cost analysis study
      N = 7NR
      • Direct cost associated with SSI:
        • Total extra cost of SSI: €32,000
        • Average cost per SSI: €9,560
        • Cost of hospital admissions: €3,411–€22,273
        • Cost borne by regional health service: €57,419
          • Average cost per case: €8,202
        • Cost borne by hospital: €8,513
          • Average cost per case: €1,216
      NR
      NR, not reported; SSI, surgical site infection.

      Spain

      Three full publications investigating the burden of SSIs were available for Spain, including a nested case–control study, a retrospective observational study, and an open-label comparative clinical study [
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ,
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ]. The surgical specialties considered in the studies were urology surgery (N = 1) and multiple surgical specialties (N = 2). Outcomes reported across the Spanish studies included study incidence of SSIs (N = 3), direct costs (N = 3), indirect costs (N = 1), LOS (N = 3), mortality (N = 2), and resource consumption (N = 1) (Table IV).
      Table IVBurden of surgical site infection in Spain
      Study, publication type, study typeNo. of patientsEpidemiology results (incidence/prevalence)CostsProxy outcomes
      Urology (N = 1)
       Gili-Ortiz et al.
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.


       Retrospective observational study
      N = 4377SSI incidence: 859 (19.4%)
      • Overruns attributable to SSI:
        • SSI: €33,533.4
        • No SSI: €18,657.7
      • Mean hospital LOS (days):
        • SSI: 37.4
        • No SSI: 19.6
      • Mortality rate among radical cystectomy patients during three-year study period:
        • SSI: 10.2%
        • No SSI: 4.2%
        • HR: 2.5 (95% CI: 1.9, 3.2) (P < 0.0001)
      Multiple surgical specialties (N = 2)
       Alfonso et al.
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.


       Nested case–control study
      N = 1962
      • Rates of SSI for all surgical patients:
        • Overall: 177 (9.02%)
          • In-hospital: 93 (4.74%)
          • Post-discharge: 84 (4.28%)
      • Total cost of prolonged LOS with SSI:
        • Total cost: $397,828
        • Per patient: $3,753
      • Direct healthcare cost of patients with SSI:
        • Total cost: $1,084,639
        • Per patient: $10,232
      • Total cost of SSI including indirect costs:
        • Total cost: $10,353,444
        • Per patient: $97,433
      • Mean LOS [days (SD)]:
        • SSI patients: 23.73 (19.89)
        • SSI post-discharge: 12.99 (4.09)
        • No SSI: 9.45 (2.51)
      • Mortality during 4.5-year study period:
        • Overall: NR (1.1%)
        • SSI-attributable: 21 (11.9%)
       Arroyo et al.
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.


       Open-label comparative clinical study
      N = 416 (gauze/tape group, n = 199; polyurethane group, n = 217)
      • Incidence of SSI:
        • Gauze/tape group: 13 (6.6%)
        • Polyurethane group: 3 (1.4%) (P = 0.006)
      • Total cost of postoperative management of superficial SSI:
        • Gauze/tape group: €59,400
        • Polyurethane group: €22,400
      • Hospital LOS, days (SD)
        • SSI: 9.5 (5.4)
        • No SSI: 7.4 (3.3) (P = 0.016)
      HR, hazard ratio; LOS, length of stay; NR, not reported; SD, standard deviation; SSI, surgical site infection.

      UK

      Sixteen of the eligible studies were based in the UK; 15 were full publications and one was an abstract [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ,
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Dhadwal K.
      • Al-Ruzzeh S.
      • Athanasiou T.
      • Choudhury M.
      • Tekkis P.
      • Vuddamalay P.
      • et al.
      Comparison of clinical and economic outcomes of two antibiotic prophylaxis regimens for sternal wound infection in high-risk patients following coronary artery bypass grafting surgery: a prospective randomised double-blind controlled trial.
      ,
      • Dholakia S.
      • Jeans J.P.
      • Khalid U.
      • Dholakia S.
      • D’Souza C.
      • Nemeth K.
      The association of noise and surgical-site infection in day-case hernia repairs.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Hahnel J.
      • Burdekin H.
      • Anand S.
      Re-admissions following hip fracture surgery.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ,
      • Leaper D.
      • Nazir J.
      • Roberts C.
      • Searle R.
      Economic and clinical contributions of an antimicrobial barrier dressing: a strategy for the reduction of surgical site infections.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ,
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]. Study designs included case–control studies (N = 2), surveillance studies (N = 2), randomized control trials (N = 2), prospective cohort studies (N = 3), retrospective cohort studies (N = 3), and cost analyses (N = 4). Surgical specialties considered in the studies were cardiothoracic surgery (N = 1), general surgery (N = 3), neurosurgery (N = 2), orthopaedic and trauma surgery (N = 6), and multiple surgical specialties (N = 4). Outcomes reported across the UK-based studies included study incidence of SSIs (N = 10), direct costs associated with SSI (N = 14), cost drivers (N = 5), HRQoL (N = 1), LOS (N = 12), mortality (N = 5), readmissions (N = 3), additional procedures (N = 2), and resource use (N = 1) (Table V).
      Table VBurden of surgical site infection in the UK
      Study, publication type, study typeNo. of patientsEpidemiology results (incidence/prevalence)CostsProxy outcomes
      Cardiothoracic surgery (N = 1)
       Dhadwal et al.
      • Dhadwal K.
      • Al-Ruzzeh S.
      • Athanasiou T.
      • Choudhury M.
      • Tekkis P.
      • Vuddamalay P.
      • et al.
      Comparison of clinical and economic outcomes of two antibiotic prophylaxis regimens for sternal wound infection in high-risk patients following coronary artery bypass grafting surgery: a prospective randomised double-blind controlled trial.


       Randomized control trial
      N = 186 (study group, n = 87; control group, n = 99)
      The study group received a single dose of gentamicin 2mg/kg, rifampicin 600mg and vancomycin 15mg/kg, with three further doses of 7.5mg/kg at 12h intervals. The control group received cefuroxime 1.5g at induction and three further doses of 750mg at 8h intervals.
      • Incidence of sternal wound infection at 90 days:
        • Study group: 8 (9.2%)
        • Control group: 25 (25.2%)
      • Mean cost of antibiotic use, cost (range):
        • Study group: $358 (31–12,714)
        • Control group: $454 (9–21,316)
      • Mean hospital cost, $1000 (range):
        • Study group: $14.8 (5.7–126.8)
        • Control group: $18.6 (5.7–97.3)
      • Mean postoperative hospital LOS [days (range)]:
        • Study group: 9.1 (4–73)
        • Control group: 12.0 (4–69)
      • Infection-related mortality during one-year study period:
        • Study group: 0
        • Control group: 2 (2.0%)
      General surgery (N = 3)
       Dholakia et al.
      • Dholakia S.
      • Jeans J.P.
      • Khalid U.
      • Dholakia S.
      • D’Souza C.
      • Nemeth K.
      The association of noise and surgical-site infection in day-case hernia repairs.


       Prospective cohort study
      N = 64Overall incidence of SSI: 5 (7.81%)Additional hospital cost of SSI per patient: £243NR
       Pinkney et al.
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.


       Randomized control trial
      N = 760 (wound edge protection, n = 382; standard intraoperative care, n = 378)
      • Incidence of SSI within 30 days of surgery:
        • Wound edge protection: 91 (24.7%)
        • Standard intraoperative care: 93 (25.4%) (P = 0.85)
      NR
      • Mean hospital LOS [days (IQR)]:
        • Wound edge protection: 9 (6–15)
          • SSI: 10 (7–20)
          • No SSI: 8 (6–14)
        • Standard intraoperative care: 9 (6–14) (P = 0.82):
          • SSI: 10 (7–22)
          • No SSI: 9 (6–13)
      • Number of deaths within 30 days of surgery:
        • Wound edge protection: 8/382
        • Standard intraoperative care: 12/378
       Tanner et al.
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.


       Surveillance study
      N = 105Incidence of SSI within 30 days of surgery: 29 (27.6%)
      • Additional costs of SSI patients:
        • Total: £305,173
          • Inpatient: £259,835 (85%)
          • Post discharge: £45,338 (15%)
        • Mean cost per patients: £10,523
          • Inpatient: £8,959.80
          • Post discharge: £1,563
      Mean LOS: on average 14 days longer for patients with an SSI, relative to those without

      Readmissions due to SSI: 3 patients
      Neurosurgery (N = 2)
       Atkinson et al.
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.


       Case–control study
      N = 17NR: 17 patients experienced

      SSI but total number of patients

      was NR
      • Direct costs (currency NR):
        • Costs were 2.5-fold higher in patients with SSI than in uninfected patients
      • Mean inpatient LOS for patients with SSI [days (SD)]:
        • Overall: 32 (15.4)
       O’Keeffe et al.
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.


       Cost analysis study
      N = 236 (245 craniotomy procedures)
      • Incidence of SSI:
        • Overall, 20 (8.4%)
      • Total additional cost associated with craniotomy infections:
        • Cost per infection: £9,283
        • Overall cost: £185,660
      • Mean LOS [days (SD)]:
        • SSI: 34 (27.9)
        • No SSI: 9.4 (6.1) (P < 0.001)
      Orthopaedic and trauma surgery (N = 6)
       Edwards et al.
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.


       Prospective cohort study
      N = 3563
      • Incidence of SSI:
        • Overall, 80 (2.3%)
      • Mean total cost:
        • SSI: £25,940
        • No SSI: £8,979
      • Mean LOS:
        • SSI: 76
        • No SSI: 22 (P = 0.001)
      • One-year mortality:
        • SSI: 26 (32.5%)
        • No SSI: 1116 (33.5%) (P = 0.954)
       Hahnel et al.
      • Hahnel J.
      • Burdekin H.
      • Anand S.
      Re-admissions following hip fracture surgery.


       Prospective cohort study
      N = 535NRNR
      • Number of emergency readmissions due to superficial SSI:
        • Overall, 2 (2.4%)
       Kallala et al.
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.


       Retrospective cohort study
      N = 168NR
      • Mean total costs of revision surgery [£ (SD)]:
        • SSI: £30,011 (4,514)
        • No SSI: £9,655 (599.7) (P < 0.0001)
      • Mean LOS [days (SD)]:
        • SSI: 21.49 (3.062%)
        • No SSI: 9.56 (0.71%) (P < 0.0001)
       Pollard et al.
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.


       Retrospective cohort study
      Infected cases, N = 61

      Controls, N = 122
      Incidence of deep wound infection over 6 years: 61 (2.5%)
      • Median cost of treatment per patient (IQR)
        • SSI: £24,410 (15,130–38,670)
        • No SSI: £7,210 (4290–10,780) (P < 0.001)
      • Median LOS [days (IQR)]
        • SSI: 80 (43–146)
        • No SSI: 28 (13–53)
      • Mortality at 6 months after initial fracture surgery:
        • SSI: 23 (37.7%)
        • No SSI: 32 (26.2%) (P = 0.111)
       Vanhegan et al.
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.


       Retrospective cohort study
      N = 286NR
      • Mean total costs [£ (SD)]:
        • Deep infection: 21,937 (10,965)
        • Aseptic loosening: 11,897 (4,629)
        • Per-prosthetic fracture: 18,185 (9,124)
        • Dislocation: 10,893 (5,476)
      • Mean LOS [days (SD)]:
        • Deep infection: 16.8 (22.3)
        • Aseptic loosening: 9.3 (8.6)
        • Per-prosthetic fracture: 17.1 (17.8)
        • Dislocation: 9.1 (4.2)
       Wijeratna et al.
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.


       Case-control study
      N = 525(hip hemi-arthroplasty, n = 415; total hip replacement, n = 110)Overall incidence of SSI: 17 (3.2%)
      • Mean total cost of inpatient stay
        • SSI: £15,576
        • No SSI: £6,922 (P < 0.00005)
      • Mean hospital LOS [days]
        • SSI: 39
        • No SSI: 16 (P < 0.001)
      Multiple or unspecified surgical specialties (N = 4)
       Coello et al.
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.


       Surveillance study
      NR: 67,410 surgical procedures were reported by the 140 participating hospitals
      • Incidence of SSI per 100 operations (95% CI):
        • Limb amputation: 14.3 (12.3, 16.4)
        • Small bowel surgery: 10.0 (7.7, 12.8)
        • Large bowel surgery: 10.0 (9.3, 10.8)
        • Vascular surgery: 7.7 (6.8, 8.6)
        • CABG: 4.2 (3.8, 4.6)
        • Open reduction of long bone fracture: 4.4 (3.7, 5.3)
        • Hip prosthesis: 3.1 (2.8, 3.3)
        • Knee prosthesis: 1.9 (1.7, 2.2)
          • Abdominal hysterectomy: 2.5 (2.1, 2.9)
      • Additional cost per SSI:
        Based on costs derived from Plowman et al. [44].
        • Limb amputation: £6,103
        • Small bowel surgery: £3,836
        • Large bowel surgery: £2,732
        • Vascular surgery: £3,545
        • CABG: £3,894
        • Open reduction of long bone fracture: £2,877
        • Hip prosthesis: £3,342
        • Knee prosthesis: £3,168
        • Abdominal hysterectomy: £959
      • Additional mean LOS for patients with SSI [days (95% CI)]:
        • Limb amputation: 21.0 (13.2, 31.1)
        • Small bowel surgery: 13.2 (6.5, 22.4)
        • Vascular surgery: 12.2 (9.8, 15.0)
        • Large bowel surgery: 9.4 (8.1, 10.8)
        • CABG: 13.4 (12.4, 14.6)
        • Long bone fracture open reduction: 9.9 (6.1, 14.6)
        • Hip prosthesis: 11.5 (10.3, 12.8)
        • Knee prosthesis: 10.9 (9.0, 13.0)
        • Abdominal hysterectomy: 3.3 (2.7, 4.0)
      • Mortality, range across surgical categories between October 1997 and June 2001:
        • SSI: 0.4–13.0
        • No SSI: 0.2–8.1
       Jenks et al.
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.


       Cost analysis study
      NR: 14,870 surgical episodes were followed
      • Incidence of all SSI:
        • SSI during admission: 162 (1.1%)
        • SSI on readmission: 120 (0.8%)
        • SSI post-discharge: 451 (3.2%)
        • Total SSI over 2 years: 733 (5.1%)
      • Median cost attributable to SSI (95% CI):
        • All surgical categories: £5,239 (4,622, 6,719)
      • 2-year costs attributable to SSI (range):
        • 2-year total cost of SSI: £2,491,424 [£19,469 (cholecystectomy) to £722,537 (cardiac)]
        • 2-year overall loss for SSI patients: £1,083,726
      • LOS in all surgical categories, days:
        • Total LOS attributable to SSI over 2 years: 4694
        • Median postoperative LOS, days (95% CI):
          • Non-SSI: 5 (5, 5)
          • SSI: 19 (17, 21)
      • Mortality during 2-year study period:
        • SSI: 21 deaths
          Total number of patients in the SSI and non-SSI groups was not reported.
        • Non-SSI: 490 deaths
          Total number of patients in the SSI and non-SSI groups was not reported.
       Leaper et al.
      • Leaper D.
      • Nazir J.
      • Roberts C.
      • Searle R.
      Economic and clinical contributions of an antimicrobial barrier dressing: a strategy for the reduction of surgical site infections.


       Cost analysis study
      NR: analysis was per 1000 operations
      • Estimated incidence of SSI per 1000 operations:
        • Postoperative film dressings: 100
        • Antimicrobial barrier dressing: 65
      • Cost per 1000 operations at an efficacy of 35%:
        • Postoperative film dressing:
          • Total cost: £320,600
          • Cost per procedure: £320.60
        • Antimicrobial barrier dressing:
          • Total cost: £239,710
          • Cost per procedure: £239.70
      • Infection-attributable bed-days per 1000 operations:
        • Postoperative film dressing: 1100
        • Antimicrobial barrier dressing: 715
       Wilson et al.
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.


       Cost analysis study
      N = 15,548Overall incidence of wound infections (SSI criteria): 382 (9.9%)
      • Mean cost according to ASEPSIS score:
        • Infected patient (ASEPSIS >10): £7,718
        • Uninfected patients (ASEPSIS <10): £3,700
      NR
      CABG, coronary artery bypass graft; CI, confidence interval; IQR, interquartile range; LOS, length of stay; NR, not reported; OR, odds ratio; PFF, proximal femoral fracture; SD, standard deviation; SSI, surgical site infection.
      a The study group received a single dose of gentamicin 2mg/kg, rifampicin 600mg and vancomycin 15mg/kg, with three further doses of 7.5mg/kg at 12h intervals. The control group received cefuroxime 1.5g at induction and three further doses of 750mg at 8h intervals.
      b Based on costs derived from Plowman et al.
      • Plowman R.
      • Graves N.
      • Griffin M.A.
      • Roberts J.A.
      • Swan A.V.
      • Cookson B.
      • Taylor L.
      The rate and cost of hospital-acquired infections occurring in patients admitted to selected specialties of a district general hospital in England and the national burden imposed.
      .
      c Total number of patients in the SSI and non-SSI groups was not reported.

      Costs

      France

      The four studies available for France reported substantial additional costs due to SSIs. Penel et al. reported that following head and neck cancer surgery, patients who developed an SSI constitute a total per-patient medical cost €17,434 higher than those patients who did not develop an SSI. The total cost estimation considered the additional laboratory testing, prolonged hospitalization, medication costs and medical staff costs (Table I) [
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ].

      Germany

      The matched case–control study in Germany demonstrated that the total medical cost per patient was significantly elevated in patients who contracted an SSI [$49,449 vs $18,218 (€36,261 vs €13,356) for SSI patients and uninfected patients, respectively]. The results indicated that for patients who developed an SSI, intensive care unit (ICU) and ward-care costs accounted for the largest costs (27.7% and 24.7%, respectively), whereas costs associated with laboratory tests and other hospital costs were not higher for infected patients compared with controls (Table II) [
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ].

      Italy

      Nobile et al. reported that in orthopaedic and trauma surgery patients, the development of an SSI was associated with additional total medical costs of €32,000, relative to uninfected patients, corresponding to an average cost per SSI of €9,560 [
      • Nobile M.
      • Navone P.
      • Orzella A.
      • Colciago R.
      • Calori G.M.
      Developing a model for analysis the extra costs associated with surgical site infections (SSIs): an orthopaedic and traumatological study run by the Gaetano Pini Orthopaedic Institute.
      ]. It was noted that the abstract did not specify which resources and costs were considered in the estimation of the total cost of SSIs (Table III).

      Spain

      Surgical site infections were associated with elevated costs in the three studies available for Spain [
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ,
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ]. Alfonso et al. reported that across multiple surgical specialties, the direct total healthcare cost of developing an SSI was $1,084,639, which was mainly attributable to prolonged hospitalization (37%) and other hospital costs (43%). Primary healthcare costs and antibiotic costs accounted for 14% and 6%, respectively. When indirect costs such as SSI-related morbidity/mortality and societal costs were also considered, healthcare costs only accounted for about 10.5% of the total financial burden. Interestingly, Alfonso et al. also demonstrated that SSI-related costs were positively correlated with increasing age, with SSI patients >80 years representing the largest financial burden (Table IV) [
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ].

      UK

      Multiple studies reported that various surgical specialties were associated with elevated costs following the development of an SSI [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ,
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Dhadwal K.
      • Al-Ruzzeh S.
      • Athanasiou T.
      • Choudhury M.
      • Tekkis P.
      • Vuddamalay P.
      • et al.
      Comparison of clinical and economic outcomes of two antibiotic prophylaxis regimens for sternal wound infection in high-risk patients following coronary artery bypass grafting surgery: a prospective randomised double-blind controlled trial.
      ,
      • Dholakia S.
      • Jeans J.P.
      • Khalid U.
      • Dholakia S.
      • D’Souza C.
      • Nemeth K.
      The association of noise and surgical-site infection in day-case hernia repairs.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Hahnel J.
      • Burdekin H.
      • Anand S.
      Re-admissions following hip fracture surgery.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ,
      • Leaper D.
      • Nazir J.
      • Roberts C.
      • Searle R.
      Economic and clinical contributions of an antimicrobial barrier dressing: a strategy for the reduction of surgical site infections.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ,
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]. For example, Tanner et al. reported that general surgery patients who contracted an SSI constituted an additional healthcare financial burden of £10,523 per patient [
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ]. Cost drivers identified in this study included prolonged LOS, treatment costs and readmission costs. Several studies demonstrated that the primary cost driver was prolonged postoperative hospitalization of infected patients, relative to uninfected patients [
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ]. Additional expenditure was also attributed to operative costs, medical staff costs, and investigation and treatment costs [
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ]. For example, Jenks et al. reported that operating theatre and medical staff costs accounted for 11% and 18% of the total additional costs associated with infection, respectively [
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ]. Notably, the cost burden was greater for patients who developed deep SSIs compared with superficial infections (Table V) [
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ].

      Proxy outcomes

      Proxy outcomes for which a cost could be applied included LOS, mortality, readmissions, and the number of additional procedures required. Length of stay in hospital was higher among patients who developed an SSI relative to uninfected patients; this was true for all studies in the six European countries and across all surgical specialties. The highest number of days required in hospital following the development of an SSI was recorded after orthopaedic and trauma surgery in the UK (an additional 54 days with an SSI) [
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ]. Conversely, prolonged hospitalization was lowest for one study in Spain, which reported an additional LOS of 2.1 days among patients who develop SSIs after multiple or unspecified surgical specialties [
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ]. However, variability existed between LOS reported in studies in the same country as well for the same surgical specialty (Figure 2) [
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ].
      Figure 2
      Figure 2Additional lenth of hospital stay (LOS) associated with surgical site infection (SSI) versus no SSI. Additional LOS in hospital (days) reported among patients who developed an SSI, compared with uninfected patients. Numbers along the x-axis denote the study: 1, Cossin et al.
      [
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ]
      ; 2, Penel et al.
      [
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ]
      ; 3, Lamarsalle et al.
      [
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ]
      ; 4, Graf et al.
      [
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ]
      ; 5, Gili-Ortiz et al.
      [
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ]
      ; 6, Alfonso et al.
      [
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ]
      ; 7, Arroyo et al.
      [
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ]
      ; 8, O’Keefe et al.
      [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ]
      ; 9, Edwards et al.
      [
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ]
      ; 10, Kallala et al.
      [
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ]
      ; 11, Wijeratna et al.
      [
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ]
      ; 12, Tanner et al.
      [
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ]
      ; 13, Atkinson et al.
      [
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]
      . LOS, length of stay; SSI, surgical site infection.

      France

      All three studies reporting LOS demonstrated that hospitalization was prolonged in patients who developed an SSI compared with uninfected patients [
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ,
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ]. Indeed, Penel et al. reported that the mean duration of hospitalization for patients who develop an SSI following head and neck cancer surgery was 15.3 days longer than for uninfected patients [
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ]. Cossin et al. reported that the mean duration of post-surgery hospitalization among patients who contracted an SSI after cardiothoracic surgery was 2.3 times higher than for those who did not. In addition, Lamarsalle et al. reported that mortality during a one-year study period was significantly higher in SSI patients relative to controls (8.3% vs 2.0%, respectively) (Table I) [
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ].

      Germany

      The development of an SSI following cardiothoracic surgery necessitated prolonged hospitalization. Graf et al. reported that mean LOS in SSI patients was 17.9 days longer than for those who did not contract an infection. In addition, the percentage mortality rate was double in patients who developed an SSI compared with that of uninfected patients (Table II) [
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ].

      Spain

      All three studies consistently reported that SSIs are responsible for prolonged hospitalization relative to uninfected patients. Accordingly, Gili-Ortiz et al. reported that mean LOS was 17.8 days longer among patients who contracted an SSI following radical cystectomy surgery, compared with uninfected patients [
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ]. This study also highlighted that the percentage mortality rate among SSI patients after surgery was about 2.4 times higher than among those who did not develop an SSI (Table IV).

      UK

      Multiple studies demonstrated that the length of hospitalization was greater in patients who contracted an SSI following surgery, compared with uninfected patients [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ,
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]. Interestingly, Coello et al. highlighted that the additional LOS after contraction of an SSI varied between surgical specialties, ranging from 3.3 days (abdominal hysterectomy) to 21.0 days (limp amputation) [
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ]. The length of hospitalization following the development of an SSI also varied between surgical specialties in other UK studies, ranging from an additional 11.93 days following knee prosthesis surgery, to 54 additional days after hip fracture surgery [
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ]. It was also noted that hospitalization was longer for patients who developed a deep SSI compared with a superficial infection [
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ]. SSIs were reported to result in increased hospital readmissions and reoperations compared with uninfected patients [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Hahnel J.
      • Burdekin H.
      • Anand S.
      Re-admissions following hip fracture surgery.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ]. Notably, patients who underwent orthopaedic and trauma surgery and developed a deep SSI (N = 8) had a total of 14 reoperations in addition to their index procedure [
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ]. Furthermore, Tanner et al. reported that three out of 29 patients who contracted an SSI after general surgery were readmitted following hospital discharge. Increased mortality rates among SSI patients were also reported relative to those who did not contract an SSI (Table V) [
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ].

      Quality of life

      Eligible studies reporting SSI QoL data were only available for one study in the UK. The study was a full publication detailing the results of a randomized control study conducted in 2013 [
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ]. EQ-5D scores demonstrated that SSIs negatively impact on patient HRQoL, demonstrated by a statistically significant reduction in HRQoL scores (11%) at 30 days in patients who underwent laparotomy surgery, relative to patients who did not develop an SSI [
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ]. It is noteworthy that the results of this study were also included in a recent systematic review by Gheorghe et al., who reported that the SSI utility decrement in patients who developed an SSI after laparotomy surgery was 0.05 at 7 days and 0.12 at 30 days (Table V) [
      • Gheorghe A.
      • Moran G.
      • Duffy H.
      • Roberts T.
      • Pinkney T.
      • Calvert M.
      Health utility values associated with surgical site infection: a systematic review.
      ].

      Discussion

      This systematic review confirms that a significant number of SSIs occur following various surgical specialties in European countries. The incidence of SSI was as high as 36% in one of the studies reviewed, demonstrating that infections constitute a persistent complication of surgery [
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ]. Analysis of the 26 eligible studies confirmed that the financial burden of surgery is consistently higher in patients who develop an SSI, relative to uninfected patients [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ,
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Defez C.
      • Fabbro-Peray P.
      • Cazaban M.
      • Boudemaghe T.
      • Sotto A.
      • Daures J.P.
      Additional direct medical costs of nosocomial infections: an estimation from a cohort of patients in a French university hospital.
      ,
      • Dhadwal K.
      • Al-Ruzzeh S.
      • Athanasiou T.
      • Choudhury M.
      • Tekkis P.
      • Vuddamalay P.
      • et al.
      Comparison of clinical and economic outcomes of two antibiotic prophylaxis regimens for sternal wound infection in high-risk patients following coronary artery bypass grafting surgery: a prospective randomised double-blind controlled trial.
      ,
      • Dholakia S.
      • Jeans J.P.
      • Khalid U.
      • Dholakia S.
      • D’Souza C.
      • Nemeth K.
      The association of noise and surgical-site infection in day-case hernia repairs.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ,
      • Hahnel J.
      • Burdekin H.
      • Anand S.
      Re-admissions following hip fracture surgery.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ,
      • Leaper D.
      • Nazir J.
      • Roberts C.
      • Searle R.
      Economic and clinical contributions of an antimicrobial barrier dressing: a strategy for the reduction of surgical site infections.
      ,
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ,
      • Nobile M.
      • Navone P.
      • Orzella A.
      • Colciago R.
      • Calori G.M.
      Developing a model for analysis the extra costs associated with surgical site infections (SSIs): an orthopaedic and traumatological study run by the Gaetano Pini Orthopaedic Institute.
      ,
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]. Indeed, Edwards et al. reported that in England, the mean total cost of orthopaedic and trauma surgery in those who developed an SSI was about 2.9 times higher than the costs associated with patients who did not [
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ].
      Several studies consistently demonstrated that hospitalization was prolonged for patients who developed an SSI following surgery compared with uninfected patients [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ,
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ,
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ,
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Kallala R.F.
      • Ibrahim M.S.
      • Sarmah S.
      • Haddad F.S.
      • Vanhegan I.S.
      Financial analysis of revision knee surgery based on NHS tariffs and hospital costs. Does it pay to provide a revision service?.
      ,
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ,
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Wijeratna M.D.
      • McRoberts J.
      • Porteous M.J.
      Cost of infection after surgery for intracapsular fracture of the femoral neck.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ]. This is exemplified in a French study by Cossin et al. who reported that following cardiothoracic surgery, the mean duration of post-surgery hospitalization for patients who developed an SSI was 2.3 times higher than that of uninfected patients [
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ]. Prolonged LOS on general wards and in the ICU as a result of contracting an SSI was reported to constitute a major cost burden in multiple studies [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ,
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Edwards C.
      • Counsell A.
      • Boulton C.
      • Moran C.G.
      Early infection after hip fracture surgery.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ,
      • Pollard T.C.
      • Newman J.E.
      • Barlow N.J.
      • Price J.D.
      • Willett K.M.
      Deep wound infection after proximal femoral fracture: consequences and costs.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Vanhegan I.S.
      • Malik A.K.
      • Jayakumar P.
      • Ul Islam S.
      • Haddad F.S.
      A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ]. The number of days of hospitalization varied between countries and surgical specialties; however, comparable LOS following the development of an SSI after cardiothoracic surgery was reported between studies, with an average of 15.5 days [
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ]. It should also be noted that the cost per day of hospitalization differed between studies and countries; for example, whereas Penel et al. estimated the cost per day of hospitalization at €1,140 per day, Arroyo et al. estimated it at €350 per day [
      • Arroyo A.A.
      • Casanova P.L.
      • Soriano J.V.
      • Torra i Bou J.E.
      Open-label clinical trial comparing the clinical and economic effectiveness of using a polyurethane film surgical dressing with gauze surgical dressings in the care of post-operative surgical wounds.
      ,
      • Penel N.
      • Lefebvre J.L.
      • Cazin J.L.
      • Clisant S.
      • Neu J.C.
      • Dervaux B.
      • Yazdanpanah Y.
      Additional direct medical costs associated with nosocomial infections after head and neck cancer surgery: a hospital-perspective analysis.
      ]. This variation is likely attributable to the inclusion of different parameters in the defined daily hospitalization cost (e.g. overhead, laboratory, diagnosis, healthcare professional costs).
      In addition to prolonged hospitalization, expenditure was also attributed to investigation and treatment costs, operative costs, and medical staff costs [
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Coello R.
      • Charlett A.
      • Wilson J.
      • Ward V.
      • Pearson A.
      • Borriello P.
      Adverse impact of surgical site infections in English hospitals.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ,
      • Tanner J.
      • Khan D.
      • Aplin C.
      • Ball J.
      • Thomas M.
      • Bankart J.
      Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.
      ,
      • Wilson A.P.
      • Hodgson B.
      • Liu M.
      • Plummer D.
      • Taylor I.
      • Roberts J.
      • et al.
      Reduction in wound infection rates by wound surveillance with postdischarge follow-up and feedback.
      ]. Alfonso et al. reported that whereas LOS accounted for 37% of total costs associated with SSIs after multiple surgical specialties, primary healthcare costs (14%), antibiotic costs (6%), and other hospital costs (43%) were also incurred. Furthermore, several studies reported that SSIs were associated with an increased requirement for reoperation, readmission, and increased mortality rates [
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Gili-Ortiz E.
      • Gonzalez-Guerrero R.
      • Bejar-Prado L.
      • Lopez-Mendez J.
      • Ramirez-Ramirez G.
      Surgical site infections in patients who undergo radical cystectomy: excess mortality, stay prolongation and hospital cost overruns.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Haverich A.
      • Chaberny I.F.
      Economic aspects of deep sternal wound infections.
      ,
      • Graf K.
      • Ott E.
      • Vonberg R.P.
      • Kuehn C.
      • Schilling T.
      • Haverich A.
      • Chaberny I.F.
      Surgical site infections – economic consequences for the health care system.
      ,
      • Lamarsalle L.
      • Hunt B.
      • Schauf M.
      • Szwarcensztein K.
      • Valentine W.J.
      Evaluating the clinical and economic burden of healthcare-associated infections during hospitalization for surgery in France.
      ,
      • Atkinson R.A.
      • Jones A.
      • Ousey K.
      Management and cost of surgical site infection in patients undergoing surgery for spinal metastasis.
      ]. For example, nine out of 20 patients who developed an infection after neurosurgery in the UK required reoperation, amounting to an overall cost of more than £7,000 [
      • O'Keeffe A.B.
      • Lawrence T.
      • Bojanic S.
      Oxford craniotomy infections database: a cost analysis of craniotomy infection.
      ]. The need for costly reoperations as a result of infection has subsequently fuelled consideration of cost-effective non-surgical treatments in high-risk patients [
      • Urban J.A.
      Cost analysis of surgical site infections.
      ].
      There was considerable heterogeneity between the identified SSI studies, with a number of data gaps in the economic and HRQoL evidence available, and so a quantitative analysis of the studies (meta-analysis) was not deemed appropriate. This highlights the ongoing need for well-designed studies that use a common approach to patient selection, definition of endpoints, and follow-up. First, no economic or HRQoL evidence was found for the Netherlands, and, with the exception of the UK, only a limited number of studies were identified for the other countries. It is also noteworthy that the generalizability of economic evidence between countries is unknown due to the varying healthcare systems, finance structures, and currencies. Additionally, the evidence available according to surgical specialty was not evenly distributed across the six European countries. Very few studies reported the additional costs associated with SSI following orthopaedic and trauma surgery, otolaryngology or urology surgery. Furthermore, studies grouped into the same surgical specialty may not be directly comparable due to differences in surgical procedures; this is especially true for studies assigned to ‘multiple or unspecified surgery’. The presentation of cost and proxy results also varied between studies, e.g. LOS was not consistently reported, making comparisons difficult without manipulation of the data. Furthermore, the definition used to classify SSI differed, although the criteria defined by the CDC were the most widely employed [
      • Horan T.C.
      • Gaynes R.P.
      • Martone W.J.
      • Jarvis W.R.
      • Emori T.G.
      CDC definitions of nosocomial surgical site infections, 1992: a modification of CDC definitions of surgical wound infections.
      ]. These variables make accurate cost comparisons between different studies, surgical specialties, and countries very challenging, and are similar to those reported elsewhere in the literature [
      • Broex E.C.
      • van Asselt A.D.
      • Bruggeman C.A.
      • van Tiel F.H.
      Surgical site infections: how high are the costs?.
      ,
      • Alfonso J.L.
      • Pereperez S.B.
      • Canoves J.M.
      • Martinez M.M.
      • Martinez I.M.
      • Martin-Moreno J.M.
      Are we really seeing the total costs of surgical site infections? A Spanish study.
      ,
      • Cossin S.
      • Malavaud S.
      • Jarno P.
      • Giard M.
      • L’Hériteau F.
      • Simon L.
      • et al.
      Surgical site infection after valvular or coronary artery bypass surgery: 2008–2011 French SSI national ISO-RAISIN surveillance.
      ,
      • Birgand G.
      • Lepelletier D.
      • Baron G.
      • Barrett S.
      • Breier A.C.
      • Buke C.
      • et al.
      Agreement among healthcare professionals in ten European countries in diagnosing case-vignettes of surgical-site infections.
      ,
      • Yasunaga H.
      • Ide H.
      • Imamura T.
      • Ohe K.
      Accuracy of economic studies on surgical site infection.
      ].
      It is noteworthy that the majority of studies reviewed here do not consider the wider impact of SSI to society. For example, patients who require absence from work constitute an economic cost in terms of lost income and reduced work productivity. A further consideration is that not all infected patients will be diagnosed before their discharge from hospital; these patients may not have the same access to treatment, and infection may consequently cause more distress than for patients who are diagnosed in hospital [
      • Sanger P.C.
      • Hartzler A.
      • Han S.M.
      • Armstrong C.A.
      • Stewart M.R.
      • Lordon R.J.
      • et al.
      Patient perspectives on post-discharge surgical site infections: towards a patient-centered mobile health solution.
      ]. Infections not detected in hospital may also result in an underreporting of SSIs, as well as the costs associated with community healthcare visits [
      • Weber W.P.
      • Zwahlen M.
      • Reck S.
      • Feder-Mengus C.
      • Misteli H.
      • Rosenthal R.
      • et al.
      Economic burden of surgical site infections at a European university hospital.
      ,
      • Limón E.
      • Shaw E.
      • Badia J.
      • Piriz M.
      • Escofet R.
      • Gudiol F.
      • et al.
      Post-discharge surgical site infections after uncomplicated elective colorectal surgery: impact and risk factors. The experience of the VINCat Program.
      ]. It is therefore highly likely that the results of this review underestimate the true economic burden of SSI in the six European countries.
      In addition to the economic burden, the development of an SSI and the subsequent prolonged hospitalization will likely have a negative impact on patient physical and mental health. Indeed, Pinkney et al. reported that SSIs negatively affect patients’ health utilities, relative to patients who do not develop an SSI [
      • Pinkney T.
      • Calvert M.
      • Bartlett D.
      • Gheorghe A.
      • Redman V.
      • Dowswell G.
      • et al.
      The impact of wound-edge protection devices on surgical site infection after laparotomy (ROSSINI trial): a multicentre randomised controlled trial.
      ]. However, this was the only eligible study identified in the current review, highlighting the lack of QoL studies in the six European countries of interest. A recent systematic review by Gheorghe et al. reported that reliable health utility estimates and comparisons are currently hindered by too few studies, small sample sizes, and implicit records outlining SSI status at the time of assessment [
      • Gheorghe A.
      • Moran G.
      • Duffy H.
      • Roberts T.
      • Pinkney T.
      • Calvert M.
      Health utility values associated with surgical site infection: a systematic review.
      ]. Notably, the review by Gheorghe et al. also emphasized that there are fewer health utility studies in Europe, with the majority of SSI model-based economic evaluations being from an American perspective. It is therefore highly recommended that more studies be undertaken in Europe to determine whether, and to what extent, SSIs are associated with QoL decrements.
      Increased costs due to SSI may negate the current efforts to provide efficient and sustainable healthcare; for example, increased hospitalization as a result of SSI may delay subsequent patients’ surgery. It has also been demonstrated that there is a growing demand for surgical procedures, which will further exacerbate the problem of SSI and highlights the need for prompt action []. Whereas it has been suggested that one current system of reimbursement in an English hospital is a financial disincentive to reduce SSIs, contradictory findings suggest that if SSI rates are reduced, hospitals should expect increases in costs (e.g. due to costly intervention programmes) as well as revenue (e.g. as a result of increased hospital admissions) [
      • Jenks P.J.
      • Laurent M.
      • McQuarry S.
      • Watkins R.
      Clinical and economic burden of surgical site infection (SSI) and predicted financial consequences of elimination of SSI from an English hospital.
      ,
      • Shepard J.
      • Ward W.
      • Milstone A.
      • Carlson T.
      • Frederick J.
      • Hadhazy E.
      • Perl T.
      Financial impact of surgical site infections on hospitals: the hospital management perspective.
      ]. The ECDC provides a recognized framework to standardize reporting of SSIs; however, it may not be used by all European publications and surveillance schemes, leading to heterogeneous reporting of SSI rates and costs, and subsequently weakening any comparisons between European countries [
      • Birgand G.
      • Lepelletier D.
      • Baron G.
      • Barrett S.
      • Breier A.C.
      • Buke C.
      • et al.
      Agreement among healthcare professionals in ten European countries in diagnosing case-vignettes of surgical-site infections.
      ]. There is a need for renewed efforts to standardize procedures and reporting of SSI across European countries, with particular focus given to preventive strategies to avoid the associated costs of infection.
      In conclusion, this review has demonstrated that SSIs represent a substantial financial burden in European countries. Further evidence using robust and common methodologies is required to make accurate cost estimations, and there is a clear need for studies that investigate the impact of contracting an SSI on patient QoL. Generalizability of economic evidence between studies is difficult due to the varying finance structures, healthcare systems, and currencies. Nonetheless, the majority of infection-associated costs arise from prolonged hospitalization, with additional expenditure attributable to medical staff and treatment. Furthermore, SSIs negatively impact on patient outcomes, increasing patient morbidity, mortality, and HRQoL. As the demand for surgical procedures rises, the incidence and associated costs of SSIs will likely escalate. Thus, this review highlights the need for renewed efforts from European countries to improve quality of care and consequently reduce the financial burden of SSIs.

      Acknowledgements

      The authors are grateful to C. Hopley and I. Demeyer, both of whom are employees of Becton Dickinson and provided insight that greatly assisted the preparation of the manuscript. The authors also thank P. White, who is an employee of DRG Abacus and contributed to the writing and editing of the manuscript.

      Conflict of interest statement

      J. Badia, A. Casey and N. Petrosillo were paid consultants to Becton Dickinson & Co. in connection with the development of the manuscript. P. Hudson and S. Mitchell are both employees of DRG Abacus, the medical communication company that conducted the systematic review and provided writing services. Work by DRG Abacus was funded by Becton Dickinson & Co.; C. Crosby is an employee of Becton Dickinson & Co.

      Funding source

      This work was funded by Becton Dickinson & Co.

      Appendix A. Supplementary data

      The following is the supplementary data related to this article:

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