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Keywords:

  • Contact isolation;
  • cost-benefit;
  • decolonization;
  • economic analysis;
  • MRSA;
  • screening

Abstract

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) incur significant costs. We aimed to examine the cost and cost–benefit of infection control interventions against MRSA and to examine factors affecting economic estimates. We performed a systematic review of studies assessing infection control interventions aimed at preventing spread of MRSA in hospitals and reporting intervention costs, savings, cost–benefit or cost-effectiveness. We searched PubMed and references of included studies with no language restrictions up to January 2012. We used the Quality of Health Economic Studies tool to assess study quality. We report cost and savings per month in 2011 US$. We calculated the median save/cost ratio and the save–cost difference with interquartile range (IQR) range. We examined the effects of MRSA endemicity, intervention duration and hospital size on results. Thirty-six studies published between 1987 and 2011 fulfilled inclusion criteria. Fifteen of the 18 studies reporting both costs and savings reported a save/cost ratio >1. The median save/cost ratio across all 18 studies was 7.16 (IQR 1.37–16). The median cost across all studies reporting intervention costs (n = 31) was 8648 (IQR 2025–19 170) US$ per month; median savings were 38 751 (IQR 14 206–75 842) US$ per month (23 studies). Higher save/cost ratios were observed in the intermediate to high endemicity setting compared with the low endemicity setting, in hospitals with <500-beds and with interventions of >6 months. Infection control intervention to reduce spread of MRSA in acute-care hospitals showed a favourable cost/benefit ratio. This was true also for high MRSA endemicity settings. Unresolved economic issues include rapid screening using molecular techniques and universal versus targeted screening.


Background

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) incur significant morbidity, mortality and costs [1-3]. The adjusted odds ratio for death following MRSA bacteraemia compared with methicillin-sensitive S. aureus (MSSA) bacteraemia was estimated at 1.88 (95% CI 1.33–2.69) [4]. In the Netherlands, the additional length of stay for a patient with MRSA bacteraemia compared with MSSA bacteraemia was estimated at 10 days, with additional costs of €6372 (2011 US$9688) per patient [5]. An attributable in-hospital cost of €380 million was estimated for MRSA infections in EU healthcare systems [6]. In a review of the economic consequences of MRSA, the average cost of an MRSA-infected patient in Canada was estimated at US$12 216, with hospitalization being the major cost driver (81%), followed by barrier precautions (13%), antimicrobial therapy and laboratory investigations [7].

Intensive efforts to decrease MRSA infections in some European countries have resulted in significant reductions in MRSA incidence [8]. According to the European Antimicrobial Resistance Surveillance System annual report in 2012, 22.8%% of all S. aureus bacteraemias reported in 2012 were methicillin-resistant, a significant decrease from 41.9% reported in 2006. In the UK, there was a 56% reduction in the number of reported MRSA bacteraemias between 2004 and 2008 [9].

Such intensive efforts are costly and the cost-effectiveness of these efforts at the hospital or national level has not been defined [10]. The main infection control interventions used against MRSA include screening, contact isolation, cohorting and decolonization in addition to standard precautions. Contact isolation requires personal protective equipment; screening programmes incur laboratory costs (especially if rapid molecular techniques are used), consumables costs, clinical staff costs and decolonization costs; patient cohorting requires dedicated nursing staff. Costs more complicated to account for include those related to initial building and construction, restriction of number of beds in an intensive care unit, closure of a unit, closure of an operating room or cancellation of an operation.

We performed a systematic review of primary studies reporting on the cost-effectiveness, cost–benefit or costs alone of infection control interventions aimed at preventing spread of MRSA. We aimed to provide an overview of empirical studies, to obtain a cost–benefit estimate and to examine factors affecting economic estimates.

Methods

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

We included studies assessing infection control interventions aimed at preventing spread of MRSA in hospitals. Interventions included implementation of surveillance for MRSA, screening with or without decolonization, contact isolation, droplet isolation, environmental control and antibiotic stewardship. Studies were included if they reported at least one of the following economic analyses: costs of the intervention (intervention cost), costs related to benefit/gain following the intervention (savings), cost–benefit or cost-effectiveness. Any unit of effectiveness could be assessed in cost-effectiveness analyses, including life-years, quality-adjusted life years or infections prevented. We included studies in which cost assessment was based on primary study data; we excluded decision analytic models where the input to the model was based solely on literature review. We excluded studies evaluating costs of laboratory tests or equipment only and studies assessing only benefit by considering a single class of antibiotics.

We searched PubMed until January 2012 using a structured search clause (Appendix 1) and the reference lists of all included articles. We imposed no date or language restrictions. Conference proceedings were not sought because we expected that the level of information provided in an abstract would be insufficient. Two reviewers independently applied inclusion criteria and extracted the data from included studies. Differences in the data extracted were resolved by discussion with a third review author. Justification for excluding studies from the review was documented.

We primarily aimed to extract the costs of the intervention and the economic gain following the intervention. When economic consequences of the intervention were reported at several time points, we extracted all time points and used the longest follow up in the primary analysis. When sensitivity analyses were performed, we extracted base-case figures. We extracted not only the total sum of costs and savings, but also the individual components including personnel (separating nurse, physician and laboratory technician time), materials, antimicrobials, laboratory costs, building and refurbishment. We attempted to extract data on indirect costs, including intangible and productivity losses qualitatively. In addition, we extracted data on the components of the infection control intervention, baseline MRSA endemicity and the effects of the intervention on clinical infections and colonization with MRSA. We based MRSA endemicity rates on the percentage of methicillin-resistant isolates out of all S. aureus clinical isolates (usually bacteraemia): <1% low, 1–10% moderate and >10% high [11].

We used the Quality of Health Economic Studies (QHES) tool, adapted for our review, to assess the studies' quality (Appendix 2). The original QHES instrument contains 16 criteria, each with a weighted point value and the maximal score is 100 [12]. As we assessed primary studies rather than economic models, some of the QHES criteria were not relevant. Hence, in the adapted tool, the maximal score was 86 for studies providing cost–benefit or cost-effectiveness analyses and 50 for studies reporting on costs alone. We examined the effect of the revised QHES score on results through subgroup analysis.

We expressed costs per month considering the intervention duration for intervention costs and the duration of follow-up for the save costs. We calculated the save/cost ratio (values >1 indicating savings larger than costs) and the save–cost difference (positive values indicating net saving), adjusted to 2011 US$. All costs reported are in 2011 US$ per month. Since cost values were not normally distributed, highly heterogeneous and reported without a dispersion measure, no formal meta-analysis was performed. We calculated summary median cost, save, ratio and difference values with range (minimum–maximum) or interquartile range (IQR) (25–75% centile). When a range of cost values was reported, we used the median of the range for the summary estimate. We hypothesized a priori that heterogeneity will stem from the types of interventions, hospital size, population screened and prevalence of MRSA carriage.

Results

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

Potentially eligible articles were selected for full-text inspection, of which 36 studies fulfilled the inclusion criteria (Fig. 1). The studies were published between 1987 and 2011 and all but one were conducted in acute care hospitals (Table 1). Eighteen included both the intervention cost and save estimates [13-30] and 18 studies reported only on the cost [5, 31-43] or save [44-47] estimate. All studies examined the costs associated with implementation of a new or existing infection control intervention, whereas one recent study assessed the costs and harms associated with discontinuation of contact precautions for MRSA carriers [40]. The studies were most commonly conducted in hospitals with high MRSA endemicity (17 studies) and two were performed during an outbreak of MRSA. The intervention durations ranged between 2 months and 10 years.

Table 1. Description and quality assessment of included studies
Study IDCountryYear startIntervention targetDuration of interventionMRSA prevalenceType of cost-effectiveness analysisQHES score
  1. ICU, intensive care unit; MRSA, methicillin-resistant Staphylococcus aureus; NS, not stated; QHES, Quality of Health Economic Studies tool.

  2. The search and destroy policy most commonly included screening of patients with risk factors at hospital admission and follow-up screening during the hospital stay, isolation and decontamination of colonized patients or isolation and antimicrobial treatment of infected patients with MRSA.

  3. a

    MRSA endemicity not reported, but the study was conducted in the ‘septic’ ward treating 35% of all patients with MRSA.

Wernitz [13]Germany1999Hospital-wide, 700 beds19 monthsLowCost–benefit58
Simoens [14]Belgium2007Hospital-wide, 1900 beds3 monthsIntermediateCost–benefit45
van Rijen [15]Netherlands2001Hospital-wide, 1370 beds6 yearsLowCost–benefit36
Vriens [16]Netherlands1991Hospital-wide, 1042 beds10 yearsLowCost–benefit, cost real, benefit hypothetical7
Rao [17]Pittsburg, USA1987Hospital-wide, 464 beds2 monthsHighCost real benefit assumed from period before15
Nixon [18]UK2003Three orthopaedic wards, 3253 admissions5 monthsHighCost–benefit, cost real, benefit hypothetical18
West [19]South Carolina, USA2002Two hospitals. Total 580 beds4 monthsHighCost-effectiveness—cost per infection prevented. cost real, benefit taken from literature38
Clancy [20]Denver, USA2003Two ICUs, total 44 beds15 monthsHighCost–benefit, cost real, benefit hypothetical53
Knausz [21]Hungary2007Hospital-wide, 1400 beds24 months HighCost–benefit, cost real, benefit hypothetical29
Karchmer [22]Virginia, USANSNeonatal ICU, 33 beds10.5 monthsOutbreakCost–benefit, cost real, benefit hypothetical51
Gavalda [23]Spain2002Two ICUs, total 396 beds12 monthsIntermediateCost–benefit, cost real, benefit hypothetical44
Chaix [24]France1993ICU, total 180 beds, 950 admissionsNot relevantHighCost–benefit88
Keshtgar [25]UK2006Surgical ward + ICU, 9792 admissions12 monthsHighCost-effectiveness36
Jernigan [26]Virginia, USA1986Hospital-wide, 700 beds8 yearsIntermediateCost–benefit, cost real, benefit hypothetical21
Leonhardt [27]Wisconsin, USA2010Hospital-wide, intervention hospital 167 beds, control 700 beds5 monthsLowCost–benefit analyses (cost/benefit ratio)52
Nyman [28]Minneapolis, USA2004ICU, outcomes hospital-wide, 279 beds24 monthsIntermediateCost–benefit, cost real, benefit hypothetical72
Bjorholt [29]Sweden1999Hospital-wide, 2628 beds36 months (results reported for 20, 24 and 36 months)LowCost-effectiveness (cost per colonization averted)77
Herr [30]German1999Septic surgical ward, 13 beds12 monthsHighaCost–benefit, cost real, benefit hypothetical15
Papia [31]Canada1996Hospital-wide, 470 acute-care beds12 monthsIntermediateCost evolution21
Nulens [5]Netherlands2000Hospital-wide, 700 beds5 yearsLowCost evaluation15
Tavolacci [32]France2002Geriatric and rehabilitation, 129 admissions3 monthsHighCost evaluation21
Forward [33]Canada2007Hospital-wide, 21 599 patients21 monthsLowCost evaluation8
Uckay [34]Switzerland2006Internal medicine ward, 246 beds3 monthsHighCost evaluation7
Wassenberg [35]Netherlands200514 hospitals18 monthsLowCost evaluation22
Conterno [36]Canada2004Hospital-wide, 1200 beds6 monthsIntermediateCost evaluation28
Could [37]UK2001ICU, annual admission rate of 780 patients24 monthsHighCost evaluation15
Walsh [38]USA1982Hospital-wide, 291 beds43 monthsOutbreak, highCost evaluation15
Morgan [39]Iowa, USA2007Medical and surgical ICU at 199 bed hospital26 monthsHighEvaluation of cost from published estimates31
Spence [40]Montana, USA2007Hospital-wide, 285 beds4 yearsLowCost evaluation13
Garcia [41]Chicago, USA2008Neonatal-care unit, 20 beds12 monthsHighCost evaluation31
Buhlmann [42]Switzerland2005Hospital-wide, 1000 beds5 monthsIntermediateCost evaluation7
Creamer [43]Ireland20074 wards, about 120 beds4 monthsLowCost evaluation13
Bantar [44]Argentina2000Hospital-wide, 250 beds24 months including 6 first months of base lineHighSaving/benefit evaluation7
Frank [45]Indianapolis, USA1994Hospital-wide, 365 beds12 monthsHighSaving/benefit evaluation28
Geissler [46]Toulon, France1995ICU, 11 beds4 yearsHighSaving/benefit evaluation6
Souweine [47]France1995ICU, 10 bed ICU12 monthsHighSaving/benefit evaluation11
image

Figure 1. Study flow–studies included in qualitative synthesis.

Download figure to PowerPoint

The components of the infection control interventions are detailed in Table 2. A comprehensive ‘search and destroy’ policy [14] was assessed in seven studies, conducted mostly in low endemicity settings in the Netherlands, Belgium, Germany and Sweden. It included screening on admission of patients at risk for MRSA, isolation of patients in single rooms, decolonization and follow-up screening, with variable healthcare worker screening, suspension from work, visitor screening and environmental cultures. Of the 33 (92%) studies assessing patient screening, 20 (55%) also performed decolonization. Decolonization was more commonly used in studies conducted in Europe than in the USA, 16/20 (80%) and 3/20 (15%) studies, respectively. Patients were pre-emptively placed in contact isolation before screening results were available in 12 (36%) of the screening studies. Contact isolation was included in the intervention in 30 (83%) studies. Few studies included cohorting of patients or staff (11 and 7 studies, respectively).

Table 2. Components of infection control interventions in individual studies
Study IDContact isolationCohorting patientsCohorting staffDedicated IC personnelaMonitoring of clinical infectionsPre-emptive isolationScreening with decolonizationScreening without decolonizationAntimicrobial stewardshipEnvironmental culturesCompliance monitoringb
  1. ICU, intensive care unit.

  2. a

    Description in manuscript of personnel (nurse of physician) dedicated to infection control.

  3. b

    Monitoring adherence to infection control interventions.

  4. c

    Staff education was provided only.

Wernitz [13]XX  XXX    
Simoens [14]
ICUX  X XX    
Gerontology unit   X  X    
van Rijen [15]XXXXXXX    
Vriens [16]XXXXXXX    
Rao [17]XX XX X  XX
Nixon [18]X    XX    
West [19]X  XXX X   
Clancy [20]X  X   X   
Knausz [21]X     X  X 
Karchmer [22]X XX   X   
Gavalda [23]X  X  X   X
Chaix [24]XXX   X    
Keshtgar [25]   X  X   X
Jernigan [26]X  XX  X   
Leonhardt [27]X  X X X  X
Nyman [28]X  X   X   
Bjorholt [29]XXXX XX   X
Herr [30]XX    X    
Papia [31]X  X  X   X
Nulens [5]XXXX XX   X
Tavolacci [32]X      X   
Forward [33]       X   
Uckay [34]XX   XX    
Wassenberg [35]X  X XX    
Conterno [36]X  X   X   
Could [37]XX    X    
Walsh [38]XXXXX X  XXc
Morgan [39]       X   
Spence [40]X      X   
Garcia [41]X  X  X    
Buhlmann [42]X      X   
Creamer [43]       X   
Bantar [44]   X    X  
Frank [45]X  XX   X  
Geissler [46]   X    X  
Souweine [47]X  XXXX    

Components of the cost derivation in individual studies are detailed in Table 3. Common cost components included personal protective equipment, personnel time, screening and laboratory materials, and antimicrobials. Costs related to building or renovation of extra rooms needed for isolation and cohorting were reported in a single study [16]. The dominant cost component, when reported, was the loss of bed-days. Save costs were usually expressed as infections or bed-days averted using a global sum for the extra costs of an invasive MRSA infection or per bed-day. A single study considered potential lives saved as benefit, although no formal cost-effectiveness per life-year was performed (15). Only seven (19%) studies used discounting for costs or benefits that went beyond 1 year, five (14%) performed sensitivity analyses for the cost or benefit estimates and these were usually limited to one or few assumptions regarding a single component of the cost estimate and six (17%) studies reported on an incremental analysis. The perspective of the economic analysis in all studies was the hospital, although this was explicitly defined in only nine (25%). None of the studies quantified indirect costs.

Table 3. Cost components included in each studya
Study IDPersonal protective equipmentNurse/Physician timeAntimicrobialsScreening materials (swabs, PCR etc.)Building and/RefurbishmentLaboratory materialsLaboratory personnelTesting, proceduresHospitalization daysGlobal infection costsLife yearsGlobal cost of interventionClosure of wards, operating room
  1. a

    V stands for a component included in the cost derivation and Λ stands for a cost component included in the calculation of savings.

Wernitz [13]VV   V   Λ   
Simoens [14]Λ  VVΛΛ    
van Rijen [15] V   VV  ΛΛ  
Vriens [16]VV VV  VΛ   
Rao [17]ΛVΛ V  VV Λ    
Nixon [18]      ΛΛ  V 
West [19]VV V     Λ   
Clancy [20]VV   V   Λ   
Knausz [21]         Λ V 
Karchmer [22]VV   VV  Λ   
Gavalda [23]VVV  V  Λ    
Chaix [24] V       Λ V 
Keshtgar [25]     V  Λ    
Jernigan [26]VV       Λ   
Leonhardt [27]   V    VΛ   
Nyman [28]VV V VV  Λ   
Bjorholt [29] V   V  VΛ  V
Herr [30]VVVV    VΛ V 
Papia [31]VVV  V  V    
Nulens [5]VVVV    V    
Tavolacci [32]   V         
Forward [33]   V  V      
Uckay [34]   V    V  V 
Wassenberg [35]   V VV V  V 
Conterno [36]VV V  V V   V
Gould [37]  VV         
Walsh [38]  V  VV      
Morgan [39]           V 
Spence [40]VV           
Garcia [41] V V V       
Buhlmann [42]         V V 
Creamer [43]   V         
Bantar [44]  Λ          
Frank [45]  Λ          
Geissler [46]  Λ          
Souweine [47]  Λ          

The median save/cost ratio across all studies reporting both values (18 studies) was US$7.16 (IQR 1.37–16) and the median net global saving was US$23 509 (IQR 3194–50 049) per month. The median cost across all studies reporting intervention costs (31 studies) was US$8648 (IQR 2025–19 170) per month. The median saving across all studies reporting this (23 studies) was US$38 751 (IQR 14 206–75 842) per month. Fifteen of the 18 studies reporting both intervention and save costs (83%) showed that infection control interventions were economically justified because the save/cost ratio was >1 or the save–cost difference was positive (Table 4). Three studies reported a save/cost ratio <1 and negative save-cost difference. In two of them PCR was used for universal patient screening at admission [27] or before surgery [25]. Herr et al. [30] described that implementation of the German Health Authority recommendations for prevention and control of MRSA cost more than the gains of preventing MRSA transmission. Most (80%) of the costs in this study were related to lost bed-days in multi-bed rooms where an MRSA case was isolated.

Table 4. Intervention and saving costs
Study IDStudy size (n patients if given)Total intervention cost per month (in 2011 US$)Total saving cost per month (in 2011 US$)Save/cost ratioaSave–cost difference per month (in 2011 US$)Intervention reported as efficacious
  1. ICU, intensive care unit.

  2. a

    Ratio per month unless otherwise stated.

  3. b

    In these studies different laboratory methods for examining screening samples were compared, including standard cultures, agar gel, standard PCR, Xpert or IDI-GeneOhm commercial real-time PCR essay.

Wernitz [13]539222626 9697.6524 743Y
Simoens [14]Hospital-wide, 1900-bed hospital    Y
ICU 639374541.171061 
Gerontology unit 371743271.16610 
van Rijen [15]Hospital-wide, 1370-bed hospital24 53972 9741.9848 435Y
Vriens [16]Hospital-wide, 1042-bed hospital29 55584 4442.8654 889Y
Rao [17]11 patients and 200 employees958527 43711.4517 852Y
Nixon [18]1796 elective and 1122 trauma patients13 82560 3624.3646 537Y
West [19]5980 patients in one hospital and 1732 patients in a second hospital8048109 16913.59101 121N
Clancy [20]1890 patients392726 2026.6722 275Y
Knausz [21]Hospital-wide, 1400-bed hospital32.843938119.893905NS
Karchmer [22]597 infants1192–152132 02419.0430 833–30 504Y
Gavalda [23]214 screened patients114511 2699.8410 124NS
Chaix [24]26-bed medical ICUNANA8.46–36.83 per patientNAY
Keshtgar [25]7938 patients in a surgical ward and 1854 in ICU52 01747 4980.91−4519Y
Jernigan [26]Hospital-wide, 700-bed hospitalNANANA2474–56 988NS
Leonhardt [27]3255 patients during intervention period (15 049 overall including before and after phases)17 25410 0510.58−7208N
Nyman [28]b8266 patients discharged in 2005    NS
Standard 15 30834 870322.78333 395 
Agar 16 068348 77421.71332 706 
PCR 20 801348 68616.76327 885 
Bjorholt [29]Hospital-wide, 2628 bedsNANANA10380.38Y
Herr [30]NS19 69715 1850.77−4512NS
Papia [31]1742 patients10 963   NR
Nulens [5]22 412 patients admitted per year175 259   NR
Tavolacci [32]126 patients, 129 admissions1345   NR
Forward [33]21 599 patients5019   NR
Uckay [34]b     NS
PCR176 patients screened, 1942 hospital admissions8648    
Agar155 patients screened, 1583 hospital admissions10 537    
Wassenberg [35]b     NS
Agar428 patients1533    
Xpert PCR911 patients19 729    
IDI-GeneOhm PCR853 patients11 211    
Conterno [36]b
Standard10 551 patients89 524    
PCR8528 patients114 172   N
Could [37]1421 patients860   Y
Walsh[38]Hospital-wide, 291 beds, 780 admissions yearly1090   Y
Morgan [39]585 patients2025   NR
Spence [40]6712 patients671   N
Garcia [41]445 infants1049–1517   NS
Buhlmann [42]232 patients, 258 episodes19 170   NR
Creamer [43]      
Universal340 patients3483   NS
Targetted552 patients2213   NS
Bantar [44]116 945 patient-days 46 423  N
Frank [45]Hospital-wide, 13 943 admissions yearly 45 478  Y
Geissler [46]1399 patients 42.23–134.01 per patient  Y
Souweine [47]351 admissions 15.21–23.95 per patient (antibiotic drug only)  Y

Effects of the study characteristics on save/cost ratios and net costs are shown in Table 5. Higher save/cost ratios were observed in an intermediate to high endemicity setting compared with a low-endemicity setting and were highest when the intervention was implemented during an outbreak. Save/cost ratios were higher in smaller hospitals (<500 beds compared with larger hospitals) and with longer intervention duration (>6 months compared with shorter duration). The ‘search and destroy’ policy was associated with lower save/cost ratios than more restricted interventions, as was pre-emptive isolation before culture results compared with no isolation before screening results. Screening without decolonization had higher save/cost ratios than screening with decolonization. The comparison between targeted and universal screening was complicated by the fact that targeted screening was associated with other study characteristics (e.g. screening using PCR).

Table 5. Effect of study characteristics on resultsa
 Intervention cost per month (in 2011 US$)Total saving cost per month (in 2011 US$)Save/cost ratioaSave–cost difference per month (in 2011 US$)
  1. ICU, intensive care unit; QHES, Quality of Health Economic Studies tool.

  2. a

    Median (range) values presented. Studies reporting on costs per patient where the number of patients was not given are not included. n, number of studies; a, number of interventions.

  3. b

    Studies included only when reporting on number of hospital beds (or information available for the study period).

Endemicity
Low4215 (671–175 259), n = 9, a = 1249 972 (10 051–84 444), n = 4, a = 42.42 (0.58–7.65), n = 4, a = 424 743 ((−) 7203–54 889), n = 5, a = 5
Intermediate/High9585 (33–114 172), n = 18, a = 2345 478 (3938–348 686), n = 12, a = 159.84 (0.77–119.89), n = 10, a = 1320 064 ((−) 4519–333 395), n = 11, a = 14
Outbreak1223 (1090–1356(, n = 2, a = 232 024, n = 1, a = 119.04, n = 1, a = 130 833–30 504, n = 1, a = 1
Study years
Last decade9592 (33–114 172), n = 16, a = 2436 850 (3938–348 686), n = 7, a = 105.52 (0.58–119.89), n = 7, a = 1013 090 (610–333 395), n = 7, a = 10
≤20028048 (860–175 259), n = 13, a = 1338 751 (11 269–109 169), n = 10, a = 108.75 (0.77–19.04), n = 8, a = 827 237 ((−) 4519–101 121), n = 10, a = 10
Hospital sizeb
>500 beds19 170 (33–114 172), n = 10, a = 1126 969 (3938–109 169), n = 6, a = 72.86 (1.16–119.89), n = 6, a = 724 743 (610–101 121), n = 8, a = 9
≤500 beds8816 (671–7254), n = 9, a = 1277 796 (10 051–48 686), n = 6, a = 815.18 (0.58–22.78), n = 4, a = 6214 503 ((−) 7203–3395), n = 4, a = 6
Intervention duration
>6 months5019 (33–175 259), n = 19, a = 2345 950 (3937–348 686), n = 12, a = 148.75 (0.77–119.89), n = 10, a = 1227 237 ((−) 4519–333 395), n = 12, a = 14
≤6 months9116 (3717–114 172), n = 10, a = 1418 744 (4326–109 169), n = 5, a = 62.76 (0.58–13.59), n = 5, a = 69456 (610–101 121), n = 5, a = 6
‘Search and destroy’
Implemented12 211 (2226–175 259), n = 7, a = 926 969 (4327–84 444), n = 4, a = 51.98 (1.16–7.65), n = 4, a = 517 561 (610–54 889), n = 5, a = 6
Not implemented8348 (33–114 172), n = 23, a = 2845 478 (3938–348 686), n = 13, a = 1511.45 (0.58–119.89), n = 11, a = 1326 003 ((−) 7.203–333 395), n = 12, a = 14
Pre-culture (pre-emptive) isolation
Included13 825 (2226–175 259), n = 7, a = 743 666 (7454–109 169), n = 6, a = 63.61 (0.58–13.59), n = 6, a = 624 743 ((−) 7203–101 121), n = 7, a = 7
Not included6833 (33–114 172), n = 23, a = 3038 751 (3938–348 686), n = 12, a = 1410.65 (0.77–119.89), n = 10, a = 1222 275 ((−) 4519–333 395), n = 11, a = 13
Screening only versus screening with decolonization
With decolonization9585 (33–175 259), n = 17, a = 2126 969 (3938–84 444), n = 10, a = 112.86 (0.77–119.89), n = 10, a = 1110 252 ((−) 4519–54 889), n = 11, a = 12
Without decolonization6533 (671–114 172), n = 12, a = 16109 169 (10 051–348 686), n = 5, a = 716.76 (0.58–22.78), n = 5, a = 765 895 ((−) 7203–333 395), n = 6, a = 8
Screening by using PCR
With PCR19 170 (671–114 172), n = 8, a = 947 498 (10 051–348 686), n = 3, a = 30.91 (0.58–16.76), n = 3, a = 3(−) 4519 ((−) 7203–327 885), n = 3, a = 3
Other4472 (33–175 259), n = 25, a = 2827 437 (3938–248 774), n = 13, a = 157.65 (0.91–119.89), n = 13, a = 1524 743 ((−) 4519–333 395), n = 15, a = 17
Universal versus targeted screening
Targeted8816 (33–175 259), n = 16, a = 2015 185 (4327–109 169), n = 8, a = 97.65 (1.16–119.89), n = 8, a = 910 124 ((−) 4512–101 121), n = 8, a = 9
Universal8647 (860–52 017), n = 12, a = 1560 362 (10 051–348 774), n = 5, a = 76.76 (0.58–22.78), n = 5, a = 734 406 ((−) 7203–333 395), n = 6, a = 8
QHES score (median = 22)
QHES ≥228048 (33–114 172), n = 15, a = 2132 024 (3938–109 169), n = 12, a = 158.75 (0.91–119.89), n = 11, a = 1422 275 ((−) 4519–101 121), n = 12, a = 15
QHES <229116 (860–175 259), n = 14, a = 1646 423 (15 185–84 444), n = 5, a = 53.61 (0.77–11.45), n = 4, a = 429 731 ((−) 4512–54 889), n = 5, a = 5
Measurement of costs were appropriate
Yes11 087 (1090–175 259), n = 19, a = 2439 761 (10 051–348 686), n = 10, a = 1210.65 (0.58–22.78), n = 10, a = 1226 003 ((−) 7203–333 395), n = 12, a = 14
No37 171 (33–29 556), n = 10, a = 1360 362 (3938–84 444), n = 6, a = 73.61 (1.16–119.89), n = 5, a = 614 324 (610–54 889), n = 5, a = 6

The QHES score ranged between 7 and 77 (median 22). We examined the effect of the total QHES score and one of its variables (question 9), whether measurement of costs was appropriate, on results. Studies with QHES score above the median and appropriate description of cost measurement showed lower absolute cost and save values and higher save/cost ratios than studies with poorer methods of reporting.

None of the studies performed a formal cost-effectiveness analysis to calculate the cost per life-year or per infection prevented. One study reported a cost of US$37 815 per life saved (a patient who would have died in-hospital was discharged alive), for the search and destroy policy in the Netherlands [15]. The clinical effects of the infection control interventions were heterogeneously reported as change in rates of bloodstream infections, other infections and colonization rates, using various numerators (MRSA or all S. aureus) and denominators. Qualitatively, the intervention resulted in a reduction in infection rates in 16 studies and had no effect in five studies (Table 4).

Discussion

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

Most of the published studies show large and significant economic benefit with infection control interventions aimed at preventing MRSA transmission in acute care hospitals. Overall, across all studies included in our review, savings were about seven times higher than costs when an infection control intervention was applied. The absolute gain was more than US$20 000 per month for a single hospital. The balance was even more favourable in intermediate and high MRSA endemicity settings. Higher save/cost ratios were reported in higher quality studies. In the single study considering benefit as life-years saved, a cost of US$37 815 was calculated for the search and destroy policy in the Netherlands per in-hospital death prevented [15]. Considering the extreme scenario of a median survival of 1.5 years for patients discharged alive from hospital following an MRSA bacteraemia [48], this would translate to a cost of US$28 488 per life-year, a figure well within the boundaries of acceptable cost-effectiveness [49-52].

Interventions lasting for more than 6 months were associated with higher gains than shorter interventions. In the long run, investments in comprehensive preventive strategies, including laboratory technologies, construction and trained personnel, repay. Restricted interventions had higher save/cost ratios than more intensive interventions. However, we cannot exclude an association between individual study characteristics, such as restricted interventions reported in long-term studies. We could not conclude on the cost–benefit of screening with PCR. Data in our review were insufficient to compare universal versus targeted screening. In a recent study in Ireland, targeted screening comprised 62% of admissions and identified 92% of colonized patients. Hence, it seems that in some locations risk factors are able to identify a subgroup of patients with sufficient specificity to allow for targeted screening, so reducing screening costs.

Previous systematic reviews examined the clinical effects of infection control interventions for MRSA [53-55]. Cooper et al. [55] included 46 studies published up to 2000. Most of the studies showed reduction in MRSA transmission. The strongest level of evidence came from studies reporting on comprehensive infection control interventions, usually including screening, decolonization and isolation or cohorting. Assessment of the effects of individual interventions and comparison between types of interventions could not be performed. The authors highlighted major methodological weaknesses and inadequate reporting in published research. Regression to the mean occurring when outbreaks of MRSA prompted the intervention was also observed in our economic analysis. Tacconelli et al. [54] focused on screening for MRSA. Qualitatively, of ten studies performed between 2000 and 2007 and included in the review, four reported a significant decrease in MRSA, one showed a decrease only in some wards and five showed no effect. Rapid molecular screening was not associated with a significant reduction in MRSA infection rates compared with standard culture screening. A review attempting to summarize both the clinical and economic impact of infection control measures for MRSA concluded that the economic analysis could not be performed because of study heterogeneity [56].

Several limitations of our analysis should be noted. We restricted our search to fully published articles and could not formally examine for publication bias. Data are reported in the primary studies without confidence intervals or other measures of precision. We did not compute cost-effectiveness estimates although most studies reported on clinical effectiveness. Clinical effectiveness ‘units’ were highly variable including MRSA colonizations, infections, bloodstream or other specific infections prevented. We tried to derive cost and cost–benefit estimates for the individual infection control intervention components. We could address only two components, pre-emptive isolation and decolonization. However, even these subgroup analyses included studies with various combinations of interventions in addition to isolation or decolonization. A small number of studies reported on an isolated intervention of antibiotic stewardship and reported only on intervention costs without examining global savings. All other intervention components were mixed and heterogeneous. We did not attempt to estimate the cost-effectiveness of standard precautions and specifically hand hygiene alone. However, these formed the basis of the more complex interventions addressed in our review.

There are also limitations to the included studies. The hospital settings in which the intervention was conducted were not fully described: the general infection control infrastructure, infection control, clinical microbiology and infectious diseases staffing, microbiology laboratory characteristics, facility or relevant ward design, nurse to patient ratio. All of these are important to understand the external validity of the study and all may affect compliance with study policy (which was stated in eight studies only). However, most or all studies were conducted in settings with a basic infection control infrastructure (e.g. existing infection control expertise, private rooms for contact isolation) and so results are probably mostly relevant to these settings. As for all multidrug-resistant bacteria, MRSA is prone to inexplicable fluctuations in incidence [57]. Existing cost studies did not perform formal time series analyses to show that the reductions in MRSA rates were related to the interventions performed. The cost components considered per intervention and the derivation of costs were highly variable. Sensitivity analyses to examine different aspects of the intervention or benefit were rarely conducted. All studies focused on the perspective of the hospital, without considering costs and benefit after patients’ discharge and indirect costs, such as productivity losses. Formal cost–benefit analyses were rarely conducted.

In conclusion, infection control interventions reported in the available literature usually show highly favourable cost–benefit calculations. This is true also for high MRSA endemicity settings. Unresolved economic issues include rapid screening using molecular techniques and universal versus targeted screening. There is a need for guidance on how to conduct and report economic analyses of infection control interventions in primary studies that will allow for comparison between studies and increase the external validity of individual studies.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

This study was completed in partial fulfilment of Laura Farbman's Master in of Health Administration in The Health Administration Program—an innovative joint endeavour of the Faculty of Management and the Faculty of Medicine at Tel-Aviv University.

Funding

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

Laura Farbman's work was funded by a grant from the Caesarea Foundation and a scholarship from The Israel National Institute for Health Policy and Health Services Research (NIPH). The sponsors played no role in study planning, design, conduct, analysis, interpretation of data; writing of the report or in the decision to submit the article for publication.

Author Contributions

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

LF, LL, BR and MP were responsible for conception and design. LF, TA and MP searched for and retrieved articles and extracted and analysed data. LF, LL and MP were responsible for interpretation and writing. LL and BR critically revised the manuscript, which was approved by all authors.

References

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review
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Appendix 1: Search clause

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review
 
#1: MRSA OR methicillin-resist* OR ‘Methicillin-Resistant Staphylococcus aureus’[Mesh].
#2: Surveillance OR screening OR monitoring OR decolonization.
#3: Contact-isolation OR patient-isolation OR contact-precautions OR cohorting OR single-room OR gown* OR antimicrobial-stewardship OR antibiotic-stewardship OR (antibiotic AND restriction) OR (antibiotic AND approval) OR antibiotic-guideline* OR (antibiotic AND streamline*) OR (antibiotic AND cycling).
#4: #2 OR #3.
#5: #1 AND #4.
#6: Cost OR costs OR cost-effectiveness OR cost-benefit OR cost-utility OR cost-minimization OR ‘Economics’[Mesh] OR ‘Economics, Hospital’[Mesh] OR ‘Costs and Cost Analysis’[Mesh] OR ‘Cost-Benefit Analysis’[Mesh] OR ‘Cost Control’[Mesh] OR ‘Health Care Costs’[Mesh] OR ‘Direct Service Costs’[Mesh] OR ‘Hospital Costs’[Mesh].
#7: #5 AND #6.

Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review

  1. Top of page
  2. Abstract
  3. Background
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Funding
  9. Author Contributions
  10. Transparency Declaration
  11. References
  12. Appendix 1: Search clause
  13. Appendix 2: The Quality of Health Economic Studies (QHES) instrument adapted for our review
 QuestionUsed in adapted QHES aScore
  1. a

    The QHES instrument contains 16 dichotomous (Yes/No) items, each weighted by its importance as determined by an expert panel of health economists. The maximal score is 100 and the quality score is calculated by subtracting points from 100 for questions answered with No. We omitted several items from our quality assessment, because we included primary studies rather than cost-effectiveness models. N – not used in our review, C – used for studies describing costs alone, T – used for studies describing cost-effectiveness or cost–benefit. Hence, the maximal score for studies describing costs alone was 50 and for studies describing cost-effectiveness or cost–benefit was 86.

1Was the study objective presented in a clear, specific and measurable manner?C,T7
2Were the perspective of the analysis (e.g. societal, third-party payer) and reasons for its selection stated?C,T4
3Were variable estimates used in the analysis from the best available source (i.e. randomized controlled trial—best; expert opinion—worst)?N8
4If estimates came from a subgroup analysis, were the groups pre-specified at the beginning of the study?N1
5Was uncertainty handled by: (i) statistical analysis to address random events; (ii) sensitivity analysis to cover a range of assumptions?C,T9
6Was incremental analysis performed between alternatives for resources and costs?C,T6
7Was the methodology for data abstraction (including the value of health states and other benefits) stated?N5
8Did the analytic horizon allow time for all relevant and important outcomes? Were benefits and costs that went beyond 1 year discounted (3–5%) and justification given for the discount rate?C,T7
9Was the measurement of costs appropriate and the methodology for the estimation of quantities and unit costs clearly described?C,T8
10Were the primary outcome measure(s) for the economic evaluation clearly stated, and were the major short-term, long-term and negative outcomes included?T6
11Were the health-outcome measures/scales valid and reliable? If previously tested valid and reliable measures were not available, was justification given for the measures/scales used?T7
12Were the economic model (including structure), study methods and analysis, and the components of the numerator and denominator displayed in a clear, transparent manner?T8
13Were the choice of economic model, main assumptions and limitations of the study stated and justified?T7
14Did the author(s) explicitly discuss direction and magnitude of potential biases?C,T6
15Were the conclusions/recommendations of the study justified and based on the study results?T8
16Was there a statement disclosing the source of funding for the study?C,T3
 Total 100