Announcements
Eurosurveillance remains in the updated list of the Directory of Open Access Journals (DOAJ). It was first added to the DOAJ on 9 September 2004. Eurosurveillance is also listed in the Securing a Hybrid Environment for Research Preservation and Access / Rights MEtadata for Open archiving (SHERPA/RoMEO) [2], a database which uses a colour‐coding scheme to classify publishers according to their self‐archiving policy and to show the copyright and open access self-archiving policies of academic journals. Eurosurveillance is listed there as a ‘green’ journal, which means that authors can archive pre-print (i.e. pre-refereeing), post-print (i.e. final draft post-refereeing) and archive the publisher's version/PDF.

ESCAIDE participants are invited to the fifth Eurosurveillance scientific seminar on 30 November 2016

Follow Eurosurveillance on Twitter: @Eurosurveillanc

Read our articles on Zika virus infection

Note of concern published for 'Epidemiological investigation of MERS-CoV spread in a single hospital in South Korea, May to June 2015', http://bit.ly/29QFXPp


In this issue


Home Eurosurveillance Edition  2014: Volume 19/ Issue 29 Article 4
Back to Table of Contents
Previous Download (pdf)
Next

Eurosurveillance, Volume 19, Issue 29, 24 July 2014
Review articles
Systematic literature analysis and review of targeted preventive measures to limit healthcare-associated infections by meticillin-resistant Staphylococcus aureus
  1. Institute of Hygiene, University Hospital Münster, Münster, Germany
  2. Institute of Medical Microbiology, University Hospital Münster, Münster, Germany
  3. Division of lnfection and lmmunity, University College London, London, United Kingdom
  4. Faculty of Behavioural Sciences, University of Twente, Enschede, the Netherlands
  5. Infection Control Program, University of Geneva Hospitals and Medical School, Geneva, Switzerland
  6. Department of Medical Microbiology and Infection Control, VU University Medical Centre, Amsterdam and Amphia Hospital Molengracht, Breda, the Netherlands
  7. Robert Koch Institute, Department for Infectious Diseases, Berlin, Germany
  8. Department for Microbiology and Infection Control for Microbiological Surveillance and Research, Statens Serum Institut, Copenhagen, Denmark
  9. European Centre for Disease Prevention and Control, Stockholm, Sweden
  10. Division of Infectious Diseases, Department of Internal Medicine I, University Hospital Tübingen, Tübingen, Germany
  11. Robert Koch Institute, Reference Centre for Staphylococci, Wernigerode, Germany
  12. Department of Medical Microbiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

Citation style for this article: Köck R, Becker K, Cookson B, van Gemert-Pijnen JE, Harbarth S, Kluytmans J, Mielke M, Peters G, Skov RL, Struelens MJ, Tacconelli E, Witte W, Friedrich AW. Systematic literature analysis and review of targeted preventive measures to limit healthcare-associated infections by meticillin-resistant Staphylococcus aureus . Euro Surveill. 2014;19(29):pii=20860. Article DOI: http://dx.doi.org/10.2807/1560-7917.ES2014.19.29.20860
Date of submission: 20 April 2013

Meticillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections in Europe. Many examples have demonstrated that the spread of MRSA within healthcare settings can be reduced by targeted infection control measures. The aim of this systematic literature analysis and review was to summarise the evidence for the use of bacterial cultures for active surveillance the benefit of rapid screening tests, as well as the use of decolonisation therapies and different types of isolation measures. We included 83 studies published between 2000 and 2012. Although the studies reported good evidence supporting the role of active surveillance followed by decolonisation therapy, the effectiveness of single-room isolation was mostly shown in non-controlled studies, which should inspire further research regarding this issue. Overall, this review highlighted that when planning the implementation of preventive interventions, there is a need to consider the prevalence of MRSA, the incidence of infections, the competing effect of standard control measures (e.g. hand hygiene) and the likelihood of transmission in the respective settings of implementation.


Background

Meticillin-resistant Staphylococcus aureus (MRSA) is a major cause of healthcare-associated infections in Europe. In 2008, the European Centre for Disease Prevention and Control (ECDC) estimated that a total number of 171,200 nosocomial MRSA infections are acquired annually in the Member States of the European Union (EU), and in Iceland and Norway, resulting in 5,400 attributable excess deaths, more than 1 million excess days of hospitalisation and EUR 380 million excess in-hospital costs [1]. The burden of MRSA infections was also shown in an analysis of data on healthcare-associated infections collected prospectively from European intensive care units (ICU) between 2005 and 2008, where 1.7% of all patients developed S. aureus pneumonia or bloodstream infections. A mean of 35% of these infections were caused by MRSA. Moreover, the hazard ratio for mortality was 5.6-times higher (95% confidence interval (CI): 3.4–9.4) for patients with MRSA bloodstream infection than for patients without S. aureus bacteraemia [2].

Among the proposed methods to prevent MRSA, many (e.g. hand hygiene and transmission-based precautions) have been used for general infection control, and their effectiveness has been reviewed extensively [3,4]. However, there is an ongoing discussion about the evidence for the effectiveness of several more specific prevention methods which, nevertheless, have been included in standards for the prevention and control of MRSA in a majority of European countries [5]. Therefore, the scope of this review was to analyse systematically recent literature (published after 2000) with respect to the following questions related to MRSA prevention and control:

  1. Does screening of patients before or on admission reduce the incidence of MRSA infection or transmission? How do PCR-based rapid tests for the direct detection of MRSA from screening specimens influence the incidence of MRSA colonisation or infection compared with culture-based methods?
  2. Does the decolonisation of nasal MRSA or S. aureus carriage using mupirocin nasal ointment, alone or in combination with other agents, reduce colonisation or the development of infections?
  3. Does isolation in single rooms of patients colonised or infected with MRSA prevent the spread of MRSA better than the use of transmission-based precautions (hand hygiene, gloves, aprons) alone? What is the effect of pre-emptive isolation of risk patients for MRSA carriage (until screening results are available)?

Methods

A systematic literature analysis and review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [6]. To identify relevant publications, PubMed, EMBASE and Scopus were searched for articles published between 1 January 2000 and 31 October 2012 in English language. The search terms were: MRSA AND (prevention OR control OR prophylaxis OR preventive measures OR preventive therapy OR preventive treatment OR precaution OR screening OR active surveillance OR decolonization OR mupirocin OR surveillance culture* OR chromogenic OR PCR OR polymerase chain reaction OR rapid test OR isolation OR hygiene OR efficien* OR effective*) AND (healthcare OR hospital OR nursing home OR long-term care facilit*); the search terms were adapted for search in EMBASE: “MRSA AND decolonization”, “MRSA AND isolation”, “MRSA AND screening”.

Titles and abstracts were screened independently by two reviewers (RK and AWF). Studies with outcomes measuring the incidence of MRSA colonisation or infection were included. Exclusion criteria were: Studies that did not report on the effects of the preventive measures on infection or transmission; studies performed in settings other than hospitals, long-term care facilities and nursing homes; case series, outbreak reports and reviews (the literature lists of the reviews were manually screened for additional relevant publications).

Data were extracted by AWF and RK independently using a standardised form. The study designs were assigned according to a modified study design scheme published by the Centre for Reviews and Dissemination at the University of York, United Kingdom, in the NHS economic evaluation database handbook from 2007. Formal assessment of the quality of studies was not performed. Due to the different study outcomes included, formal meta-analysis was considered inappropriate. Heterogeneity in methodology and outcome measures also prevented quantitative assessment of publication bias.

Results

The literature search identified 9,340 articles, 151 of which were retrieved as full texts after review of titles and abstracts. Of these, 69 articles fulfilled the criteria for inclusion and a further 14 articles were added after search through the literature lists of excluded review articles (Figure). Overall, 83 articles were included in the review [7-89].

Figure. Flow diagram for the selection of studies on preventive measures against to limit healthcare-associated infections by meticillin-resistant Staphylococcus aureus, published 2000–2012 (n=9,340)

        
 
Screening
We identified 41 studies that investigated the question whether screening for MRSA carriers before or on admission had an impact on MRSA acquisition or infection rates (Table 1) [7-47].

Culture-based screening
Twenty-five studies used culture-based screening approaches, including two randomised controlled trials (RCTs) and 23 comparative studies mostly using a before-and-after design [9,10,12,15,19-21,27,28,30-38,40,42-47]. Of these 25 studies, seven used unspecified culture-based techniques [12,21,27,28,37,40,46], eight used MRSA chromogenic media (at least partially) [19,31-34,38,45,47] and the others used mannitol salt, oxacillin salt or blood agars. An estimate for the turnaround times (TAT) of screening results was only reported in eight of the 25 studies (1 d–5.2 d) [10,12,19-21,33,34,38]. Overall, 19 of the 23 comparative studies included reported trends of decreasing rates of MRSA infection or colonisation [10,12,15,19,21,27,28,30-32,35-38,40,42,43,45,46], two reported ambiguous results [44,47], and two reported no reduction of MRSA infections or transmission [33,34]. The two RCTs found no reduction of MRSA infections or transmission [9,20].

PCR-based screening
Sixteen studies used PCR-based screening techniques in their intervention phases, including one RCT, two prospective cohort studies and 13 comparative studies [7,8,11,13,14,16-18,22-26,29,39,41]. The TAT of the PCR screening result was reported in 11 of 16 studies (0.67 d–1.5 d) [7,11,13,14,16-18,23,25,26,29]. Overall, seven of 16 studies documented positive effects on the occurrence of MRSA infections or transmissions after implementation of screening [8,11,14,18,24,26,29]. One study reported ambiguous results [16]. Among the studies reporting a decrease of infection or transmission, five compared the intervention group (PCR-based screening) to a control group without active surveillance, with non-compulsory active surveillance or with screening of limited risk groups [8,11,24,26,29], and two compared with a control group where routine culture-based screening was performed [14,18]. Among the eight studies which could not document decreasing trends in MRSA infections or transmission following the implementation of screening, three compared PCR-based screening with culture-based screening [7,13,23], four compared the intervention to control periods without any active surveillance of MRSA [17,22,39,41], and one compared the intervention with a baseline period where PCR-based screening of selected risk patients was performed [25].

Screening (PCR-based and culture-based) vs no screening stratified by outcome measure
In eight of nine studies (89%) using this outcome parameter, MRSA bacteraemia rates decreased after implementation of screening [8,11,21,26,28,31,32,38,47]. Incidence of MRSA acquisition or transmission decreased in three of eight studies (38%) assessing this outcome parameter [8,9,17,32-34,43,44]. Three of five studies (60%) using wound infection and surgical-site infections (SSI) as an outcome parameter showed decreasing SSI rates after implementation of screening [8,17,24,37,39]. A decrease of MRSA was observed in 20 of 23 studies (87%) using all or unspecified MRSA infections or cases of colonisation/infection as their outcome parameters [8-10,12,15-17,19,20,22,25-27, 29,30,35,36,40-42,45-47]; among these studies, one found a decrease only in medical ICUs [16].

PCR-based vs culture-based screening
Five investigations compared PCR-based to culture-based screening [7,13,14,18,23]. All five documented that the TAT was reduced when compared to culture-based approaches (Table 1). However, three studies found no difference in MRSA acquisition or infection rates [7,13,23]. In contrast, one before-and-after study found a reduction in the incidence of MRSA transmission after introduction of the PCR-based test which almost reached statistical significance, and one cohort study reported a reduction in MRSA acquisition rates [14,18].

Table 1. Studies on the effectiveness of the use of active surveillance (screening) for meticillin-resistant Staphylococcus aureus, published 2000–2012 (n=41)

                   

            
       

Decolonisation
A total of 11 RCTs, 23 comparative studies and one prospective cohort study evaluated the effectiveness of mupirocin-based nasal decontamination regimens for the prevention of S. aureus infections (Table 2) [48-82]. Of all 11 RCTs, six demonstrated significantly decreasing infection trends after implementation of decolonisation [48,51,52,72,73,75]; for one of these, this was only observed when selective digestive decontamination was added to nasal decolonisation [52], and for one RCT, the effect was only analysed for Gram-positive infections (which were mostly MRSA) [75]. Stratified by types on infections prevented, the RCTs showed that decolonisation decreased deep S. aureus SSI [48], overall S. aureus infections [48,51,73], overall infection rates [52], Gram-positive pneumonia [75] and S. aureus exit-site infections [72].

Among the 24 non-randomised studies identified, 19 reported evidence that the use of mupirocin was effective in reducing infection. Of the seven studies performed in ICUs, six (86%) demonstrated an effect; specifically, a decrease in pneumonia and hospital-acquired S. aureus infection [59], in the overall infection rates in ICUs [50,70], in MRSA SSI and bloodstream infections (BSI) in ICUs [55], and in the overall number of MRSA infections in ICUs [80,81]. Non-controlled studies implementing decolonisation in non-ICU settings led to a decrease in overall and peristomal MRSA infections [57,76], in the incidence of S.aureus/MRSA SSI in surgical units [55,58,64,65,71,77,79], in overall S. aureus/MRSA infections in gastrointestinal surgery and orthopaedics [49,82], and in the total rate of SSI or wound infections [53,60,67].

Stratified by different implementation settings, four of five studies documented success among patients undergoing cardiothoracic surgery [53,65,66,71,77], four of six in orthopaedic departments [49,60,61,63,64,79], and six of seven in other or mixed surgical departments [54,55,58,67,73,75,82]. Moreover, seven of eight studies performed in ICU settings [50,52,55,59,68,70,80,81], two of two performed in haemodialysis units [51,72], two of five performed in different non-surgical departments [56,57,69,76,78], and one of three studies performed hospital-wide or in both medical and surgical departments [48,62,74], demonstrated successful effects of mupirocin-treatment.

Stratified by different causative organisms, eight studies showed that mupirocin-treatment led to a decrease in the overall incidence of infections due to all organisms [49,53,60,64,65,67,70,77]. In the same studies, this effect was partially non-significant for S. aureus/MRSA infections in particular [53,60,67,70]. Four studies reported a decrease in infections caused by methicillin-sensitive S. aureus (MSSA) [48,51,55,65]. Twelve investigations revealed a reduction in MRSA infections [49,50,55,57,58,64,76,77,79-82], six showed decreasing trends for S. aureus (MRSA and/or MSSA) infections [50,59,71-73,82] and one reported reduction of pneumonia caused by Gram-positive bacteria (mostly MRSA) [75].

Many of the studies identified in this review used mupirocin-only regimens [51,55,59,60,63,67,70-73,75,78,82]. Others combined nasal mupirocin with other topical agents to support decolonisation, including chlorhexidine [48,50,53,56-58,61,62,64-68,74,81], triclosan [49,76,79], extra-nasal use of mupirocin [69,77,80], selective digestive decontamination [52], povidone-iodine [49], and systemic antibiotics [54].

Table 2. Studies on the effectiveness of Staphylococcus aureus decolonisation using mupirocin-based regimens, published 2000–2012 (n=35)

                
      

Isolation
Focusing on the physical isolation of patients in separate single or cohort rooms, we identified one cohort study and seven comparative studies reporting on the effectiveness of this measure (Table 3) [16,83-89]. Five studies were performed in ICU settings [16,83-85,88], one in a vascular surgery ward, one in a diabetic food unit, and one hospital-wide [86,87,89]. In two of these studies, nurse cohorting was performed in addition to single-room isolation [83,86]. Overall, one cohort and three comparative studies reported on beneficial effects of single-room isolation (not performed pre-emptively) on MRSA colonisation or infection [85,86,88] and on acquisition rates [84]. Two comparative studies did not find a reduction of transmission [83] or MRSA prevalence [87].

Three studies assessed the role of pre-emptive isolation measures pending the results of screening [16,86,89]. In one before-and-after study, pre-emptive isolation precautions led to a reduction of the MRSA acquisition rate (0.21% vs 0.07%; p=0.04) [89]. In a retrospective comparative study placing all admitted patients in pre-emptive isolation, the number of nosocomial MRSA isolates was reduced (p=0.005). However, simultaneous introduction of a cohort isolation facility with dedicated staff makes the effects of this measure indistinguishable from the effects of pre-emptive isolation [86]. The third was a study that evaluated the effects of simultaneous implementation of pre-emptive isolation and a rapid screening test on the incidence of MRSA infections in two ICUs [16] resulting in a significant reduction of ICU-acquired infections in a medical but not in a surgical ICU.

Table 3. Studies on the effectiveness of isolation measures against meticillin-resistant Staphylococcus aureus, published 2000–2012 (n=8)

   

Discussion

Improving the rational use of antibiotics and the implementation of hand hygiene are clearly cornerstones of MRSA prevention and control [90-92]. Moreover, benchmarking and public reporting systems have recently been demonstrated to successfully support infection control measures [93]. However, the effectiveness of screening, decolonisation and isolation for MRSA prevention when implemented routinely in settings with endemic MRSA, remains controversial. For example, it is debated to what extent microbiological, strain-specific factors have contributed to the decreasing MRSA trends [94,95]. Therefore, the present review aimed to focus on three important measures and to summarise the current evidence for their impact on MRSA prevention.

Screening
The strategy of screening is based on the finding that microbiological cultures performed for clinical reasons fail to detect previously unknown MRSA carriers at admission in 69 to 85% of patients [96,97]. Technically, screening can be performed by culture-based methods (screening swab streaked onto non-selective or chromogenic media) or PCR-based tests.

Screening vs no screening
Of 36 cohort and comparative studies investigating the effectiveness of compulsory screening compared with no or non-compulsory screening, 27 reported decreasing trends in the rates of MRSA infection or acquisition; this is in accordance with a meta-analysis describing a decrease in MRSA bloodstream infections (relative risk (RR): 0.54; 95% CI: 0.41–0.71) and surgical site infections (RR: 0.69; 95% CI: 0.46–1.01) [98]. On the other hand, two RCTs found that MRSA acquisition or infection in the intervention groups did not differ significantly from the control groups [9,20]. However, in both studies, the median time for reporting a positive screening result was very long (3 days and 5.2±1.4 days), which led to delayed implementation of contact precautions. In addition, compliance with transmission-based precautions was not as required [20] and the prevalence of MRSA infection was low in one of the studies [9]. Comparing successful and unsuccessful interventions, we did not find clear differences between the studies regarding the specimens used for screening (nasal swab only vs other swabs in addition) or the patient population included (all patients admitted vs high-risk patients only).

There was a tendency that studies including ‘incidence of MRSA acquisition’ as an outcome parameter, reported a success less frequently (three of eight studies) compared with studies focusing on MRSA infection rates using the outcome parameters ‘occurrence of bacteraemia’ (eight of nine studies) or ‘SSI’ (three of five studies). The reason for this effect is not known, but it could highlight that screening does not necessarily affect the rate of cross-transmission on the ward, unless it is linked to additional preventive measures; decolonisation, for instance, was not performed in two of the the studies measuring incidence of acquisition [33,34], while in two others, single-room isolation was omitted or only performed if available [9,17].
                                                
In conclusion, we found evidence that screening can help decrease MRSA infection rates in hospitals. This is also supported by macro-epidemiological data and mathematical models showing that without screening, other infection control measures might fail to effectively reduce MRSA spread [99-102]. However, the included RCTs did not confirm the findings of non-controlled studies. This makes it impossible to firmly recommend the implementation of screening in all settings. However, the evidence provided can support the introduction of a programme for active surveillance of MRSA in settings that have hyperendemic MRSA cross-infections in spite of a high level of compliance with standard precautions. Clearly, the implementation of screening needs to be linked to other targeted infection control measures (e.g. hand hygiene) to achieve optimal impact.

Culture-based screening vs PCR-based screening
Screening for MRSA colonisation of patients at admission using culture-based approaches requires 24 to 72 hours until the results are available on the wards [103,104]. During this time MRSA can spread among inpatients. Therefore, various PCR-based methods have been developed to reduce the TAT [105,106]. Reduction of TAT was indeed confirmed by all studies on PCR-based tests identified in this review. But these studies mostly did not find a significant reduction of MRSA infection or acquisition rates. These results are in accordance with data from a meta-analysis showing that, compared with cultures, the use of rapid tests was not associated with a significant decrease in MRSA acquisition rates (risk ratio 0.87; 95% CI: 0.61–1.24) [98]. On the other hand, we found two studies reporting on a significant reduction of MRSA acquisition and a trend towards declining transmission [14,18]. They demonstrate that implementation of PCR-based surveillance can be beneficial at least in facilities where culture results have a very long TAT (>3 days) [14,18].

We conclude that in settings where MRSA screening based on cultures, followed by the implementation of additional precautions, is already implemented, the current evidence does not suggest replacing or supplementing culture-based surveillance with rapid tests. However, besides accelerating the implementation of additional precautions, the high negative predictive value of MRSA rapid tests may also be useful when discontinuing contact precautions (including single-room isolation) in settings where they are implemented pre-emptively for suspected MRSA carriers [103]. However, the reliability of a negative nasal rapid test has not been evaluated in situations where pre-emptive isolation is performed for high-risk patients, who are often carrying MRSA at extranasal sites (e.g. wounds). Furthermore, using rapid tests in low prevalence settings may increase the number of false-positive tests (positive predictive values: 31–78%) [103,107-110].

Decolonisation
The effectiveness of mupirocin nasal ointment to eradicate MRSA has been estimated to be 94% one week after treatment and 65% after a 14-day follow-up period [111,112]. Effectiveness of MRSA decolonisation therapy is obviously limited when extranasal sites are colonised [113]. Since nasal carriage of S. aureus is a major risk factor for subsequent nosocomial infection, there is a theoretical rationale that eradicating S. aureus from the nares can reduce the development of infection. It is, however, controversial to what extent studies assessing the effectiveness of decolonisation among patients carrying MSSA also hold lessons for MRSA [114]. In this review, we have identified only four studies in which mupirocin-treatment was not restricted to MRSA carriers and where effects on MRSA and MSSA infections were reported separately. All four documented a decrease in MRSA, but found insignificant results for MSSA [64,77,79,82]. However, this does not mean that mupirocin-based decolonisation is ineffective against MSSA in general, since two randomised trials have reported a reduction of MSSA infections [48,51]. The reasons for this discrepancy are unknown, and the question whether results obtained for MSSA can be transferred to MRSA is unresolved. Despite potential local differences in mupirocin susceptibility and the occurrence of clonal lineages [114], a plausible biological explanation why results on MSSA decolonisation treatment should not be applied for MRSA, is currently lacking. Therefore, we have explicitly included studies dealing with S. aureus decolonisation. However, future studies will have to assess in detail the differences between the preventive effectiveness of MSSA and MRSA decolonisation.

Regarding the setting of implementation, we found that 14 of 18 studies carried out mostly in surgical settings have found a reduction in infection rates, whereas six of 10 studies which did not report effectiveness, were performed mostly in non-surgical settings [56,62,68,69,74,78]. However, preventive effects have been documented for non-surgical patients, e.g. in haemodialysis units, ICUs or in gastroenterology [50,51,55,57,59,68,70,72,76,81].

Overall, we conclude that, taking into account local rates of healthcare-associated infections and infection control conditions, mupirocin-based decolonisation therapy should be considered for selected S. aureus carriers who are at high risk of developing nosocomial S. aureus infections. The best evidence is available for patients undergoing cardiothoracic or orthopaedic surgery. Of note, the preventive use of mupirocin for decolonisation is constrained by the development of resistance, found in 1% of all subjects when mupirocin was used for short-term prophylaxis. Increasing low-level mupirocin resistance (8–256 µg/mL) has recently been reported in parallel to increased mupirocin consumption [112,115,116].

Isolation
There are multiple approaches to organise isolation measures: Patients can be transferred to special isolation wards, housed in nursing cohorts with designated staff, isolated in single or cohort rooms on general wards without designated personnel, or housed in the same room as patients not affected by MRSA while applying barrier precautions (e.g. gloves and gowns) when caring for the MRSA patient. In this review, we focussed on single room or cohort room isolation because this measure is sometimes debated as it can be associated with disadvantages for the isolated patient [117]. Moreover, in settings with a high prevalence of MRSA, isolation of patients may be hindered due to insufficient side room capacity and financial constraints, if isolation results in bed-blocking.

Overall, we found four studies showing that single room isolation led to a reduction in nosocomial MRSA acquisition and in the incidence of MRSA infection [84-86,88]. In contrast, in a prospective interrupted-time-series study it was found that, MRSA acquisition was not different in phases during which MRSA-colonised or infected patients were moved to single or cohort isolation, compared with phases during which they were not moved [83]. However, limitations of this study are delayed notification of screening results, a high number of missed screenings (80–87% of patients at admission and 71–75% at discharge) and low compliance with hand hygiene (21% compliance) [83]. Moreover, a retrospective comparative study showed that discontinuing single-room isolation and applying transmission-based precautions (e.g. masks, gowns, gloves) for MRSA patients did not lead to an increase in the prevalence of MRSA. However, that study did not measure the occurrence of transmission on the wards and the incidence of MRSA infections [87].

We conclude that the limited evidence from non-controlled studies which is available to support the use of single-room isolation for MRSA (outside of outbreaks) should inspire further research in this field to facilitate the development of evidence-based guidance in future, also for the prevention and control of other multidrug-resistant organisms. However, the majority of studies identified and observations made during outbreaks support the use of single-rooms [3]. Therefore, where facilities (isolation wards, single rooms, cohort rooms) for the isolation of MRSA patients are available, their use should be recommended.

In all investigations identified, it is difficult to estimate to what extent the observed preventive effects were attributable to pre-emptive isolation or to other measures implemented in parallel [16,86,89]. Consequently, there is a need to assess the evidence for the use of pre-emptive isolation measures in hospitals. This is of major importance, because authors evaluating PCR-based screening tests often suggested that rapid tests could accelerate the start of isolation precautions [16,103,118]. However, these advantages cannot be assessed adequately as long as the additional value of pre-emptive isolation is unclear.

Conclusion

We have documented that the evidence for the effectiveness of three major MRSA prevention and control measures does not allow for clear guidance offering ‘one-size-fits-all’ solutions, because the effectiveness of these interventions seems highly depending on the prevalence of MRSA, compliance with general infection control measures (e.g. hand hygiene), the incidence and type of infections and the transmission rates within the respective setting of implementation. This is documented by the ambiguous study results presented here. In addition, models on the effectiveness of MRSA prevention strategies in different settings have shown that even measures which are performed highly effectively in outbreaks or low-prevalence areas, failed to control MRSA when applied for long-term control or in high-prevalence settings [119]. These difficulties have led to the development of models describing the effects and costs associated with universal vs selective MRSA screening in different settings, which may facilitate the implementation of local standards [104,120]. Moreover, some authors have recently described the effectiveness of several preventive bundles comprising the measures reviewed here in combination with other interventions. For example, it was shown that universal nasal screening, contact precautions for patients colonised or infected with MRSA, hand hygiene, and changes in the institutional culture of responsibility reduced MRSA infections by 62% [99]. Others have identified that structural factors such as engaging front-line staff, building multidisciplinary teams, providing monitoring and feedback, and acquiring management support were key measures for the success of MRSA prevention [121]. The evaluation of such bundles with respect to their effects, feasibility and applicability in different healthcare systems (e.g. different countries), clinical departments and patient collectives could in the future guide preventive efforts. Compared to assessing the effects of single preventive measures separately (as done in this review), the main advantage of assessing the effects of bundles is that they are planned specifically for targeted healthcare sectors, and the assessment can take into account the financial and other structural conditions in the respective settings.

In this review, we did not restrict the eligibility criteria to controlled studies such as RCTs, although quasi-experimental study designs are prone to be associated with various biases (e.g. selection bias or size of study population). This was done because only very few controlled investigations have been published. In addition, among the 14 RCTs included, most of which were performed for assessing the effectiveness of decolonisation therapy, a majority did either include patients affected by MSSA or did not stratify their outcomes for MSSA and MRSA infections. This makes the results, even of these formally ‘high-quality’ studies, disputable. Against this background, we decided not to perform a formal grading of the quality of the included studies, but rather to present the study results holistically and leave their use in various settings and countries open for interpretation.

The controversy about different implementation pathways for screening, isolation and decolonisation should not obscure the fact that the beneficial effects of MRSA control measures in general [120] support the recommendations made in many European national MRSA policies from low prevalence countries (e.g. the Nordic countries and the Netherlands) and high prevalence countries (e.g. France, Germany, and the United Kingdom), where a combination of these measures are the standard of care and a reduction in MRSA infections has recently been achieved by coordinated efforts even in high prevalence settings [5,122].


Acknowledgements
The European Centre for Disease Prevention and Control (ECDC) has funded this work (service contract No. ECD.1366).

Conflict of interest
SH is member of the speakers’ bureau for bioMérieux and Pfizer, the scientific advisory board of Destiny Pharma, DaVolterra and bioMérieux. RLS is member of the Novartis advisory board. AWF has received fees from Siemens, Boehringer Ingelheim and Bayer; RLS from Pfizer, Leo Pharma, RibXrom and The Medicines Company; BDC from Sanofi Pasteur, Pfizer, Esoform/Ecolab and Vemacare.
Financial support for MRSA research activities was provided for: SH from Geneva University Hospitals, B. Braun, Pfizer and the European Commission under the Life Science Health Priority of the 6th Framework Program (MOSAR network contract LSHP-CT-2007-037941); ET from the Italian Department of Culture, University and Research, Università Cattolica Rome, Novartis, Pfizer and the European Commission under the Life Science Health Priority of the 7th Framework Program (SATURN network contract N°241796); KB and RK from the German Federal Ministry of Education and Research (01KI1014A; AFR 10/P12); KB, RK and AWF for the EU-funded Interreg IVa projects EurSafety Heath-net (III-1-02=73) and SafeGuard (III-2-03=025); KB from the German Federal Ministry of Economics and Technology (KF2279801AJ9) and Pfizer (Europe ASPIRE); RLS from the 7th Framework Program (PiiGrim) and from the Danish Ministry of Food, agriculture and Fisheries; and BDC from the English Department of Health. GP, JEWCvGP, JK, MJS, MM, and WW have no conflicts of interest related to this article.

Authors’ contributions
RK and AWF did the literature search and screened titles and abstracts for relevant articles. RK and AWF extracted data from the full-texts. RK, AWF, KB, BC, JEvGP, SH, JK, MM, GP, RLS, MJS, ET and WW contributed to data collection, formulating the conclusions and writing of the manuscript.


References
  1. European Centre for Disease Prevention and Control (ECDC)/ European Medicines Agency (EMEA) joint technical report: The bacterial challenge: time to react. Stockholm: ECDC; 2009. Available from: http://www.ecdc.europa.eu/en/publications/Publications/0909_TER_The_Bacterial_Challenge_Time_to_React.pdf
  2. Wolkewitz M, Frank U, Philips G, Schumacher M, Davey P. Mortality associated with in-hospital bacteraemia caused by Staphylococcus aureus: a multistate analysis with follow-up beyond hospital discharge. J Antimicrob Chemother. 2011;66(2):381-6.
    http://dx.doi.org/10.1093/jac/dkq424
  3. Muto CA, Jernigan JA, Ostrowsky BE, Richet HM, Jarvis WR, Boyce JM, et al. SHEA guideline for preventing nosocomial transmission of multidrug-resistant strains of Staphylococcus aureus and enterococcus. Infect Control Hosp Epidemiol. 2003;24(5):362-86.
    http://dx.doi.org/10.1086/502213
  4. Loveday HP, Pellowe CM, Jones SR, Pratt RJ. A systematic review of the evidence for interventions for the prevention and control of meticillin-resistant Staphylococcus aureus (1996-2004): report to the Joint MRSA Working Party (Subgroup A). J Hosp Infect. 2006;63 Suppl 1:S45-70.
    http://dx.doi.org/10.1016/j.jhin.2006.01.002
  5. Kalenic S, Cookson BD, Gallagher R, Popp W, Asensio-Vegas A, Assadian O, et al. Comparison of recommendations in national/regional Guidelines for prevention and control of MRSA. Int J Infect Control. 2010;6(2). doi: 10.3396/ijic.V6i2.016.10.
    http://dx.doi.org/10.3396/ijic.V6i2.016.10
  6. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006-12.
    http://dx.doi.org/10.1016/j.jclinepi.2009.06.005
  7. Aldeyab MA, Kearney MP, Hughes CM, Scott MG, Tunney MM, Gilpin DF, et al. Can the use of a rapid polymerase chain screening method decrease the incidence of nosocomial meticillin-resistant Staphylococcus aureus? J Hosp Infect. 2009;71(1):22-8.
    http://dx.doi.org/10.1016/j.jhin.2008.10.011
  8. Awad SS, Palacio CH, Subramanian A, Byers PA, Abraham P, Lewis DA, et al. Implementation of a methicillin-resistant Staphylococcus aureus (MRSA) prevention bundle results in decreased MRSA surgical site infections. Am J Surg. 2009;198(5):607-10.
    http://dx.doi.org/10.1016/j.amjsurg.2009.07.010
  9. Camus C, Bellissant E, Legras A, Renault A, Gacouin A, Lavoue S, et al. Randomized comparison of 2 protocols to prevent acquisition of methicillin-resistant Staphylococcus aureus: results of a 2-center study involving 500 patients. Infect Control Hosp Epidemiol. 2011;32(11):1064-72.
    http://dx.doi.org/10.1086/662180
  10. Chaberny IF, Schwab F, Ziesing S, Suerbaum S, Gastmeier P. Impact of routine surgical ward and intensive care unit admission surveillance cultures on hospital-wide nosocomial methicillin-resistant Staphylococcus aureus infections in a university hospital: an interrupted time-series analysis. J Antimicrob Chemother. 2008;62(6):1422-9.
    http://dx.doi.org/10.1093/jac/dkn373
  11. Chowers MY, Paitan Y, Gottesman BS, Gerber B, Ben-Nissan Y, Shitrit P. Hospital-wide methicillin-resistant Staphylococcus aureus control program: A 5-year follow-up. Infect Control Hosp Epidemiol. 2009;30(8):778-81.
    http://dx.doi.org/10.1086/599019
  12. Clancy M, Graepler A, Wilson M, Douglas I, Johnson J, Price CS. Active screening in high-risk units is an effective and cost-avoidant method to reduce the rate of methicillin-resistant Staphylococcus aureus infection in the hospital. Infect Control Hosp Epidemiol. 2006;27(10):1009-17.
    http://dx.doi.org/10.1086/507915
  13. Conterno LO, Shymanski J, Ramotar K, Toye B, van Walraven C, Coyle D, et al. Real-time polymerase chain reaction detection of methicillin-resistant Staphylococcus aureus: impact on nosocomial transmission and costs. Infect Control Hosp Epidemiol. 2007;28(10):1134-41.
    http://dx.doi.org/10.1086/520099
  14. Cunningham R, Jenks P, Northwood J, Wallis M, Ferguson S, Hunt S. Effect on MRSA transmission of rapid PCR testing of patients admitted to critical care. J Hosp Infect. 2007;65(1):24-8.
    http://dx.doi.org/10.1016/j.jhin.2006.09.019
  15. Ellingson K, Muder RR, Jain R, Kleinbaum D, Feng PJ, Cunningham C, et al. Sustained reduction in the clinical incidence of methicillin-resistant Staphylococcus aureus colonization or infection associated with a multifaceted infection control intervention. Infect Control Hosp Epidemiol. 2011;32(1):1-8.
    http://dx.doi.org/10.1086/657665
  16. Harbarth S, Masuet-Aumatell C, Schrenzel J, Francois P, Akakpo C, Renzi G, et al. Evaluation of rapid screening and pre-emptive contact isolation for detecting and controlling methicillin-resistant Staphylococcus aureus in critical care: an interventional cohort study. Crit Care. 2006;10(1):R25.
    http://dx.doi.org/10.1186/cc3982
  17. Harbarth S, Fankhauser C, Schrenzel J, Christenson J, Gervaz P, Bandiera-Clerc C, et al. Universal screening for methicillin-resistant Staphylococcus aureus at hospital admission and nosocomial infection in surgical patients. JAMA. 2008;299(10):1149-57.
    http://dx.doi.org/10.1001/jama.299.10.1149
  18. Hardy K, Price C, Szczepura A, Gossain S, Davies R, Stallard N, et al. Reduction in the rate of methicillin-resistant Staphylococcus aureus acquisition in surgical wards by rapid screening for colonization: a prospective, cross-over study. Clin Microbiol Infect. 2010;16(4):333-9.
    http://dx.doi.org/10.1111/j.1469-0691.2009.02899.x
  19. Holzmann-Pazgal G, Monney C, Davis K, Wanger A, Strobel N, Zhong F. Active surveillance culturing impacts methicillin-resistant Staphylococcus aureus acquisition in a pediatric intensive care unit. Pediatr Crit Care Med. 2011;12(4):e171-5.
    http://dx.doi.org/10.1097/PCC.0b013e3181f39222
  20. Huskins WC, Huckabee CM, O'Grady NP, Murray P, Kopetskie H, Zimmer L, et al. Intervention to reduce transmission of resistant bacteria in intensive care. N Engl J Med. 2011;364(15):1407-18.
    http://dx.doi.org/10.1056/NEJMoa1000373
  21. Huang SS, Yokoe DS, Hinrichsen VL, Spurchise LS, Datta R, Miroshnik I, et al. Impact of routine intensive care unit surveillance cultures and resultant barrier precautions on hospital-wide methicillin-resistant Staphylococcus aureus bacteremia. Clin Infect Dis. 2006;43(8):971-8.
    http://dx.doi.org/10.1086/507636
  22. Kurup A, Chlebicka N, Tan KY, Chen EX, Oon L, Ling TA, et al. Active surveillance testing and decontamination strategies in intensive care units to reduce methicillin-resistant Staphylococcus aureus infections. Am J Infect Control. 2010;38(5):361-7.
    http://dx.doi.org/10.1016/j.ajic.2009.09.018
  23. Jeyaratnam D, Whitty CJ, Phillips K, Liu D, Orezzi C, Ajoku U, et al. Impact of rapid screening tests on acquisition of meticillin resistant Staphylococcus aureus: cluster randomised crossover trial. BMJ. 2008;336(7650):927-30.
    http://dx.doi.org/10.1136/bmj.39525.579063.BE
  24. Jog S, Cunningham R, Cooper S, Wallis M, Marchbank A, Vasco-Knight P, et al. Impact of preoperative screening for meticillin-resistant Staphylococcus aureus by real-time polymerase chain reaction in patients undergoing cardiac surgery. J Hosp Infect. 2008;69(2):124-30.
    http://dx.doi.org/10.1016/j.jhin.2008.02.008
  25. Leonhardt KK, Yakusheva O, Phelan D, Reeths A, Hosterman T, Bonin D, et al. Clinical effectiveness and cost benefit of universal versus targeted methicillin-resistant Staphylococcus aureus screening upon admission in hospitals. Infect Control Hosp Epidemiol. 2011;32(8):797-803.
    http://dx.doi.org/10.1086/660875
  26. Martinez-Capolino C, Reyes K, Johnson L, Sullivan J, Samuel L, Digiovine B, et al. Impact of active surveillance on meticillin-resistant Staphylococcus aureus transmission and hospital resource utilisation. J Hosp Infect. 2010;74(3):232-7.
    http://dx.doi.org/10.1016/j.jhin.2009.10.018
  27. Reilly JS, Stewart S, Christie P, Allardice GM, Stari T, Matheson A, et al. Universal screening for meticillin-resistant Staphylococcus aureus in acute care: risk factors and outcome from a multicentre study. J Hosp Infect. 2012;80(1):31-5.
    http://dx.doi.org/10.1016/j.jhin.2011.09.008
  28. Pan A, Carnevale G, Catenazzi P, Colombini P, Crema L, Dolcetti L, et al. Trends in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections: effect of the MRSA "search and isolate" strategy in a hospital in Italy with hyperendemic MRSA. Infect Control Hosp Epidemiol. 2005;26(2):127-33.
    http://dx.doi.org/10.1086/502515
  29. Robicsek A, Beaumont JL, Paule SM, Hacek DM, Thomson RB, Jr., Kaul KL, et al. Universal surveillance for methicillin-resistant Staphylococcus aureus in 3 affiliated hospitals. Ann Intern Med. 2008;148(6):409-18.
    http://dx.doi.org/10.7326/0003-4819-148-6-200803180-00003
  30. Rodriguez-Bano J, Garcia L, Ramirez E, Lupion C, Muniain MA, Velasco C, et al. Long-term control of endemic hospital-wide methicillin-resistant Staphylococcus aureus (MRSA): the impact of targeted active surveillance for MRSA in patients and healthcare workers. Infect Control Hosp Epidemiol. 2010;31(8):786-95.
    http://dx.doi.org/10.1086/654003
  31. Shitrit P, Gottesman BS, Katzir M, Kilman A, Ben-Nissan Y, Chowers M. Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) decreases the incidence of MRSA bacteremia. Infect Control Hosp Epidemiol. 2006;27(10):1004-8.
    http://dx.doi.org/10.1086/507914
  32. Thompson DS, Workman R, Strutt M. Decline in the rates of meticillin-resistant Staphylococcus aureus acquisition and bacteraemia in a general intensive care unit between 1996 and 2008. J Hosp Infect. 2009;71(4):314-9.
    http://dx.doi.org/10.1016/j.jhin.2008.12.010
  33. Wang JT, Lauderdale TL, Lee WS, Huang JH, Wang TH, Chang SC. Impact of active surveillance and contact isolation on transmission of methicillin-resistant Staphylococcus aureus in intensive care units in an area with high prevalence. J Formos Med Assoc. 2010;109(4):258-68.
    http://dx.doi.org/10.1016/S0929-6646(10)60051-4
  34. Warren DK, Guth RM, Coopersmith CM, Merz LR, Zack JE, Fraser VJ. Impact of a methicillin-resistant Staphylococcus aureus active surveillance program on contact precaution utilization in a surgical intensive care unit. Crit Care Med. 2007;35(2):430-4.
    http://dx.doi.org/10.1097/01.CCM.0000253813.98431.28
  35. West TE, Guerry C, Hiott M, Morrow N, Ward K, Salgado CD. Effect of targeted surveillance for control of methicillin-resistant Staphylococcus aureus in a community hospital system. Infect Control Hosp Epidemiol. 2006;27(3):233-8.
    http://dx.doi.org/10.1086/500372
  36. Wernitz MH, Swidsinski S, Weist K, Sohr D, Witte W, Franke KP, et al. Effectiveness of a hospital-wide selective screening programme for methicillin-resistant Staphylococcus aureus (MRSA) carriers at hospital admission to prevent hospital-acquired MRSA infections. Clin Microbiol Infect. 2005;11(6):457-65.
    http://dx.doi.org/10.1111/j.1469-0691.2005.01152.x
  37. Malde DJ, Abidia A, McCollum C, Welch M. The success of routine MRSA screening in vascular surgery: A nine year review. Int Angiol. 2006;25(2):204-8.
  38. Lawes T, Edwards B, Lopez-Lozano JM, Gould I. Trends in Staphylococcus aureus bacteraemia and impacts of infection control practices including universal MRSA admission screening in a hospital in Scotland, 2006-2010: retrospective cohort study and time-series intervention analysis. BMJ Open. 2012;2(3):pii: e000797.
  39. Parvez N, Jinadatha C, Fader R, Huber TW, Robertson A, Kjar D, et al. Universal MRSA nasal surveillance: Characterization of outcomes at a tertiary care center and implications for infection control. South Med J. 2010;103(11):1084-91.
    http://dx.doi.org/10.1097/SMJ.0b013e3181f69235
  40. Kelly JC, O'Briain DE, Walls R, Lee SI, O'Rourke A, Mc Cabe JP. The role of pre-operative assessment and ringfencing of services in the control of methicillin resistant Staphylococcus aureus infection in orthopaedic patients. Surgeon. 2012;10(2):75-9.
    http://dx.doi.org/10.1016/j.surge.2011.01.008
  41. Kjonegaard R, Fields W, Peddecord KM. Universal rapid screening for methicillin-resistant Staphylococcus aureus in the intensive care units in a large community hospital. Am J Infect Control. 2013;41(1):45-50.
    http://dx.doi.org/10.1016/j.ajic.2012.01.038
  42. Eveillard M, Lancien E, Barnaud G, Hidri N, Gaba S, Benlolo JA, et al. Impact of screening for MRSA carriers at hospital admission on risk-adjusted indicators according to the imported MRSA colonization pressure. J Hosp Infect. 2005;59(3):254-8.
    http://dx.doi.org/10.1016/j.jhin.2004.09.028
  43. Lucet JC, Paoletti X, Lolom I, Paugam-Burtz C, Trouillet JL, Timsit JF, et al. Successful long-term program for controlling methicillin-resistant Staphylococcus aureus in intensive care units. Intensive Care Med. 2005;31(8):1051-7.
    http://dx.doi.org/10.1007/s00134-005-2679-0
  44. Troche G, Joly LM, Guibert M, Zazzo JF. Detection and treatment of antibiotic-resistant bacterial carriage in a surgical intensive care unit: a 6-year prospective survey. Infect Control Hosp Epidemiol. 2005;26(2):161-5.
    http://dx.doi.org/10.1086/502521
  45. Tomic V, Svetina Sorli P, Trinkaus D, Sorli J, Widmer AF, Trampuz A. Comprehensive strategy to prevent nosocomial spread of methicillin-resistant Staphylococcus aureus in a highly endemic setting. Arch Intern Med. 2004;164(18):2038-43.
    http://dx.doi.org/10.1001/archinte.164.18.2038
  46. Souweine B, Traore O, Aublet-Cuvelier B, Bret L, Sirot J, Laveran H, et al. Role of infection control measures in limiting morbidity associated with multi-resistant organisms in critically ill patients. J Hosp Infect. 2000;45(2):107-16.
    http://dx.doi.org/10.1053/jhin.2000.0734
  47. Gould IM, MacKenzie FM, MacLennan G, Pacitti D, Watson EJ, Noble DW. Topical antimicrobials in combination with admission screening and barrier precautions to control endemic methicillin-resistant Staphylococcus aureus in an Intensive Care Unit. Int J Antimicrob Agents. 2007;29(5):536-43.
    http://dx.doi.org/10.1016/j.ijantimicag.2006.12.019
  48. Bode LG, Kluytmans JA, Wertheim HF, Bogaers D, Vandenbroucke-Grauls CM, Roosendaal R, et al. Preventing surgical-site infections in nasal carriers of Staphylococcus aureus. N Engl J Med. 2010;362(1):9-17.
    http://dx.doi.org/10.1056/NEJMoa0808939
  49. Sankar B, Hopgood P, Bell KM. The role of MRSA screening in joint-replacement surgery. Int Orthop. 2005;29(3):160-3.
    http://dx.doi.org/10.1007/s00264-005-0649-3
  50. Sandri AM, Dalarosa MG, Ruschel de Alcantara L, da Silva Elias L, Zavascki AP. Reduction in incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infection in an intensive care unit: role of treatment with mupirocin ointment and chlorhexidine baths for nasal carriers of MRSA. Infect Control Hosp Epidemiol. 2006;27(2):185-7.
    http://dx.doi.org/10.1086/500625
  51. Boelaert JR, De Smedt RA, De Baere YA, Godard CA, Matthys EG, Schurgers ML, et al. The influence of calcium mupirocin nasal ointment on the incidence of Staphylococcus aureus infections in haemodialysis patients. Nephrol Dial Transplant. 1989;4(4):278-81.
  52. Camus C, Bellissant E, Sebille V, Perrotin D, Garo B, Legras A, et al. Prevention of acquired infections in intubated patients with the combination of two decontamination regimens. Crit Care Med. 2005;33(2):307-14.
    http://dx.doi.org/10.1097/01.CCM.0000152224.01949.01
  53. Cimochowski GE, Harostock MD, Brown R, Bernardi M, Alonzo N, Coyle K. Intranasal mupirocin reduces sternal wound infection after open heart surgery in diabetics and nondiabetics. Ann Thorac Surg. 2001;71(5):1572-8; discussion 8-9.
    http://dx.doi.org/10.1016/S0003-4975(01)02519-X
  54. Cordova KB, Grenier N, Chang KH, Dufresne R, Jr. Preoperative methicillin-resistant Staphylococcus aureus screening in Mohs surgery appears to decrease postoperative infections. Dermatol Surg. 2010;36(10):1537-40.
    http://dx.doi.org/10.1111/j.1524-4725.2010.01678.x
  55. Keshtgar MR, Khalili A, Coen PG, Carder C, Macrae B, Jeanes A, et al. Impact of rapid molecular screening for meticillin-resistant Staphylococcus aureus in surgical wards. Br J Surg. 2008;95(3):381-6.
    http://dx.doi.org/10.1002/bjs.6013
  56. Dupeyron C, Campillo B, Bordes M, Faubert E, Richardet JP, Mangeney N. A clinical trial of mupirocin in the eradication of methicillin-resistant Staphylococcus aureus nasal carriage in a digestive disease unit. J Hosp Infect. 2002;52(4):281-7.
    http://dx.doi.org/10.1053/jhin.2002.1287
  57. Dupeyron C, Campillo B, Richardet JP, Soussy CJ. Long-term efficacy of mupirocin in the prevention of infections with meticillin-resistant Staphylococcus aureus in a gastroenterology unit. J Hosp Infect. 2006;63(4):385-92.
    http://dx.doi.org/10.1016/j.jhin.2006.03.019
  58. Pofahl WE, Goettler CE, Ramsey KM, Cochran MK, Nobles DL, Rotondo MF. Active surveillance screening of MRSA and eradication of the carrier state decreases surgical-site infections caused by MRSA. J Am Coll Surg. 2009;208(5):981-8.
    http://dx.doi.org/10.1016/j.jamcollsurg.2008.12.025
  59. Fraser S, Brady RR, Graham C, Paterson-Brown S, Gibb AP. Methicillin-resistant Staphylococcus aureus in surgical patients: identification of high-risk populations for the development of targeted screening programmes. Ann R Coll Surg Engl. 2010;92(4):311-5.
    http://dx.doi.org/10.1308/003588410X12628812459698
  60. Gernaat-van der Sluis AJ, Hoogenboom-Verdegaal AM, Edixhoven PJ, Spies-van Rooijen NH. Prophylactic mupirocin could reduce orthopedic wound infections. 1,044 patients treated with mupirocin compared with 1,260 historical controls. Acta Orthop Scand. 1998;69(4):412-4.
    http://dx.doi.org/10.3109/17453679808999058
  61. Hadley S, Immerman I, Hutzler L, Slover J, Bosco J. Staphylococcus aureus Decolonization Protocol Decreases Surgical Site Infections for Total Joint Replacement. Arthritis. 2010;2010:924518. doi: 10.1155/2010/924518.
    http://dx.doi.org/10.1155/2010/924518
  62. Harbarth S, Dharan S, Liassine N, Herrault P, Auckenthaler R, Pittet D. Randomized, placebo-controlled, double-blind trial to evaluate the efficacy of mupirocin for eradicating carriage of methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 1999;43(6):1412-6.
  63. Kalmeijer MD, Coertjens H, van Nieuwland-Bollen PM, Bogaers-Hofman D, de Baere GA, Stuurman A, et al. Surgical site infections in orthopedic surgery: the effect of mupirocin nasal ointment in a double-blind, randomized, placebo-controlled study. Clin Infect Dis. 2002;35(4):353-8.
    http://dx.doi.org/10.1086/341025
  64. Kim DH, Spencer M, Davidson SM, Li L, Shaw JD, Gulczynski D, et al. Institutional prescreening for detection and eradication of methicillin-resistant Staphylococcus aureus in patients undergoing elective orthopaedic surgery. J Bone Joint Surg Am. 2010;92(9):1820-6.
    http://dx.doi.org/10.2106/JBJS.I.01050
  65. Kluytmans JA, Mouton JW, VandenBergh MF, Manders MJ, Maat AP, Wagenvoort JH, et al. Reduction of surgical-site infections in cardiothoracic surgery by elimination of nasal carriage of Staphylococcus aureus. Infect Control Hosp Epidemiol. 1996;17(12):780-5.
    http://dx.doi.org/10.1086/647236
    http://dx.doi.org/10.2307/30141170
  66. Konvalinka A, Errett L, Fong IW. Impact of treating Staphylococcus aureus nasal carriers on wound infections in cardiac surgery. J Hosp Infect. 2006;64(2):162-8.
    http://dx.doi.org/10.1016/j.jhin.2006.06.010
  67. Lipke VL, Hyott AS. Reducing surgical site infections by bundling multiple risk reduction strategies and active surveillance. Aorn J. 2010;92(3):288-96.
    http://dx.doi.org/10.1016/j.aorn.2010.01.016
  68. Milstone AM, Budd A, Shepard JW, Ross T, Aucott S, Carroll KC, et al. Role of decolonization in a comprehensive strategy to reduce methicillin-resistant Staphylococcus aureus infections in the neonatal intensive care unit: an observational cohort study. Infect Control Hosp Epidemiol. 2010;31(5):558-60.
    http://dx.doi.org/10.1086/652449
  69. Mody L, Kauffman CA, McNeil SA, Galecki AT, Bradley SF. Mupirocin-based decolonization of Staphylococcus aureus carriers in residents of 2 long-term care facilities: a randomized, double-blind, placebo-controlled trial. Clin Infect Dis. 2003;37(11):1467-74.
    http://dx.doi.org/10.1086/379325
  70. Muller A, Talon D, Potier A, Belle E, Cappelier G, Bertrand X. Use of intranasal mupirocin to prevent methicillin-resistant Staphylococcus aureus infection in intensive care units. Crit Care. 2005;9(3):R246-50.
    http://dx.doi.org/10.1186/cc3512
  71. Nicholson MR, Huesman LA. Controlling the usage of intranasal mupirocin does impact the rate of Staphylococcus aureus deep sternal wound infections in cardiac surgery patients. Am J Infect Control. 2006;34(1):44-8.
    http://dx.doi.org/10.1016/j.ajic.2005.07.004
  72. The Mupirocin Study Group. Nasal mupirocin prevents Staphylococcus aureus exit-site infection during peritoneal dialysis. Mupirocin Study Group. J Am Soc Nephrol. 1996;7(11):2403-8.
  73. Perl TM, Cullen JJ, Wenzel RP, Zimmerman MB, Pfaller MA, Sheppard D, et al. Intranasal mupirocin to prevent postoperative Staphylococcus aureus infections. N Engl J Med. 2002;346(24):1871-7.
    http://dx.doi.org/10.1056/NEJMoa003069
  74. Robicsek A, Beaumont JL, Thomson RB, Jr., Govindarajan G, Peterson LR. Topical therapy for methicillin-resistant Staphylococcus aureus colonization: impact on infection risk. Infect Control Hosp Epidemiol. 2009;30(7):623-32.
    http://dx.doi.org/10.1086/597550
  75. Suzuki Y, Kamigaki T, Fujino Y, Tominaga M, Ku Y, Kuroda Y. Randomized clinical trial of preoperative intranasal mupirocin to reduce surgical-site infection after digestive surgery. Br J Surg. 2003;90(9):1072-5.
    http://dx.doi.org/10.1002/bjs.4269
  76. Thomas S, Cantrill S, Waghorn DJ, McIntyre A. The role of screening and antibiotic prophylaxis in the prevention of percutaneous gastrostomy site infection caused by methicillin-resistant Staphylococcus aureus. Aliment Pharmacol Ther. 2007;25(5):593-7.
    http://dx.doi.org/10.1111/j.1365-2036.2006.03242.x
  77. Walsh EE, Greene L, Kirshner R. Sustained reduction in methicillin-resistant Staphylococcus aureus wound infections after cardiothoracic surgery. Arch Intern Med. 2011;171(1):68-73.
  78. Wertheim HF, Vos MC, Ott A, van Belkum A, Voss A, Kluytmans JA, et al. Risk and outcome of nosocomial Staphylococcus aureus bacteraemia in nasal carriers versus non-carriers. Lancet. 2004;364(9435):703-5.
    http://dx.doi.org/10.1016/S0140-6736(04)16897-9
  79. Wilcox MH, Hall J, Pike H, Templeton PA, Fawley WN, Parnell P, et al. Use of perioperative mupirocin to prevent methicillin-resistant Staphylococcus aureus (MRSA) orthopaedic surgical site infections. J Hosp Infect. 2003;54(3):196-201.
    http://dx.doi.org/10.1016/S0195-6701(03)00147-6
  80. Huang YC, Lien RI, Su LH, Chou YH, Lin TY. Successful control of methicillin-resistant Staphylococcus aureus in endemic neonatal intensive care units--a 7-year campaign. PLoS One. 2011;6(8):e23001.
    http://dx.doi.org/10.1371/journal.pone.0023001
  81. Ridenour G, Lampen R, Federspiel J, Kritchevsky S, Wong E, Climo M. Selective use of intranasal mupirocin and chlorhexidine bathing and the incidence of methicillin-resistant Staphylococcus aureus colonization and infection among intensive care unit patients. Infect Control Hosp Epidemiol. 2007;28(10):1155-61.
    http://dx.doi.org/10.1086/520102
  82. Yano M, Doki Y, Inoue M, Tsujinaka T, Shiozaki H, Monden M. Preoperative intranasal mupirocin ointment significantly reduces postoperative infection with Staphylococcus aureus in patients undergoing upper gastrointestinal surgery. Surg Today. 2000;30(1):16-21. http://dx.doi.org/10.1007/PL00010040
  83. Cepeda JA, Whitehouse T, Cooper B, Hails J, Jones K, Kwaku F, et al. Isolation of patients in single rooms or cohorts to reduce spread of MRSA in intensive-care units: prospective two-centre study. Lancet. 2005;365(9456):295-304.
    http://dx.doi.org/10.1016/S0140-6736(05)70193-8
    http://dx.doi.org/10.1016/S0140-6736(05)17783-6
  84. Bracco D, Dubois MJ, Bouali R, Eggimann P. Single rooms may help to prevent nosocomial bloodstream infection and cross-transmission of methicillin-resistant Staphylococcus aureus in intensive care units. Intensive Care Med. 2007;33(5):836-40.
    http://dx.doi.org/10.1007/s00134-007-0559-5
  85. Cheng VC, Tai JW, Chan WM, Lau EH, Chan JF, To KK, et al. Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant Staphylococcus aureus in intensive care unit. BMC Infect Dis. 2010;10:263.
    http://dx.doi.org/10.1186/1471-2334-10-263
  86. Curran ET, Hamilton K, Monaghan A, McGinlay M, Thakker B. Use of a temporary cohort ward as part of an intervention to reduce the incidence of meticillin-resistant Staphylococcus aureus in a vascular surgery ward. J Hosp Infect. 2006;63(4):374-9.
    http://dx.doi.org/10.1016/j.jhin.2006.02.017
  87. Fazal BA, Telzak EE, Blum S, Turett GS, Petersen-Fitzpatrick FE, Lorian V. Trends in the prevalence of methicillin-resistant Staphylococcus aureus associated with discontinuation of an isolation policy. Infect Control Hosp Epidemiol. 1996;17(6):372-4.
    http://dx.doi.org/10.2307/30141139
    http://dx.doi.org/10.1086/647322
  88. Gregory ML, Eichenwald EC, Puopolo KM. Seven-year experience with a surveillance program to reduce methicillin-resistant Staphylococcus aureus colonization in a neonatal intensive care unit. Pediatrics. 2009;123(5):e790-6.
    http://dx.doi.org/10.1542/peds.2008-1526
  89. Lecornet E, Robert J, Jacqueminet S, Van Georges H, Jeanne S, Bouilloud F, et al. Preemptive isolation to prevent methicillin-resistant Staphylococcus aureus cross-transmission in diabetic foot. Diabetes Care. 2007;30(9):2341-2.
    http://dx.doi.org/10.2337/dc07-0743
  90. Grayson ML, Russo PL, Cruickshank M, Bear JL, Gee CA, Hughes CF, et al. Outcomes from the first 2 years of the Australian National Hand Hygiene Initiative. Med J Aust. 2011;195(10):615-9.
    http://dx.doi.org/10.5694/mja11.10747
  91. Stone SP, Fuller C, Savage J, Cookson B, Hayward A, Cooper B, et al. Evaluation of the national Cleanyourhands campaign to reduce Staphylococcus aureus bacteraemia and Clostridium difficile infection in hospitals in England and Wales by improved hand hygiene: four year, prospective, ecological, interrupted time series study. BMJ. 2012;344:e3005.
    http://dx.doi.org/10.1136/bmj.e3005
  92. Lee AS, Huttner B, Harbarth S. Control of methicillin-resistant Staphylococcus aureus. Infect Dis Clin North Am. 2011;25(1):155-79.
    http://dx.doi.org/10.1016/j.idc.2010.11.002
  93. Haustein T, Gastmeier P, Holmes A, Lucet JC, Shannon RP, Pittet D, et al. Use of benchmarking and public reporting for infection control in four high-income countries. Lancet Infect Dis. 2011;11(6):471-81.
    http://dx.doi.org/10.1016/S1473-3099(10)70315-7
  94. Wyllie DH, Walker AS, Miller R, Moore C, Williamson SR, Schlackow I, et al. Decline of meticillin-resistant Staphylococcus aureus in Oxfordshire hospitals is strain-specific and preceded infection-control intensification. BMJ Open. 2011;1(1):e000160.
    http://dx.doi.org/10.1136/bmjopen-2011-000160
  95. Gurieva T, Bootsma MC, Bonten MJ. Successful Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections revisited. Clin Infect Dis. 2012;54(11):1618-20.
    http://dx.doi.org/10.1093/cid/cis272
  96. Vos MC, Behrendt MD, Melles DC, Mollema FP, de Groot W, Parlevliet G, et al. 5 years of experience implementing a methicillin-resistant Staphylococcus aureus search and destroy policy at the largest university medical center in the Netherlands. Infect Control Hosp Epidemiol. 2009;30(10):977-84.
    http://dx.doi.org/10.1086/605921
  97. Salgado CD, Farr BM. What proportion of hospital patients colonized with methicillin-resistant Staphylococcus aureus are identified by clinical microbiological cultures? Infect Control Hosp Epidemiol. 2006;27(2):116-21.
    http://dx.doi.org/10.1086/500624
  98. Tacconelli E, De Angelis G, de Waure C, Cataldo MA, La Torre G, Cauda R. Rapid screening tests for meticillin-resistant Staphylococcus aureus at hospital admission: systematic review and meta-analysis. Lancet Infect Dis. 2009;9(9):546-54.
    http://dx.doi.org/10.1016/S1473-3099(09)70150-1
  99. Jain R, Kralovic SM, Evans ME, Ambrose M, Simbartl LA, Obrosky DS, et al. Veterans Affairs initiative to prevent methicillin-resistant Staphylococcus aureus infections. N Engl J Med. 2011;364(15):1419-30.
    http://dx.doi.org/10.1056/NEJMoa1007474
  100. Jarlier V, Trystram D, Brun-Buisson C, Fournier S, Carbonne A, Marty L, et al. Curbing methicillin-resistant Staphylococcus aureus in 38 French hospitals through a 15-year institutional control program. Arch Intern Med. 2010;170(6):552-9.
    http://dx.doi.org/10.1001/archinternmed.2010.32
  101. Bootsma MC, Diekmann O, Bonten MJ. Controlling methicillin-resistant Staphylococcus aureus: quantifying the effects of interventions and rapid diagnostic testing. Proc Natl Acad Sci U S A. 2006;103(14):5620-5.
    http://dx.doi.org/10.1073/pnas.0510077103
  102. Raboud J, Saskin R, Simor A, Loeb M, Green K, Low DE, et al. Modeling transmission of methicillin-resistant Staphylococcus aureus among patients admitted to a hospital. Infect Control Hosp Epidemiol. 2005;26(7):607-15.
    http://dx.doi.org/10.1086/502589
  103. Wassenberg MW, Kluytmans JA, Box AT, Bosboom RW, Buiting AG, van Elzakker EP, et al. Rapid screening of methicillin-resistant Staphylococcus aureus using PCR and chromogenic agar: a prospective study to evaluate costs and effects. Clin Microbiol Infect. 2010;16(12):1754-61.
    http://dx.doi.org/10.1111/j.1469-0691.2010.03210.x
  104. Murthy A, De Angelis G, Pittet D, Schrenzel J, Uckay I, Harbarth S. Cost-effectiveness of universal MRSA screening on admission to surgery. Clin Microbiol Infect. 2010;16(12):1747-53.
    http://dx.doi.org/10.1111/j.1469-0691.2010.03220.x
  105. Carroll KC. Rapid diagnostics for methicillin-resistant Staphylococcus aureus: current status. Mol Diagn Ther. 2008;12(1):15-24.
    http://dx.doi.org/10.1007/BF03256265
  106. Malhotra-Kumar S, Haccuria K, Michiels M, Ieven M, Poyart C, Hryniewicz W, et al. Current trends in rapid diagnostics for methicillin-resistant Staphylococcus aureus and glycopeptide-resistant enterococcus species. J Clin Microbiol. 2008;46(5):1577-87.
    http://dx.doi.org/10.1128/JCM.00326-08
  107. Nulens E, Descheemaeker P, Deurenberg RH, Stobberingh EE, Gordts B. Contribution of two molecular assays as compared to selective culture for MRSA screening in a low MRSA prevalence population. Infection. 2010;38(2):98-101.
    http://dx.doi.org/10.1007/s15010-009-9117-0
  108. Laurent C, Bogaerts P, Schoevaerdts D, Denis O, Deplano A, Swine C, et al. Evaluation of the Xpert MRSA assay for rapid detection of methicillin-resistant Staphylococcus aureus from nares swabs of geriatric hospitalized patients and failure to detect a specific SCCmec type IV variant. Eur J Clin Microbiol Infect Dis. 2010;29(8):995-1002.
    http://dx.doi.org/10.1007/s10096-010-0958-3
  109. Wong H, Louie L, Lo RY, Simor AE. Characterization of Staphylococcus aureus isolates with a partial or complete absence of staphylococcal cassette chromosome elements. J Clin Microbiol. 2010;48(10):3525-31.
    http://dx.doi.org/10.1128/JCM.00775-10
  110. Blanc DS, Basset P, Nahimana-Tessemo I, Jaton K, Greub G, Zanetti G. High proportion of wrongly identified methicillin-resistant Staphylococcus aureus carriers by use of a rapid commercial PCR assay due to presence of staphylococcal cassette chromosome element lacking the mecA gene. J Clin Microbiol. 2011;49(2):722-4.
    http://dx.doi.org/10.1128/JCM.01988-10
  111. McConeghy KW, Mikolich DJ, LaPlante KL. Agents for the decolonization of methicillin-resistant Staphylococcus aureus. Pharmacotherapy. 2009;29(3):263-80.
    http://dx.doi.org/10.1592/phco.29.3.263
  112. Ammerlaan HS, Kluytmans JA, Wertheim HF, Nouwen JL, Bonten MJ. Eradication of methicillin-resistant Staphylococcus aureus carriage: a systematic review. Clin Infect Dis. 2009;48(7):922-30.
    http://dx.doi.org/10.1086/597291
  113. Buehlmann M, Frei R, Fenner L, Dangel M, Fluckiger U, Widmer AF. Highly effective regimen for decolonization of methicillin-resistant Staphylococcus aureus carriers. Infect Control Hosp Epidemiol. 2008;29(6):510-6.
    http://dx.doi.org/10.1086/588201
  114. Lucet JC, Regnier B. Screening and decolonization: does methicillin-susceptible Staphylococcus aureus hold lessons for methicillin-resistant S. aureus? Clin Infect Dis. 2010;51(5):585-90.
    http://dx.doi.org/10.1086/655695
  115. Lee AS, Macedo-Vinas M, Francois P, Renzi G, Vernaz N, Schrenzel J, et al. Trends in mupirocin resistance in meticillin-resistant Staphylococcus aureus and mupirocin consumption at a tertiary care hospital. J Hosp Infect. 2011;77(4):360-2.
    http://dx.doi.org/10.1016/j.jhin.2010.11.002
  116. Lee AS, Macedo-Vinas M, Francois P, Renzi G, Schrenzel J, Vernaz N, et al. Impact of combined low-level mupirocin and genotypic chlorhexidine resistance on persistent methicillin-resistant Staphylococcus aureus carriage after decolonization therapy: a case-control study. Clin Infect Dis. 2011;52(12):1422-30.
    http://dx.doi.org/10.1093/cid/cir233
  117. Morgan DJ, Diekema DJ, Sepkowitz K, Perencevich EN. Adverse outcomes associated with Contact Precautions: a review of the literature. Am J Infect Control. 2009;37(2):85-93.
    http://dx.doi.org/10.1016/j.ajic.2008.04.257
  118. Buhlmann M, Bogli-Stuber K, Droz S, Muhlemann K. Rapid screening for carriage of methicillin-resistant Staphylococcus aureus by PCR and associated costs. J Clin Microbiol. 2008;46(7):2151-4.
    http://dx.doi.org/10.1128/JCM.01957-07
  119. Cooper BS, Medley GF, Stone SP, Kibbler CC, Cookson BD, Roberts JA, et al. Methicillin-resistant Staphylococcus aureus in hospitals and the community: stealth dynamics and control catastrophes. Proc Natl Acad Sci U S A. 2004;101(27):10223-8.
    http://dx.doi.org/10.1073/pnas.0401324101
  120. Harbarth S, Hawkey PM, Tenover F, Stefani S, Pantosti A, Struelens MJ. Update on screening and clinical diagnosis of meticillin-resistant Staphylococcus aureus (MRSA). Int J Antimicrob Agents. 2011;37(2):110-7.
    http://dx.doi.org/10.1016/j.ijantimicag.2010.10.022
  121. Welsh CA, Flanagan ME, Kiess C, Doebbeling BN. Implementing the MRSA bundle in ICUs: one citywide collaborative's key lessons learned. Infect Control Hosp Epidemiol. 2011;32(9):918-21.
    http://dx.doi.org/10.1086/661101
  122. Köck R, Becker K, Cookson B, van Gemert-Pijnen J, Harbarth S, Kluytmans J, et al. Methicillin-resistant Staphylococcus aureus (MRSA): burden of disease and control challenges in Europe. Euro Surveill. 2010;15(41):19688.
     


Back to Table of Contents
Previous Download (pdf)
Next

The publisher’s policy on data collection and use of cookies.

Disclaimer: The opinions expressed by authors contributing to Eurosurveillance do not necessarily reflect the opinions of the European Centre for Disease Prevention and Control (ECDC) or the editorial team or the institutions with which the authors are affiliated. Neither ECDC nor any person acting on behalf of ECDC is responsible for the use that might be made of the information in this journal. The information provided on the Eurosurveillance site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her physician. Our website does not host any form of commercial advertisement. Except where otherwise stated, all manuscripts published after 1 January 2016 will be published under the Creative Commons Attribution (CC BY) licence. You are free to share and adapt the material, but you must give appropriate credit, provide a link to the licence, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.

Eurosurveillance [ISSN 1560-7917] - ©2007-2016. All rights reserved.
 

This website is certified by Health On the Net Foundation. Click to verify. This site complies with the HONcode standard for trustworthy health information:
verify here.