Controlling meticillin-susceptible Staphylococcus aureus: not simply meticillin-resistant S. aureus revisited

Journal of Hospital Infection 84 (2013) 13e21 Available online at www.sciencedirect.com

Journal of Hospital Infection journal homepage: www.elsevierhealth.com/journals/jhin

Review

Controlling meticillin-susceptible Staphylococcus aureus: not simply meticillin-resistant S. aureus revisited D. Lepelletier a, b, J.-C. Lucet c, d, * a

Unite´ de Gestion du Risque Infectieux, Service de Bacte´riologie-Hygie`ne, CHU de Nantes, Nantes, France Universite´ de Nantes, EA 3826, Faculte´ de Me´decine, Nantes, France c Unite´ d’Hygie`ne et de Lutte contre l’Infection Nosocomiale, Hoˆpital Bichat-Claude Bernard, Assistance Publique-Hoˆpitaux de Paris, Paris, France d Univ Paris Diderot, Sorbonne Paris Cite´, France b

A R T I C L E

I N F O

Article history: Received 23 October 2012 Accepted 7 January 2013 Available online 21 March 2013 Keywords: Staphylococcus aureus Carrier state Cross infection Epidemiology Meticillin resistance Mupirocin Staphylococcal infections

S U M M A R Y

Despite a large body of work evaluating the ability of meticillin-resistant Staphylococcus aureus (MRSA) screening and decolonization to decrease the risk of MRSA infection and transmission, many uncertainties remain regarding the efficacy of this strategy in hospitals located in endemic areas. With meticillin-susceptible S. aureus (MSSA), the objective is simply to eradicate the organism in order to diminish the risk of infection. MSSA decolonization was recently found to be effective in high-risk clean surgery, where the intervention was cost-effective and cost-saving. The many unanswered issues include the role for rapid screening tests, the optimal decolonization regimen, the indication for decolonization in other situations at risk, the frequency of replacement of S. aureus infections with infections due to other micro-organisms, and the risk of emergence of mupirocin resistance. ª 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Introduction Meticillin-resistant Staphylococcus aureus (MRSA) was a global threat and a major challenge to infection control at the end of the last century.1 At the dawn of the 21st Century, MRSA rates are decreasing in several European countries, although hospital-acquired MRSA rates vary.2,3 This favourable trend is the result of various preventive strategies4 including improved compliance with hand hygiene,5 screening and * Corresponding author. Address: Unite ´ d’Hygie `ne et de Lutte contre l’Infection Nosocomiale, Ho ˆpital Bichat-Claude Bernard, 46 rue Henri Huchard, 75018 Paris, France. Tel.: þ33 (1) 40 25 61 94; fax: þ33 (1) 40 25 88 11. E-mail address: [email protected] (J.-C. Lucet).

decolonization,6,7 contact precautions,8 the setting of national goals and public reporting.9e11 Community-acquired MRSA rates are increasing in Europe at various speeds depending on the country, and are rising more slowly than in the USA.12 MRSA dominated the field of infection control over the last 30 years, whereas meticillin-susceptible S. aureus (MSSA) was only a secondary concern. MSSA, however, remains an important pathogen. MSSA and MRSA in combination are the second greatest cause of healthcare associated infections (HAIs), and the main cause of surgical site infections (SSIs). In addition, MSSA incidence rates are increasing in Europe.13 MSSA has a comparable impact in terms of mortality and morbidity to that of MRSA, although MRSA infection generates additional costs.14e16 MSSA and MRSA differ in many ways. The prevalence of MSSA at hospital admission is approximately 25%, which is similar to

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that in the general population. The prevalence of MRSA is approximately 5% in hospitals from countries with endemic MRSA.17,18 However, the proportion of MRSA among S. aureus strains responsible for HAIs is approximately 50%, indicating that MRSA carriers are at higher risk for infection than MSSA carriers,19 and/or that MRSA is more easily transmitted between patients in the hospital. Actually, both hypotheses are probably true. MSSA infection originates from the endogenous flora present at hospital admission in 75e80% of cases, compared with approximately 50% for MRSA. Additionally, antibiotics play a role in the epidemiology of S. aureus by increasing the proportion of MRSA and decreasing the proportion of MSSA.20 Strategies to control S. aureus HAI include an individual objective for MSSA (i.e. preventing the development of MSSA infection in MSSA carriers) and a dual objective for MRSA (i.e. preventing infection in carriers and limiting cross-transmission between patients). In view of these epidemiological differences, one may view MRSA and MSSA as two different pathogens. As MRSA and MSSA have different epidemiological features,14,19 and because reviews discussed MRSA screening and decolonization,1,15,21 this article will focus on MSSA screening and decolonization and its role for HAI prevention.

S. aureus carriage in the general population S. aureus is a commensal and pathogenic bacterium responsible for infections at various anatomical sites in humans.22,23 The anterior nares are the most common site of S. aureus carriage. Nasal carriage is permanent in approximately 20% (12e30%) of the population, intermittent in approximately 30% (16e70%) and absent in 50% (16e69%).22 Variations in carriage rates across studies are ascribable to differences in screening methods, patient populations, and interpretations of carriage status definitions.24,25 Individual carriage rates are high at birth then diminish around the second month, reaching a plateau in adolescence and decreasing late in life. Furthermore, since the 1930s, carriage rates have decreased in the general population from 35% to 20e25%, probably as a result of better individual hygiene, improvements in standards of living and smaller sibship sizes.23 Nasal and cutaneous S. aureus carriage rates correlate closely with each other. For instance, cutaneous carriage on the hands is 27% in the general population and 90% among permanent nasal S. aureus carriers.22 Cutaneous carriage is a result of nasal carriage, as shown by Reagan et al.26 Mupirocin was compared with a placebo in 78 healthcare workers with stable S. aureus carriage. Mupirocin treatment eradicated the nasal carriage in all the workers but one, and eradication was sustained after three months in 71% of cases. S. aureus carriage on the hands was present at baseline in one-third of participants, and was eliminated in 80% of cases after nasal decontamination but persisted in 81% of participants in the placebo group. Studies recently established the major impact of S. aureus carriage in the gastrointestinal tract and throat.27,28 In a literature review, gastrointestinal S. aureus carriage without nasal carriage was found in up to 30% of study patients.28 The throat was the only carriage site in 13e23% of all carriers.27,29 Whether or not extranasal carriage influences the efficacy of decolonization and the risk of S. aureus infection is unknown.

Factors associated with nasal S. aureus carriage The factors associated with nasal S. aureus carriage are incompletely understood. Nasal carriage is probably multifactorial. Permanent carriers are at increased risk for infection30,31 and often carry a single S. aureus strain, whereas intermittent carriers may have several strains. In one study, healthy volunteers with or without known permanent S. aureus carriage were inoculated with several S. aureus strains.24 The non-carriers promptly eliminated the inoculated bacteria, whereas the permanent carriers selected their own strain, indicating a major role for hostebacteria interactions in carriage. These findings are supported by the variability in carriage rates across populations. S. aureus carriage is more common among Caucasians, males, and patients with underlying diseases including diabetes and renal failure requiring chronic haemodialysis or peritoneal dialysis. Chronic skin disease and acquired immunodeficiency syndrome are also risk factors for carriage.32 The studies that identified these risk factors usually included small numbers of patients, and most did not involve multi-variate analyses to detect independent risk factors. In a vast population of surgical patients, factors associated with nasal carriage of S. aureus e MSSA in the overwhelming majority of cases e were obesity, male gender and cardiovascular disease; in contrast, the prevalence of nasal S. aureus carriage was lower in smokers, older patients and patients who had taken antibiotics in the past month. In addition, environmental exposures associated with nasal MSSA carriage were hospital admission, carriage in family members and participation in group activities (e.g. football or rafting). Finally, nasal S. aureus carriage was influenced by biological factors such as adhesion and the host immune response.22,33

From S. aureus nasal carriage to infection in different patient populations Most cases of hospital-acquired S. aureus infection occur in nasal carriers.34,35 The risk of infection is increased three- to 12-fold in S. aureus carriers at admission compared with noncarriers.36,37 Nasal S. aureus carriage at admission is associated with an increased risk of healthcare-associated bloodstream infections, dialysis-associated infections and SSIs. In surgical patients, several studies performed before the era of prophylactic antibiotic therapy showed an association between nasal S. aureus carriage and SSIs. As early as 1959, Williams et al. reported S. aureus SSI rates of 2.1% in patients without nasal carriage and 6.8% in patients with nasal carriage.38 In half the patients with SSIs, similar organisms were recovered from the nasal swabs and surgical site.38 At the same time, other studies confirmed this association and indicated that the nasal and surgical site organisms were identical in 92% of cases.39 In several studies performed in general surgery,40 cardiac surgery41,42 or orthopaedic surgery,43 the risk of S. aureus SSI was increased two- to 10-fold in nasal carriers compared with non-carriers.36,44 Molecular studies indicated similarity between the nasal and SSI S. aureus strains in over 80% of cases.40,42 In some studies, however, over 50% of patients with S. aureus infection had no S. aureus carriage detected at admission to surgical40 or medical wards.44 Furthermore,

D. Lepelletier, J.-C. Lucet / Journal of Hospital Infection 84 (2013) 13e21 a small percentage of patients without carriage detected at admission had positive screening tests for nasal S. aureus carriage after surgery.40 These findings are consistent with the occurrence of S. aureus infections due to exogenous organisms, with cross-transmission occurring during or after surgery in non-carriers at admission. Another possibility is that admission screening may be insufficiently sensitive due to a low bacterial burden at sampled sites, incorrect sampling or carriage at unsampled sites.24,25,45 In dialysis patients, the prevalence of S. aureus carriage and the association between carriage and venous catheter-related infections have been studied for many years.46 The prevalence of nasal S. aureus carriage in dialysis patients ranged across studies from 32% to 57%, and most carriage strains were MSSA.47e49 The prevalence of MRSA carriage varied from 7% to 12%. Finally, a recent study showed that most S. aureus catheter-related bloodstream infections were due to MSSA.50

Microbiological methods and anatomical sites for screening for S. aureus carriage Two points were highlighted recently. First, carriage has been documented outside the nasal cavity, in the gastrointestinal tract and throat. Whether these carriage sites represent a reservoir for subsequent infection remains to be demonstrated. Indeed, recent interventional studies showed that nasal and cutaneous decolonization was effective in preventing SSI in cardiothoracic surgery patients. Whether digestive decontamination should be associated with nasal and skin decolonization before hip or knee prosthesis deserves to be tested. Second, cultures using agar plates differ in their sensitivity and response time.51 Chromogenic media with antibiotics help to identify MRSA more rapidly, with a turnaround time of 24 h (negative result) to 48e72 h (positive result).52 Rapid polymerase chain reaction (PCR) screening was introduced recently, with some techniques providing results within 1 h. These PCR tests are both sensitive and specific.53 These rapid techniques theoretically allow the initiation of decolonization in carriers within a few hours of hospital admission. However, when PCR tests were used in clinical practice, the time from screening to results was found to be approximately 24 h.18,54 In addition, a positive result for MRSA or S. aureus often results in no specific intervention. For example, only 43% of patients known to carry MRSA before surgery received adequate surgical prophylaxis in one study.18 In another study, 23% of MRSA carriers did not receive the prescribed decolonization regimen.55

Impact of nasal MSSA decolonization on S. aureus carriage The introduction of mupirocin in the late 1980s rekindled interest in nasal decontamination of carriers. Mupirocin is the topical agent most often assessed for the eradication of both MSSA and MRSA. Topical mupirocin calcium formulated as an ointment or cream (local application in the anterior nares, bid or tid for five days) is used alone or combined with other topical or systemic antimicrobial agents. A systematic review of six randomized clinical trials found no difference in MRSA eradication across interventions in four

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studies. The studies were heterogeneous in terms of the patient population, decolonization agents, protocols and endpoints.56 Many studies of MRSA decolonization used a beforeeafter design which has intrinsic limitations.55,57e59 These studies usually showed good efficacy in achieving decolonization. Other studies showed that MRSA decolonization was difficult,60 with eradication requiring systemic antibiotics, for example, in 65% of the patients in one study.61 Other studies indicate that, to be effective, application of the topical agent must be performed under direct supervision in elderly or bedridden patients.62 Insufficient supervision may lead to transient or failed decolonization despite an appropriately prescribed protocol.18,55 In addition, MRSA carriers share a number of characteristics that are obstacles to eradication, such as the presence of invasive devices, carriage at non-nasal sites (throat, skin lesions and other sites59), exposure to antibiotics,63 dependency for the activities of daily living, and low-level mupirocin resistance.29 Furthermore, although short-term eradication may be successful, long-term eradication is difficult to achieve.55,64,65 Decolonization of carriers is easier to achieve for MSSA than for MRSA. Decolonization was successful in over 90% of healthy volunteers and persisted several months later.66 Several reviews of studies in S. aureus carriers and non-carriers have been published.65,67e69 The few studies evaluating the efficacy of mupirocin ointment in eradicating MSSA carriage were undertaken in patients with recurrent staphylococcal skin and soft tissue infections.36 One study assessed various therapeutic and preventive methods in 80 patients with recurrent staphylococcal furunculosis. The most effective treatment was oral antibiotics for 10e14 days. Fusidic acid ointment was used to prevent relapses. Patients and healthy family members who carried the same strain as the patient applied the ointment to the nares twice daily every fourth week for 4e15 months. The effect was prolonged in 80% of cases.70 Another study described a successful strategy for terminating a community outbreak in a village in Germany.71 Nasal carriers, individuals with current furuncles or a history of relapsing furuncles, and their family members underwent stringent decolonization using mupirocin nasal ointment and disinfecting wash solution. The intervention was consistently successful in achieving decolonization, which was sustained in 78% of the individuals after seven and 20 weeks. Few studies are available in the hospital setting. In one large study, nasal S. aureus carriage was eliminated in 83% of patients who received mupirocin compared with 27% of patients given a placebo; carriage elimination rates were 81.3% with three to five doses of mupirocin and 93.3% with six doses or more.40 In another study, S. aureus carriage was eliminated in 82% of patients with mupirocin and in 29% of patients with the placebo.43 Finally, a third study showed elimination of nasal carriage in 81.5% of patients treated with mupirocin and 46.5% of those given the placebo.72 In these three studies, postoperative screening was either performed shortly after decolonization or at an undetermined date after surgery. Whether this single nasal negative screening represents true eradication or transient S. aureus suppression remains uncertain, but may be of minor importance given that the risk of wound contamination mainly occurs during the peri-operative period. Whether an antiseptic soap or solution should be used for skin and throat decolonization remains to be determined. In

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the light of: (i) probable efficacy in MRSA carriers,73 (ii) frequent carriage at non-nasal sites and (iii) the potential risk of failed decolonization and emergence of mupirocin resistance, it may be reasonable to combine nasal, skin and throat decolonization in MSSA carriers.74 There are a limited number of topical agents other than nasal mupirocin and body wash with chlorhexidine that can be used for S. aureus decolonization. Several agents for body wash or nasal S. aureus decolonization have been studied in small studies with different study designs and variable efficacy. They include chlorhexidine gluconate,75 polyhexanide,76 octenidine dihydrochloride77 and tea tree oil.78 A recent systematic review of 23 clinical trials evaluated different oral and topically applied antibiotics or products in either MSSA or MRSA carriers.79 This review showed that short-term nasal application of mupirocin is the most effective treatment for eradicating MRSA or MSSA carriage, with a reported effectiveness of mupirocin higher among healthy carriers than among patients.

Impact of decolonization on MSSA hospitalacquired infections In a randomized, double-blind, placebo-controlled trial of MSSA carriage in non-surgical inpatients, routine culture at admission followed by mupirocin application in S. aureus nasal carriers to prevent MSSA HAIs was not effective.80 This negative result may be ascribable to the study population (i.e. all patients instead of S. aureus carriers alone) and to the variable risk of infection in the patients who were admitted for a variety of conditions and interventions. Two systematic reviews have been published. The first reviewed the benefits of mupirocin treatment in patients undergoing haemodialysis or peritoneal dialysis.81 Although this was not stated in the report, most patients were MSSA carriers. Of the nine studies, only two were randomized controlled trials. The reduction in the risk of S. aureus infection was at least 62%, whatever the endpoint. The more recent systematic review focused on mupirocin decolonization in S. aureus carriers82 in nine randomized controlled trials published between 1989 and 2006, most of which included MSSA carriers. Decolonization significantly decreased the S. aureus infection rate (pooled odds ratio 0.55). This analysis included surgical patients, non-surgical patients and dialysis patients. Subgroup analyses revealed significant effects in surgical patients and dialysis patients. When SSI was used as the primary outcome in surgical patients, no statistically significant effect was found. Of note, infections caused by micro-organisms other than S. aureus were significantly increased in the mupirocin group (relative risk 1.38). This risk increase was mainly ascribable to a single study in peritoneal dialysis patients.83 Conceivably, infections with other micro-organisms may replace the S. aureus infections, especially when mupirocin decolonization is used for long periods, such as occurs in dialysis patients. More research in this field is required. In surgical patients, studies usually assessed mupirocin decolonization.34,41,62,74,84,85 Most studies were quasiexperimental and suggested that decolonization was effective in decreasing S. aureus SSI rates. However, there was no significant effect in two randomized placebo-controlled studies: in a large single-centre study in 3864 general surgery patients, S. aureus SSI rates were not significantly lower in the

intervention group (3.7%) compared with the placebo group (5.9%);40 the other study was performed in orthopaedic surgery patients and also found no significant difference, although the proportion of SSIs due to endogenous S. aureus was lower in the mupirocin group (0.3% vs 1.7%).43 Several reasons may account for these negative results. First, both studies included all patients, with or without S. aureus carriage. Decolonization with mupirocin is obviously only effective in S. aureus carriers, and the effect of the intervention may not be visible in the overall population. In a subgroup analysis, decolonization decreased the S. aureus SSI rate in S. aureus carriers.40 Second, nasal carriers only received nasal decolonization, without skin or throat decolonization.28,86 Finally, not all S. aureus carriers received the full five-day nasal decontamination protocol. Recently, a randomized placebo-controlled multi-centre study in surgical patients demonstrated the efficacy of a decolonization strategy involving both nasal mupirocin and skin and throat decolonization with chlorhexidine.74 All patients admitted for surgery, mainly heart surgery, were screened using a rapid PCR method. Decolonization was only started in S. aureus carriers. In the intervention group, there was a significant 58% reduction in S. aureus infections.74 In heart surgery patients, the reduction was 55% for superficial SSIs and 79% for deep SSIs. Decolonization significantly decreased the mean length of hospital stay by nearly two days. These data establish the beneficial effects of rapid PCR screening followed by decontamination of carriers in patients undergoing clean surgery, chiefly heart surgery. In this study, nearly all the S. aureus strains were MSSA. Decontamination was often started one or two days before surgery and was continued for five days in all. This study differs from previous randomized controlled trials in several ways. First, nasal S. aureus carriage was detected in real-time by PCR at hospital admission. This rapid screening method allows targeted decontamination within hours after admission, before patient exposure to healthcare procedures that carry a risk of S. aureus infection. Another important factor for risk reduction is the concomitant decontamination of extranasal sites (skin and oropharynx), which may produce a larger decrease in infections caused by endogenous S. aureus.22,73,86,87 The potential beneficial effects of S. aureus screening and nasal decontamination have been investigated extensively in other types of clean surgery, most notably orthopaedic surgery.88 To date, however, no incontrovertible proof of efficacy has been obtained. Mupirocin decolonization was successful in historical cohorts but has not been proven useful in randomized controlled trials.25,40,43,89,90 In dialysis patients, decolonization reduces subsequent infectious complications (peritoneal dialysis catheter exit site infections and peritonitis).65,91e93 A recent Cochrane Database analysis of 10 trials (786 patients) evaluated the effect of prophylactic topical antimicrobials, topical antiseptics, and medicated and non-medicated dressings on infection rates among haemodialysis patients with central venous catheters.94 Topical application of mupirocin ointment to the catheter exit site appears to be effective in reducing the risk of catheter-related bacteraemia. Insufficient reporting of mupirocin resistance was noted and will need to be improved in the future. However, European and American guidelines do not advocate this practice specifically.95,96 Other interventions at risk for MSSA infection (e.g. placement of long-term central venous catheter of mechanical

D. Lepelletier, J.-C. Lucet / Journal of Hospital Infection 84 (2013) 13e21 ventilation) may benefit from nasal decolonization, but there is no evidence of the efficacy of decolonization in these indications to date.

Resistance to mupirocin Mupirocin is the most widely used agent for nasal decolonization. Its use can result in the emergence of mupirocinresistant S. aureus strains. Three categories of mupirocin susceptibility have been reported:97 full susceptibility, minimum inhibitory concentration (MIC) 4 mg/mL; low-level resistance, MIC between 8 and 64 mg/mL; and high-level resistance, MIC 512 mg/mL. Strains with MICs between 128 and 256 mg/mL are uncommon. High-level resistance is related to the acquisition via a plasmid of the mupA gene for the enzyme isoleucyl-tRNA synthetase. Low-level resistance is probably related to a chromosomal mutation in the ileS gene. Studies have documented failure of nasal decontamination in patients carrying highly resistant MRSA strains.98 In contrast, the prevalence of strains with low levels of resistance is often too low to allow reliable assessment of decontamination failure. In a prospective study, the eradication rate for highly resistant MRSA strains was only 27% after three days of mupirocin treatment, compared with 78.5% for susceptible strains and 80% for strains with low levels of resistance.99 After one week, however, the patient groups with high-level and low-level resistance had the same low eradication rate of 25%, compared with 91% in patients with susceptible strains. A recent study confirmed that low-level resistance was among the factors associated with failed MRSA decontamination.29 Mupirocin resistance occurs chiefly in the event of widespread mupirocin use to treat MRSA skin infections,100,101 or nasal decontamination of MRSA carriers conducted with no predefined targeted strategy.102e105 Peri-operative mupirocin treatment to prevent S. aureus SSIs was not associated with an increase in resistant strains over a four-year period, and only six strains (0.6%) were resistant.40 Similarly, mupirocin use for four years for peri-operative prophylaxis in orthopaedic and vascular surgery patients with positive screening tests was not associated with an increase in low-level resistance, which remained stable at 7%. No highly resistant strains were identified.106 Finally, multi-centre surveillance data showed resistance to mupirocin in 5.4% of MRSA strains and 1.7% of MSSA strains.107 Mupirocin resistance is thus more common among MRSA strains than MSSA strains. The reason is probably the greater frequency of cross-transmission of MRSA than of MSSA, the shorter hospital stays in patients with MSSA compared with MRSA, and the higher decontamination failure rate for MRSA compared with MSSA. These studies suggest that targeted mupirocin use for nasal decontamination in surgical patients with positive screening tests may not increase mupirocin resistance rates significantly, at least in the short and medium terms.

Economic impact of screening and decontamination Cost/benefit studies of screening and isolation strategies are both numerous and heterogeneous. Most of them have focused on MRSA. A recent literature review highlighted the limitations of existing studies, which varied in terms of the

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interventions, methods used to compute the cost of an S. aureus infection, and methods for estimating the decline in infection rate associated with an intervention.108 Several studies have addressed the cost-efficacy and costsaving potential of MSSA decolonization using the SSI rate as the endpoint. Three studies in orthopaedic surgery concluded that the programme would be cost-effective in situations where decolonization decreased the S. aureus SSI rate by at least 20e30%.109e111 This conclusion held true for most scenarios, including those characterized by relatively low S. aureus SSI rates of approximately 1%.110,111 According to a recent study in clean surgery, based on realistic costs and expected efficacy, rapid screening and decolonization would be cost-effective and would save life-years in all scenarios.112 The best scenario was universal decolonization without screening, which was more effective than screening and decolonization of S. aureus carriers alone.

Questions to be answered In addition to the issue of the extent of decolonization before high-risk procedures, many questions remain to be answered regarding MSSA screening and decolonization. e Available data suggest that a complete decolonization regimen, including skin and throat decolonization, may be preferable to nasal decolonization alone, and that decolonization started one or two days before the surgical procedure is effective, at least for transient suppression. However, many practical questions remain: What is the usefulness of screening at non-nasal sites? What is the added value of skin and throat decolonization in addition to nasal mupirocin alone? What is the minimal duration of mupirocin treatment before surgery to ensure decolonization and to prevent S. aureus infections? e The efficacy of decolonization depends largely on the exhaustiveness of screening and on compliance with the decolonization regimen. The role for rapid screening and attentive supervision of decolonization in improving decolonization efficacy remains to be determined. e What is the risk of replacement of S. aureus infections by infections due to other micro-organisms after decolonization? e Universal decolonization regardless of carriage status is cost-saving and obviates the need for obtaining screening results before initiating targeted decolonization, thus making decolonization much simpler. Does the risk of mupirocin resistance in MSSA vary with the extent of the decolonized population? Unquestionably, S. aureus screening and decolonization are useful adjuncts to the set of preventive measures recommended for high-risk patients. MRSA received greater attention than MSSA in recent years. Several important issues will have to be addressed to determine the optimal extent and methods of screening and decolonization.

Conclusions Colonization with MRSA or MSSA is an established risk factor for S. aureus infection. Most studies have assessed the

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effectiveness of MRSA screening and decolonization in decreasing the HAI rate, using various criteria for success. The impact on mupirocin resistance has also been evaluated. The prevalence of MSSA at hospital admission is approximately five-fold higher than that of MRSA, but the risk of infection is higher in MRSA carriers.19,113 No risk factors for MSSA carriage have been identified, and all patients must be screened. The goal of screening is to achieve decolonization before an intervention that carries a risk of S. aureus infection (e.g. dialysis or clean surgery). In S. aureus carriers at low risk for infection, the available data do not support screening and decolonization. The strong evidence in favour of decolonization before heart surgery can probably be extrapolated to all types of thoracic surgery. Whether screening and decolonization should be used in other types of surgery depends on the frequency and severity of S. aureus infections. Studies are needed to assess the efficacy and cost-effectiveness of decolonization in other types of clean surgery, especially hip or knee replacement. Patients undergoing chronic haemodialysis or peritoneal dialysis might benefit from decolonization, although repeated treatment courses are needed, the effects are modest, and mupirocin resistance can emerge. Conflict of interest statement None declared. Funding sources None declared.

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