title: pre-operative screening for methicillin-resistant ... · methicillin resistant...

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Disclaimer : The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources and a summary of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright : This report contains CADTH copyright material. It may be copied and used for non-commercial purposes, provided that attribution is given to CADTH. Links : This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners’ own terms and conditions. TITLE: Pre-Operative Screening for Methicillin-Resistant Staphylococcus aureus (MRSA) Infection: A Review of the Clinical-Effectiveness and Guidelines DATE: 9 July 2009 CONTEXT AND POLICY ISSUES: Methicillin resistant Staphylococcus aureus (MRSA) has become a widespread pathogen, with outbreaks observed in hospital and community settings throughout the world. 1-3 Prompt diagnosis is required to avert the further spread of this bacteria, which can often lead to invasive infections such as necrotizing fasciitis, bursitis, osteomyelitis, and bacteremia, with some cases resulting in death. 1 MRSA is endemic worldwide in hospitals. 3 The percentage of MRSA among S aureus isolates in US hospitals increased from 2.4% in 1975 to 29.0% in 1991, and in 2003, the percentage methicillin resistance among patients in intensive care units infected with S aureus was 53%. 1 While rates of MRSA are lower in Canada than in the US, outbreaks in Canada have been reported throughout the country and prevalence is increasing substantially. 4 Between 1995 and 2005, the rate of MRSA in Canadian hospitals increased from 0.46 to 5.90 per 1000 admissions. 3 In 2007, the estimated rate of MRSA infection in Canadian hospitals remained approximately the same (5.87 cases per 1000 admissions), and 4728 cases of MRSA infection were reported in 47 sentinel hospitals across the country. 5 The health care costs attributable to MRSA infection in Canada were estimated to be $82 million in 2004, and are expected to reach $129 million by 2010. 3 In an effort to avoid the costly health and economic burden of MRSA infection, some health care facilities have turned to screening patients before or at time of admission to hospital in an effort to control the prevalence and spread of MRSA on its wards and to their patients. The efficacy of this preventive measure, and the identification of which populations should be screened (global vs. targeted), have been subjects of some debate. 6 In patients being admitted for elective procedures, it is sometimes recommended that MRSA screening take place several days before surgery, with the intention of maximizing preventive practices such as decolonization, however whether or not this practice is evidence-based is unclear. 6

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Disclaimer: The Health Technology Inquiry Service (HTIS) is an information service for those involved in planning and providing health care in Canada. HTIS responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources and a summary of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. HTIS responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material. It may be copied and used for non-commercial purposes, provided that attribution is given to CADTH. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners’ own terms and conditions.

TITLE: Pre-Operative Screening for Methicillin-Resistant Staphylococcus aureus (MRSA) Infection: A Review of the Clinical-Effectiveness and Guidelines

DATE: 9 July 2009 CONTEXT AND POLICY ISSUES: Methicillin resistant Staphylococcus aureus (MRSA) has become a widespread pathogen, with outbreaks observed in hospital and community settings throughout the world.1-3 Prompt diagnosis is required to avert the further spread of this bacteria, which can often lead to invasive infections such as necrotizing fasciitis, bursitis, osteomyelitis, and bacteremia, with some cases resulting in death.1 MRSA is endemic worldwide in hospitals.3 The percentage of MRSA among S aureus isolates in US hospitals increased from 2.4% in 1975 to 29.0% in 1991, and in 2003, the percentage methicillin resistance among patients in intensive care units infected with S aureus was 53%.1 While rates of MRSA are lower in Canada than in the US, outbreaks in Canada have been reported throughout the country and prevalence is increasing substantially.4 Between 1995 and 2005, the rate of MRSA in Canadian hospitals increased from 0.46 to 5.90 per 1000 admissions.3 In 2007, the estimated rate of MRSA infection in Canadian hospitals remained approximately the same (5.87 cases per 1000 admissions), and 4728 cases of MRSA infection were reported in 47 sentinel hospitals across the country.5 The health care costs attributable to MRSA infection in Canada were estimated to be $82 million in 2004, and are expected to reach $129 million by 2010.3 In an effort to avoid the costly health and economic burden of MRSA infection, some health care facilities have turned to screening patients before or at time of admission to hospital in an effort to control the prevalence and spread of MRSA on its wards and to their patients. The efficacy of this preventive measure, and the identification of which populations should be screened (global vs. targeted), have been subjects of some debate.6 In patients being admitted for elective procedures, it is sometimes recommended that MRSA screening take place several days before surgery, with the intention of maximizing preventive practices such as decolonization, however whether or not this practice is evidence-based is unclear.6

The present review was conducted with the aim of informing decisions regarding MRSA screening in healthcare facilities, by specifically reviewing the recent evidence for the efficacy of hospital-based MRSA screening programs, by identifying which patient populations are recommended to be included in a screening program, and by summarizing recommendations for the timing of screening relative to surgical procedures. RESEARCH QUESTIONS: 1. What is the clinical-effectiveness of pre-operative methicillin-resistant staphylococcus

aureus screening? 2. What are the guidelines for the timing of pre-operative methicillin-resistant staphylococcus

aureus screening? 3. Is there evidence to guide the selection of patients who should be screened pre-

operatively for methicillin-resistant staphylococcus aureus? METHODS: A limited literature search was conducted on key health technology assessment resources, including PubMed, The Cochrane Library (Issue 2, 2009), University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, EuroScan, international HTA agencies, and a focused Internet search. The search was limited to English language articles published from 2004 to June 2009. No filters were applied to limit the retrieval by study type. The search was supplemented with hand-searching of selected references. Eighty-seven references were identified in the literature search, and 19 were identified from the grey literature. Two references were identified from the hand-search. From these 108 references, 35 reports were retrieved for further assessment. These reports included: health technology assessments, systematic reviews or meta-analyses, randomized and non-randomized control trials, observational studies, and practice guidelines. The retrieved full reports were again screened and their relevance to the research questions was confirmed. After final screening, a total of 19 reports were selected for this review. Among the observational studies retrieved for final screening, only those that compared screening for MRSA to no screening were included. Reasons for exclusion of reports in the final stage of study selection were: not a guideline, guideline not relevant to hospital setting, not a screening study, not a comparative study, comparison of two screening methods, reporting of findings inconsistent and deemed unreliable, and primarily a costing study. HTIS reports are organized so that the higher quality evidence is presented first. Therefore, health technology assessment reports and systematic reviews are presented first. These are followed by randomized and clinical controlled trials, observational studies, and evidence-based guidelines. SUMMARY OF FINDINGS: One health technology assessment,7 one systematic review,8 nine observational studies,9-17 and eight practice guidelines18-25 were identified. No randomized controlled trials were identified. Health Technology Assessments

Pre-operative screening for MRSA 2

The National Health Service in Scotland published a health technology assessment of the clinical-effectiveness and cost-effectiveness of screening for MRSA in acute in-patients hospital settings in 2007.7 Because UK guidelines provided contradictory recommendations of the MRSA screening process, as well as the targeted screening patient populations, this assessment by Ritchie et al. was commissioned to consider the different MRSA screening strategies and appropriate management of patients found to be colonized with MRSA. A systematic literature review was performed, with the primary intent of populating the accompanying economic model. To this end, nine literature searches with specific research objectives were conducted. The topics of the nine searches were: prevalence of MRSA, MRSA detection using clinical risk assessment, diagnostic accuracy of tests for MRSA, management of MRSA, staff screening, association of colonization to infection, and three searches related to decolonization. Multiple databases and sources were searched, and searches were conducted up to 2006. The economic model considered six screening strategies (Table 1): Table 1: Screening strategies studied in model in Ritchie et al.7 Strategy Details

1 No clinical risk assessment, no swab screening of any patient. 2 No clinical risk assessment, swab screening of high-risk and low-risk specialty unit

patients. 3 No clinical risk assessment, swab screening of only high-risk specialty unit patients. 4 Clinical risk assessment of high and low-risk specialty unit patients with subsequent

swab screening of all likely carriers 5 Clinical risk assessment of all low-risk specialty unit patients with subsequent swab

screening of all likely carriers, swab screening of all high-risk specialty unit patients. 6 Clinical risk assessment of high and low-risk specialty unit patients. Patients are then

placed in pre-emptive isolation based on result of clinical risk assessment. Regardless of clinical risk assessment result, all patients undergo swab screening. This strategy assesses the value of pre-emptive isolation.

The model assumed that all patients in high-risk specialty units who were identified as MRSA- colonized received decolonization treatment for nose, throat and skin carriage. The settings for this model were an 840-bed tertiary referral hospital, and a large general hospital comprised an average of 480 beds. The model findings demonstrated that the introduction any screening strategy would reduce the prevalence of MRSA within the hospital. Screening patients in both high and low-risk specialty groups achieved a much greater reduction in prevalence than screening only one group, and the magnitude of the prevalence reduction was strongly influenced by the accuracy of the screening method (i.e. clinical risk assessment or laboratory testing). The model predicted that the cumulative number of infections in the tertiary referral setting with no screening strategy increased from 329 (95%CI: 325-333) to 1,671 (95%CI:1,660-1,683) over a five year period. Over this same five-year period, the number of infections under screening strategy two ranged from 65 (95%CI:63-67) to 79 (95%CI:77-81), those for screening strategy three ranged from 93 (95%CI:91-95) to 157 (95%CI:153-160), and those for strategy five ranged from 68 (95%CI:66-70) to 86 (95%CI:83-88). For the least effective strategy (i.e. Strategy 3), at the end of the first year on average 236 MRSA infections would be avoided, and over 5 years, a total of 1,517 infections would be avoided. For the most effective strategy where all admitted patients would be screened (Strategy 2), 1,592 infections would be avoided over 5 years. Using Strategy 5 would result in on average 1,585 infections being avoided. The authors noted several limitations with the studies and the data included in this report; however they concluded that a policy that identifies MRSA-colonized individuals and subsequently manages them to prevent transmission will reduce MRSA prevalence in the

Pre-operative screening for MRSA 3

patient population, and that the associated morbidity and mortality of health care associated MRSA infections will also be reduced. Among their recommendations were the need for a primary inpatient study of the effectiveness of screening on MRSA infection, further study of staff MRSA transmission, systems to monitor and evaluate infection control strategies, high quality patient data on MRSA, and more sensitive care of patients in isolation for treatment of MRSA infection. Systematic Reviews McGingle et al.8 published a systematic review of the use of active surveillance cultures (ASCs) in adult intensive care units (ICUs) to reduce MRSA-related morbidity, mortality and costs in 2008. A literature search of several databases was conducted up to 2007. Studies were included in this review if they were in the English language, involved patients from medical or surgical ICUs, occurred in a non-outbreak setting, measured hospital acquired drug-resistant s. aureus, obtained at least weekly cultures of samples from nares of all ICU patients in the intervention group, had primary outcomes of MRSA transmission or infection or MRSA-related mortality, morbidity, or costs, and had any one of the following study designs: experimental, quasi-experimental, controlled observational, uncontrolled before-and-after studies, or ecological studies. A total of 2,558 citations were reviewed for inclusion, and 20 studies fulfilled the selection criteria. There were no randomized controlled trials. Sixteen observational studies (only two of which had a control group), and four economic reports were identified. All selected studies were assessed for quality and internal validity. None were determined to be of ‘good’ quality, seven were considered to be of ‘fair’ quality, and 13 were deemed to be of poor quality. Because of the inherent weakness of uncontrolled studies, the maximum rating this type of study could obtain was ‘fair’ and all before-and-after studies were of poor quality. An additional four economic reports were also selected and only two of the reports were true cost-benefit analyses with good internal validity and appropriate statistical analysis. The authors reported that 13 of the 16 observational studies, including the two controlled studies, had a decrease in the incidence of hospital-acquired MRSA infections in association with the use of ASCs, with the majority of these studies reporting a 40%-60% decrease in hospital-acquired MRSA incidence associated with ASCs in ICU settings. Of the three studies that reported negative findings, two reported no change in MRSA infection rates and the third specifically separated the surveillance cultures from other subsequent patient management (e.g. contact isolation) and did not report test results to staff. In this study, mean daily prevalence MRSA rates did not change and there was no cross-contamination of MRSA between patients in the ICU. The authors of that study concluded that had the ASC program been followed up with isolation precautions, ASCs would have appeared falsely successful and were not a useful infection control strategy. In their discussion, McGingle et al. note that in the United States, there is no standard definition of what constitutes an “active surveillance culture” and which patients should be screened for MRSA colonization is not clear. They recommend the screening of high-risk patients as possible options (e.g., readmissions, ICU admissions, transfers, patients with high-risk medical conditions, history of MRSA infection, or frequent medical facility contact). McGingle et al. also noted that the literature, including a Cochrane review of trials, does not support the use of topical or systemic medications for MRSA decolonization, however over one half of the studies in this systematic review used decolonization as part of their intervention program. The authors also reported that few of the reviewed studies reported levels of compliance with performing nasal swabs for active surveillance of MRSA. The authors had some concern over potential publication bias in this review, as studies of fair or poor quality with negative findings are less likely to be published. McGingle et al. conclude that the evidence from multiple observation-based studies suggests that the use of ASC reduces the incidence of

Pre-operative screening for MRSA 4

MRSA infection, but because of the overall poor quality of the evidence, definitive evidence-based recommendations can not be made. They suggest that while a randomized controlled trial would be helpful, it may not be feasible because of high cost, and that it may be best to make use of available evidence that demonstrates the usefulness of ASCs in reducing MRSA infection and MRSA-related costs, and further define the details of methods for effective ASC implementation (e.g., risk assessment, lower cost rapid method cultures or polymerase chain reaction [PCR], treatment for colonized patients). Observational Studies In 2009, Pofhal et al.9 published a study of the impact of best practices and active surveillance screening for MRSA on reduction of MRSA surgical site infections (SSIs). Patients undergoing operations under the Centers for Medicare and Medicaid Services Surgical Infection Prevention Project (SIPP) at Pitt County Memorial Hospital (PCMH) in North Carolina were screened for SSIs. Procedures for which patients underwent SSI surveillance included those for cardiac, vascular, orthopedic, colorectal, and gynecological surgery; however data for patients undergoing vascular and colorectal surgery were excluded due to data accuracy issues. Starting in 2001, PCMH began screening patients from groups at high risk for carriage of MRSA on admission. High-risk groups included transfers from nursing homes, home health care patients, dialysis patients, patients transferred from other acute care facilities with admissions of more than 4 days, and patients who were previously culture-positive for MRSA. On February 1st 2007, PCMH started screening all admissions for MRSA through duplicate nasal swabs of the anterior nares. Carriage of MRSA was detected using a rapid PCR-based assay. Beginning February 15th 2007, all patients scheduled for elective operations were screened for MRSA, and patients with positive screens were treated prior to surgery with 2% nasal mupirocin ointment twice daily for five days and with 4% chlohexidine gluconate bathing on days one, three, and five of the mupirocin treatments. Any changes in peri-operative antibiotics in MRSA-positive patients were at the discretion of the attending surgeon. The authors identified two groups for the purposes of the study analysis. Group one consisted of 8.469 SIPP patients undergoing procedures between January 1st 2004 and February 15th 2007. Group two included 5,094 SIPP patients that were operated on after February 15th 2007. Results of this study are provided in Table 2. Table 2: Results of study by Pofhal et al.9 Group 1 Group 2 SIPP procedures (n) Cardiac: Hysterectomy: Orthopedics: All patients:

3,307 1,810 1,979 8,469

2,055 1,198 1,436 5,094

Rate of nasal MRSA colonization All admitted patients: Surgical patients:

NA NA

7.2% 6.8%

MRSA SSIs (rate per 100 procedures) Cardiac§: Hysterectomy§: Orthopedics*: All patients:

0.24 0.11 0.30 0.23

0.20 0.09 0.00 0.09

MRSA: Methicillin Resistant Staphylococcus aureus; NA: not applicable; SSI: surgical site infection; SIPP: Surgical Infection Prevention Project; §: rate not reported explicitly and estimated from graph; *P=0.04 (chi-square test with Yate’s continuity correction, two-tailed)

Pre-operative screening for MRSA 5

MRSA SSIs developed in seven patients after universal screening was initiated (Group 2). Four of these patients had positive MRSA screens, and none had received pre-operative eradication of MRSA. The rate of MRSA SSI was lower in group two (all patient subgroups and total), however this difference was statistically significant only in the orthopedic subgroup (0.30 per 100 procedures versus 0.00 per 100 procedures, p=0.04). The authors note that their policy of high-risk screening may have positively impacted the observed baseline rates of MRSA SSIs, and that institution of SIPP guidelines may have affected MRSA SSI rates by optimizing antibiotics use throughout the course of the study. The authors concluded that surveillance for MRSA and eradication of the carrier state reduces the rate of MRSA SSI, and recommended further prospective studies at a range of health care institutions to evaluate the value of this approach to MRSA infection management. Richer et al.10 reported on the effectiveness of preoperative screening and the treatment of MRSA in otolaryngological surgical practice at a US hospital in 2009. This retrospective chart review examined the infection rates of 241 patients who were operated from August 1st 2005 to July 30th 2006 without prior screening, to 179 patients that were screened preoperatively between August 1st 2006 and June 30th 2007. Patients were screened using a nasal swab and carriage of MRSA was detected using a real-time PCR test. Patients who tested positive for MRSA were treated with 2% mupirocin calcium ointment to the anterior nares two times a day for 5 days, a 4% chlorhexadine wash or shower on days 1, 3, and 5 of treatment, and there were no changes in antimicrobial prophylaxis throughout the study. A post-surgical infection was defined as a positive wound culture from a surgical site within 30 days of surgery. Following chart review, 42 (17%) of patients in the pre-screening period and 36 (20%) of patients in the screening period were categorized as high risk for MRSA infection. There were two reported MRSA-related post-surgical infections in the pre-screening group. Among those patients identified in the screening period, 97 (54.2%) were screened for MRSA, 24 (13.4%) had colonized with bacteria in the anterior nares, two were MRSA positive, and none of the patients in this group developed post-surgical infections. The criteria for decision to screen in the second group were not specified in the report. The authors concluded that early results show the potential benefit of preoperative S aureus screening in MRSA infection rate reduction, but that larger studies in this area are needed. A study of the effect of an early MRSA detection strategy on hospital MRSA infection rates in surgical patients was reported by Harbarth et al.11 in 2008. This prospective interventional cohort study included 21,754 patients from the wards of eight surgical departments (abdominal surgery, orthopedics, urology, neurosurgery, cardiovascular surgery, thoracic surgery, plastic surgery, and solid organ transplantation) of a Swiss teaching hospital with endemic MRSA. All patients admitted to the surgical department for more than 24 hours were included. A crossover design was used to compare two MRSA control strategies: rapid screening on admission plus standard infection control measures, versus standard infection control measures alone. Each of the eight surgical specialties was assigned to either the intervention or control group and enrolled according to a study plan that involved four phases: a baseline surveillance period without MRSA screening on admission (July to September 2004); intervention period 1 (October 2004 to June 2005) which was a nine-month intervention period, followed by a 2-month washout period during which follow-up for MRSA infection was continued in all wards, followed by a cross-over period (September 2005) and intervention period 2 (September 2005 to May 2006) during which time the two groups of wards changed intervention. Rapid screening on admission involved the systematic sampling of the anterior nares and perineal region, as well as other sites where clinically indicated. A multiplex immunocapture-coupled quantitative polymerase chain reaction (qPCR) developed at the hospital centre was used for rapid diagnosis of MRSA carriage through detection of the mecA gene. Standard infection control measures were used

Pre-operative screening for MRSA 6

for all patients with MRSA in all wards and consisted of contact isolation of identified MRSA carriers, use of dedicated material (gown, gloves, and if indicated, mask), adjustment of perioperative antibiotic prophylaxis of MRSA carriers, computerized MRSA alert system, and topical decolonization (nasal mupirocin ointment and chlorhexidine body washing) of known MRSA carriers for 5 days. Patients who went to the operating room before the 5 day decolonization regimen completed treatment after surgery. The primary study outcome was the overall rate of nosocomial MRSA infection per 1,000 patient-days. Infections occurring more that 48 hours after admission and less than 72 hours after discharge were considered to be hospital-acquired. Secondary outcomes included the rate of surgical site infection due to MRSA (per 100 procedures, and occurring within 30 days of surgery), and the nosocomial MRSA acquisition rate, expressed as the number of new cases of MRSA detected by clinical culture more that 48 hours after admission in previously MRSA-free patients. Post-discharge surveillance for MRSA infection was conducted for up to 30 days after surgery (either inpatient or outpatient). The study had 70% power to detect a reduction in MRSA infection rate from 0.9% to 0.6% in the rapid detection group. Incidence rate ratios of nosocomial MRSA infection were calculated using Poisson regression. Only one MRSA infection was considered per patient per hospital stay. The number of patients with nosocomial MRSA infections in a given month was the dependent variable. Independent variables included intervention or control group status, the monthly number of admitted patients with previously known MRSA carriage, study month, monthly use of alcohol-based hand rubs, and antibiotic selection pressure exerted by antibiotics without activity against MRSA. The control and intervention periods were comparable with regards to several study characteristics. Both periods were for duration of 18 months. The number of admissions in the control and intervention periods was 10,910 and 10,844, respectively. The number of patient days in the control periods was 83,120, and in the intervention period they were 83,757. The number of surgical procedures in the control and intervention periods was 6,072 and 6,130, respectively. The consumption of antibiotics without MRSA activity was 33,805 defined daily doses (DDD) in the control periods, and 34,346 DDD in the intervention periods. There were 149 previously known MRSA carriers admitted in the control periods and 178 admitted in the intervention periods, relative risk is 1.2 (95% CI: 0.97-1.49) Of the 10,844 patients followed in the intervention group, 6,483 were followed in the first intervention period, and 4,165 were followed in the second intervention period. Of these 10,844 patients, 10,193 (94%) received rapid molecular screening. Six percent did not receive rapid screening due to one of several reasons, including the expected low risk of MRSA carriage based on a previously established risk index (n=491), constraint due to life-threatening conditions (n=16), refusal (n=5), or early discharge or death (n=139). Twenty-six MRSA-positive patients were detected at out-patient visits, and 489 were detected at hospital admission, for a total of 515 cases (5.1%). The median time from screening to notification of results was 22.5 hours (inter-quartile range: 12.2-28.2). Three-hundred and eighty-six detected MRSA carriers underwent surgery and of these, 120 patients were given notification of their MRSA result after surgery because of emergency surgery and time delays in result notification. One hundred and fifteen of the remaining 266 patients who were identified before surgery received perioperative antibiotic prophylaxis. There were no significant reductions in MRSA infection found in the intervention periods compared with the control periods. The number of patients with any type of nosocomial MRSA infection found in the control and intervention periods was 76 (0.7%) and 93 (0.9%), respectively. Total incidence in the two periods was 0.91 per 1000 patients days (control) and 1.11 per 1000 patient days (intervention), incidence rate ratio (IRR) = 1.2 (95%CI:0.9-1.7). A total of 88 MRSA infections were reported in the control periods, and 103 were reported in the intervention periods. It was noted that patients may have had multiple site infections. The rate of

Pre-operative screening for MRSA 7

SSIs due to MRSA was 0.99 per 100 surgical interventions in the control periods, and 1.14 per 100 surgical interventions in the intervention periods, IRR=1.2 (95%CI: 0.8-1.7). The number of patients with nosocomial MRSA acquisition in the control and intervention periods was 132 and 142, respectively. Finally, the incidence of nosocomial MRSA acquisition per 1000 patient days in the control and intervention periods was 1.59 and 1.69, respectively, IRR=1.1 (95%CI: 0.8-1.4). The authors suggested several possible reasons for the negative results of this study. First, overall infection rates were low for a centre with endemic MRSA prevalence, making the finding of a significant intervention effect less likely. Second, 53 of 93 infected patients (57%) were MRSA-free on admission and acquired MRSA infection during hospitalization. The authors stated that this demonstrates the limited value of screening on admission of patients that stay in hospital for an extended period of time, and note that postoperative transmission may play an important role in the cause of MRSA infection. Third, positive test results for 31% of patients were available only after surgery and 34% of patients with MRSA surgical site infection who could have benefited from MRSA prophylaxis did not receive this regimen. Fourth, more previously-known MRSA carriers were admitted during the intervention period, suggesting higher colonization pressure and limited availability of isolation rooms, however adjustment for this variable did not affect results. Among the study limitations identified by the authors were: non-randomized assignment to study interventions; the trial was not designed to detect true MRSA cross-transmission rates, and doing so would have presented a logistical and resource challenge because of the large sample size, however it is noted that systematic misclassification bias was unlikely; and conventional cultures to confirm positive results of molecular tests were not performed, leading to possible detection bias, though distortion of the primary outcome measure through false-positive screening results are unlikely. The authors concluded that the study did not show an added benefit for widespread rapid screening on admission compared with standard MRSA control alone in preventing nosocomial MRSA infections. The authors recommended that MRSA screening be targeted to surgical patients who undergo elective procedures with a high risk of MRSA infection, and that in such cases, earlier identification would allow sufficient time for optimal pre-operative decontamination and prophylaxis. The authors also recommended that surgical services and infection control teams should carefully assess their local MRSA epidemiology and patient profiles before introducing a universal screening program. In 2008, Jog et al.12 published a study on the impact of MRSA screening using a real-time PCR test in patients undergoing cardiac surgery. This study was conducted at a UK teaching hospital from October 2004 to September 2006, and compared the rate of surgical site MRSA infection in 1,462 patients in the 12 months before and after the institution of an MRSA screening program. The lack of pre-assessment clinic made determination of MRSA status prior to admission difficult and rapid PCR testing for MRSA was performed on patients admitted the day before surgery. The screening program involved the collection of a single nose swab in Stuart’s medium from each patient on admission. Nasal mupirocin 2% ointment 3 times per day and topical triclosan 2% was started immediately pending the test results. If the MRSA test result was negative, treatment was discontinued and the patient was given standard peri-operative antibiotic prophylaxis. It the test result was positive, the mupirocin and triclosan were continued for 5 days as well as peri-operative antibiotic prophylaxis. This latter regimen was given to any patients with previous MRSA colonization (regardless of screening results), to patients of unknown MRSA status, and to patients who had been on the ward for more than 96 hours since their last screen. Standard infection control policies were followed before and after the institution of the screening program, and these included ward audits and education, and daily cardiac ward rounds by a microbiologist. Throughout the course of the study, there were no changes in ward cleaning routines or products, or of line care of management of ventilators and endotrachial

Pre-operative screening for MRSA 8

tubes, and similar precautions were taken when MRSA was isolated from a pre-operative screen or a later culture. In the period during which screening was not conducted (October 2004 to September 2005), 697 patients underwent cardiac surgery, and eight (1.15%) developed an SSI attributable to MRSA. A total of 765 cardiac surgery patients were followed in the screening phase of the study (October 2005 to September 2006), and 681 (89%) were screened for MRSA using the real-time PCR assay. A total of 2 (0.26%) patients developed MRSA-related SSI s during this period, and the difference in the rates observed in the two time periods was statistically significant (p<0.05). None of the patients identified preoperatively as being MRSA carriers developed post-operative infections due to MRSA. It should be noted that duration or setting of follow-up for assessment of outcome was not specified in this report, although infections were identified up to 40 days post-surgery in some patients. In addition, it is unclear whether patients were followed prospectively for any or part of the duration of the study. The authors acknowledge that possible changes in MRSA epidemiology and management may influence infection rates, but that no such changes could be identified in this study. The authors concluded that PCR screening at the time of cardiac surgery is feasible in routine clinical practice and is associated with a significant reduction in subsequent MRSA SSIs. Robicsek et al.17 reported a study of the effect of two expanded surveillance interventions on MRSA infection in a three-hospital, 850-bed health organization with 40,000 annual admissions in 2008. Expanded surveillance was assessed using a before-and-after design with three distinct periods. During period one (August 2003 to July 2004), there was no active surveillance, and no decolonization was performed on patients found to be MRSA-positive based on clinical cultures, however, MRSA-positive patients were placed in contact isolation. In period two (August 2004 to July 2005), surveillance was introduced for all ICU admissions, and patients found to be MRSA-positive on nasal culture and real-time PCR test were isolated (decolonization was not a standard policy). Time to test results was 2.5 days. In period three (August 2005 to April 2007), surveillance was introduced for all hospital admissions, nasal surveillance was completed in an average of 0.67 days, and decolonization was recommended. Decolonization consisted of a 5-day regimen with mupirocin calcium 2% twice daily to the nares, and a chlorhexidine 4% wash or shower every two days. Patients who were discharged before decolonization therapy was completed were sent home with a prescription in order to complete the treatment. Adherence to decolonization therapy was not monitored however pharmacy data for decolonization treatments were available. The primary outcome of the study was the aggregate hospital-associated MRSA infection rate, defined as the sum of all MRSA bloodstream, respiratory, urinary tract, and surgical site infections occurring more than 48 hours after admission, and through 30 days after discharge. The secondary outcomes for this study were the rates of health-care associated MRSA and methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia, the rates of aggregate MRSA infections occurring up to 180 days after discharge, and adherence to MRSA surveillance. All outcomes were ascertained retrospectively using hospital administrative data. Analyses of the primary and secondary outcomes were performed using Poisson regression models. The days during which a patient that was colonized or infected with MRSA was appropriately placed in isolation was also measured. A total of 39,521, 40,392, and 73,427 patients were hospitalized in periods one, two, and three, respectively. During period two, 3,334 of 4,392 (75.9%) ICU admissions were tested for MRSA, and 277 (8.3%) were positive. In period three, 62,035 of 73,464 (84.4%) of admissions were tested for MRSA, and 3,926 (6.3%) were positive. Data on mupirocin use were available for 2,085 patients who tested positive for MRSA in period three, and at least four doses were administered in 1,288 (62%) cases. At least one chlorhexidine wash was administered in 1,044 of the 1,883 admissions (55%) for which data were available. The aggregate hospital-associated MRSA prevalence density per 10,000 patient days during periods one, two, and three was 8.9 (95%CI: 7.6 to 10.4), 7.4 (95%CI:6.1 to 9.0), and 3.9 (95%CI:3.2 to

Pre-operative screening for MRSA 9

4.7), respectively. Using a segmented Poisson regression model, the change in infection rate was -36.2% (95%CI:-65.4% to 9.8%) between periods one and two, -52.4% (95%CI: -78.3% to -9.3%) between periods two and three, and -69.6% (95%CI: -89.2% to -19.6%) between periods one and three. The rate of MRSA bacteremia statistically significantly decreased in period three, compared with period one (absolute reduction: 1.1 per 10,000 patient days [95%CI: -1.9 to -0.2]), however rates of MSSA did not change. While some reduction was seen in aggregate MRSA infection in the 30 days after discharge in each of the three study periods, this effect did not extend in the 31 to 180 days after discharge. Adherence to universal surveillance was initially 75% but increased to 90% by the end of period three. A total of 11,454 patient-days were spent in isolation during period three. It was estimated that patients whose MRSA would have detected by clinical culture alone (period one) would have spent 2,036 days in isolation (17.8% of those in period three). In period two, 3,814 isolation days (33.3% of those in period three) would have been observed. The authors noted several limitations with this study. First, the fact that MRSA disease rates declined during the universal surveillance period (period three) does not prove a causal association. Also, detection of some infections occurring post-discharge may have been missed if patients were treated outside the hospital system. Finally, the authors noted that they did not monitor adherence to decolonization therapy, and that the efficacy of decolonization is undetermined and requires further study. It is not stated explicitly that similar contact isolation was available to all patients in the three periods. Given the quicker turn-around time for test results in period three (compared with period two), and the inconclusive evidence regarding decolonization, it is difficult to say whether the declines in MRSA infection observed in the third period were due to obtaining test results and achieving patient isolation more quickly, whether they were due to decolonization practices, or if both these factors played a role. The authors concluded that the introduction of universal surveillance for MRSA was associated with a large reduction in MRSA disease during admission and 30 days post-discharge. A UK study of the impact of rapid PCR screening for MSRA in nine specialty wards of the University College London Hospitals was reported by Keshtgar et al.13 in 2007. Prior to 2006, routine screening for MRSA was not conducted at these centers. In 2006, all patients admitted for critical care or routine or emergency surgery, were screened for MRSA. Screening involved a nasal swab and a subsequent rapid PCR test. MRSA-positive patients were prescribed a suppression protocol, which was expected to start 5 days before surgery, or the operation might be delayed. The suppression protocol was started immediately in the more urgent cases. The suppression protocol consisted of nasal mupirocin (2%) 3 times per day and undiluted chlorhexidine gluconate (4%) as a body wash, as well as a shampoo on days one, three, and five. Clothing and bed linens were also changed daily. Since 2000, the hospital wound surveillance team had examined wounds for at least six months by a combination of observation, questioning of staff, examination of case notes, and telephone or postal contact with the patients. Patients were excluded from wound surveillance if they stayed if their hospital stay was less than two nights or if their procedure did not involve wounding. There were no changes in antibiotic prophylaxis procedures against MRSA between 2000 and 2006. Between January 16th and December 31st 2006, 20,477 screening samples were received, of which 18810 (92%) were processed. Reasons for discarding of samples included: samples from inappropriate sites; duplicate nares; and patients found to be MRSA-positive on previous screen. Eight-hundred and fifty MRSA-positive samples (4.5%) were found. Fifty-three patients developed MRSA bacteremia over the screening period, 41 of which were in the screened population and 12 of which were non-surgical cases. The annual mean number (and range) of cases in similar patient populations from 2000 to 2005 were 67 (53-87) and 29 (17-45), respectively. Incidence rates for MRSA infection and related wound infection are given in Table 3.

Pre-operative screening for MRSA 10

Table 3: Incidence rates for MRSA and wound infection rates in Keshtgar et al.13

MRSA cases

MRSA incidence, per 1000 patient days (n)

Year

Blood

Wound

Number of patients days

Bacteremia

Wound

2000-2005 86* 317* 1,469,399 0.39 (573) 1.44 (2110) 2005 86* 384* 186,867 0.39 (73) 1.74 (325) 2006 53 277 221,027 0.24 (53) 1.25 (277) MRSA: Methicillin Resistant Staphylococcus aureus; *:expected numbers based on 2000-2005 figures. The overall rate of MRSA bacteremia per 1000 patients days fell by 38.6% from 2005 to 2006 (p<0.001; two tailed Fisher’s exact test) and by 38.5% compared with the annual mean in 2000-2005 (p<0.001). The authors cautioned with regards to the interpretation of the results because four months before the start of the screening program (in 2005), most inpatients had been moved to a new building, and this coincided with an increased incidence of MRSA infection. The authors concluded that rapid MRSA screening of all surgical admissions resulted in a significant reduction in staphylococcal bacteremia during the screening period, although a causal link could not be established. Thomas et al.14 reported a case-control study that assessed the impact of screening and antibiotic prophylaxis on preventing MRSA infection in percutaneous endoscopic gastrostomy (PEG) in 2007. This study retrospectively ascertained new peristomal infections that occurred at Wycombe Hospital (UK) from January 2002 to September 2004, and compared them to prospectively detected infections occurring during a screening and prophylaxis program that began in October 2004, up to August 2006. In the retrospective phase of the study, clinical details were obtained for any patient where MRSA had been isolated from a PEG site up to one month following their procedure. During the screening phase of the study, patients were screened by swabs of the nose, throat, perineum, and any other broken skin area together with a urine sample if catheterized and were tested for MRSA with a culture method. Patients found to be MRSA positive were given treatment with mupirocin nasal ointment for every eight hours and daily skin decontamination with Aquasept (2% triclosan) washed for 5 days prior to the PEG insertion. When necessary, the procedure was delayed to allow for completion of the decontamination protocol. MRSA patients also received prophylactic teicoplanin 400 mg intravenously 30 minutes before the procedure. Patients who were MRSA-negative were given prophylactic co-amoxiclav 1.2-1.8 g intravenously 30 minutes prior to the procedure, or alternatively cefuroxime 1.5 g intravenously for penicillin-allergic patients. Patients were followed for a period of one month post-procedure (both in hospital and in the community) by the hospital’s infection control team. The rates of MRSA infections before the introduction of screening and prophylaxis were 12% in 2002, 20% in 2003, and 29% between January and September of 2004. The rate of MRSA infection during the screening period (October 2004 to August 2006) dropped to 2% The reduction in MRSA infection rate during the screening period, when compared with the previous overall infection rate, and with each of the two previous years (2003, and January to September 2004) was statistically significant (compared with overall rate: Chi-Square=5.16, p<0.025; to 2003, Chi-Square=4.35, p<0.05, and to 2004, Chi-Square=6.76, p<0.01).

The rates of overall MRSA colonization and infection at Wycombe Hospital between 2000 and 2004 had been reported are given in Table 4:

Pre-operative screening for MRSA 11

Table 4: MRSA isolates at Wycombe Hospital, 2000-200414

Year Number of new MRSA isolates 2000 277 2001 384 2002 374 2003 472 2004 503

MRSA: Methicillin Resistant Staphylococcus aureus The authors concluded that an active screening decontamination and antibiotic prophylaxis protocol identifies cases of MRSA colonization in patients undergoing PEG tube placement and can significantly reduce the risk of peristomal PEG site infections. In 2006, Clancy et al.15 published a study that looked at the effectiveness of active screening for MRSA in high-risk units in a 400-bed US hospital. The study included patients aged 18 years and older who were admitted to a ward or transferred to the medical and surgical ICUs of the hospital. The pre-intervention period was defined as January 1st 2002 to March 30th 2003. The screening period was defined as April 1st 2003 to June 30th 2004. During this period, patients were screened for MRSA by a swab of the anterior nares and were tested for MRSA colonization with a commercial latex agglutination kit (Remel). Swabs were then taken weekly during ICU stays, with the exception of patients who were absent during weekly screening or patients with a known history of MRSA colonization or infection. Patients with a positive nasal swab were considered to be colonized, and patients who had a positive clinical specimen (which was ordered to evaluate for infection) were considered to be infected. MRSA-positive patients (colonized or infected) in both study periods were placed in contact isolation. The primary outcome of the study was incidence of MRSA infection, and infection rates were calculated as both a total rate (clinical specimen positive from time of admission forward), and as nosocomial rates (first clinical specimen positive >72 hours after admission). Secondary outcomes included percent of ICU patients colonized or infected with MRSA on admission, the mean number of patients who developed nosocomial infections, and the difference in clonality of the pulse-field gel electrophoresis (PFGE) patterns between pre-intervention and post-intervention periods. Statistically significant reductions in the primary outcome were seen for all three hospital areas combined, and for the surgical ICU. Infection reductions in the medical ICU were not statistically significant. Community-acquired MRSA rates increased during the post-intervention period, and most of these patients were admitted to wards, which may explain the corresponding increased total rate in MRSA infection on wards in the post-intervention period. The results for the primary outcome are shown in Table 5: Table 5: Incidence of MRSA infection in Clancy et al.15 Medical unit Pre-intervention Post-intervention p-value All units Total rate (per 1,000 days) Nosocomial rate (per 1,000 days)

6.1 4.5

4.1 2.8

0.01

<0.01 Surgical ICU Total rate (per 1,000 days) Nosocomial rate (per 1,000 days)

9.4 9.1

4.9 4.7

<0.005 <0.002

Medical ICU Total rate (per 1,000 days) Nosocomial rate (per 1,000 days)

7.8 4.0

5.6 3.3

0.17 0.62

Wards

Pre-operative screening for MRSA 12

Medical unit Pre-intervention Post-intervention p-value Total rate (per 1000 days) Nosocomial rate (per 1000 days)

1.2 0.53

1.8 0.32

0.24 0.17

MRSA: Methicillin Resistant Staphylococcus aureus; ICU: intensive care unit With regards to the secondary outcomes, 70 of 1890 patients who had swab samples done on admission (3.7%) were colonized or infected with MRSA. This rate was higher in the medical ICU (4.5%) than in the surgical ICU (2.1%), p=0.01. The mean number of hospital days prior to nosocomial MRSA infection increased from 15 days during the pre-intervention period to 19 days in the post intervention period, however this difference was not statistically significant (p=0.15). Clinical isolates from the pre-intervention period (n=42) and post-intervention period (n=41) were compared and it was shown that the percentage of patients infected with the predominant clone of MRSA at this hospital (type A0) did not change during the 30 month study period. The authors note that they were not able to assess the impact of the opening of a new medical ICU and wards soon after the start of the post-intervention period. The authors also note that rates of MRSA infection decreased for the first time in years in the post-intervention period, despite several study limitations. They concluded that even in a setting of increasing community-associated MRSA, active MRSA screening as a part of a multi-faceted intervention targeted to high-risk units may be an effective strategy for achieving a sustained decrease in MRSA infections throughout the hospital. Sankar et al.16 (2005) prospectively compared rates of hospital-acquired MRSA infection in patients undergoing hip and knee replacement surgery, before and after institution of a program for compulsory MRSA swabbing at one UK hospital. Between October 16th 2000 and October 15th 2001, 395 patients were admitted to the elective orthopedic ward. On April 16th 2001, it became mandatory hospital policy that al patients admitted to the elective orthopedic ward be MRSA-negative. After this date, all patients underwent swabbing of the axilla, nose, groin, and any open wounds at an outpatient clinic, one week prior to admission (MRSA screening test used not reported). MRSA-positive patients were treated with mupirocin or povidone iodine or triclosan, and admission was delayed until three consecutive negative swabs were obtained. Outcomes included the incidence of overall and individual infective complications, and length of hospital stay. The authors reported significantly higher post-operative infection rates and MRSA infection rates, as well as longer length of stay among all patients in the first period. The results of this study are provided in Table 6. Table 6: Primary and secondary outcomes reported in Sankar et al.16 Group 1 Group 2 p-value Time period Oct 16th 2000 to

April 15th 2001 April 16th 2001 to October 15th 2001

-

Number of patients 164 231 - Post-operative complications, n(%) All§ Infections only

17 (10.4%) 14 (8.5%)

13 (5.6%) 8 (3.5%)

NR

P<0.05 MRSA Infections, n (%) SSIs LRTIs Total

1 (0.6%) 3 (1.8%) 4 (2.4%)

0 0 0

NR NR

P<0.05 Length of stay (mean days ± SD) All patients Infection complications excluded

10.4±4.2 9.6±2.7

9.5±2.6 9.3±2.3

P<0.05

NR

Pre-operative screening for MRSA 13

MRSA: Methicillin Resistant Staphylococcus aureus; SSI: surgical site infection; LRTI: lower respiratory tract infections; NR: not reported; SD: standard deviation; §: includes SSIs, LRTIs, urinary tract infections, hip dislocation, deep vain thrombosis, and pulmonary embolism; The authors concluded that the screening of elective orthopedic patients for MRSA decreases morbidity by reducing hospital-acquired infections and is highly cost-effective. Guidelines Of the eight guidelines reviewed for this report, three18-20 did not recommend pre-operative screening for MRSA and two of these guidelines19,20 indicated that the evidence for decolonization using mupirocin was inconclusive. One guideline18 recommended management of MRSA at patient admission and during the perioperative period, but did not specify if management involved clinical assessment and /or screening. All three of these guidelines originated in the United States. The remaining five guidelines in this review recommended screening for MRSA, and all five originated in the UK. The Chelsea and Westminster Hospital of the National Health Service (NHS) Foundation Trust published a policy for MRSA screening in 2009.21 The methods used to derive the recommendations were not provided in the document. The recommendations for the timing of screening were: preferably in pre-operative assessment or out-patient clinic at least one week before admission for elective procedures to allow for five days of decolonization; on admission for emergency surgical patients; and prior to surgery for any emergency patient who is scheduled for surgery but is already an inpatient. Populations recommended for screening included: all elective admissions (surgical and medical); admissions to ICU, neonatal units, and burn units; admissions from ICU; transfer from wards with suspected MRSA outbreaks; patients with previous admissions of ≥1 nights; patients with past MRSA infection; and transfers from residential care facilities. Screening during topical eradication and during treatment (and for 2 days after) with antibiotics was not recommended. The North Yorkshire Community Infection Prevention and Control Policies and Guidance for MRSA was published in 200922. Methods used to derive recommendations were not provided in the guidelines. The guideline stated that screening will take place for planned hospital admissions, and that for specific advice regarding screening, one should contact the admitting hospital. A five-day decolonization / eradication program was recommended. No further details regarding timing of screening or the screening of specific patient groups are provided. The UK Cystic Fibrosis (CF) Trust published guidelines for management and treatment of MRSA in CF patients in 2008.23 Each recommendation was assigned one of three grades of recommendation based on six levels of evidence as per the Agency of Health Care Policy Research (1992) methodology (Table 7). Table 7: Levels of evidence and grades of recommendation in CF Trust MRSA guidelines23 Grade of recommendation

Levels and types of evidence Type of recommendation

A Ia: evidence from meta-analysis of RCTs Ib: evidence from at least one RCT

Requires at least one RCT as part of the body of literature of overall good quality and consistency addressing the specific

Pre-operative screening for MRSA 14

Grade of recommendation

Levels and types of evidence Type of recommendation

recommendation B IIa: evidence from at least one well-

designed study without randomization IIb: Evidence from at least one other type of quasi-experimental study III: evidence from well-designed non-experimental descriptive studies

Requires availability of well conducted clinical studies but no randomized trials on the topic of recommendation

C IV: evidence from expert committee reports or opinions or clinical opinions of respected authorities

Requires evidence from expert committee reports or opinions and/or clinical experiences of respected authorities. Indicates absence of directly applicable studies of good quality.

RCT: randomized controlled trial The guidelines recommend screening of CF patients at respiratory sites for MRSA at each hospital visit, and at non-respiratory sites on or before admission to hospital for elective surgery, with a view to implementing a decolonization program. These recommendations were assigned a grade of C. The London Department of Health published best practices for MRSA screening in 2006.24 The methods used to derive the recommendations were not provided in the document. The guidelines stated that there is good evidence and/or strong consensus that screening should be applied to the following patient groups: preoperative surgical patients in certain surgical specialties, particularly orthopedics, cardiothoracic, and neurosurgery; emergency orthopedic or trauma admissions; ICU and high dependency unit (HDU) patients; renal patients; patients with previous MRSA-positive culture; all elective surgery patients; oncology/chemotherapy patients; patients admitted from high-risk settings such as nursing homes; and all emergency admissions. There were no specific recommendations with regards to the timing of screening in relation to surgical procedures. Coia et al.25 published guidelines for the prevention and control of MRSA in healthcare facilities in 2006. The guidelines were based on a systematic review of the literature, and each recommendation was graded according to the US Centers for Disease Control Advisory Committee system for categorizing recommendations. The grading recommendation system is shown in Table 8. Table 8: US Centers for Disease Control Advisory Committee system for categorizing recommendations used by Coia et al.25 Category Recommendation

1a Strongly recommended for implementation and strongly supported by well-designed experimental, clinical, or epidemiological studies.

1b Strongly recommended for implementation and strongly supported by certain experimental, clinical, or epidemiological studies and a strong theoretical rationale

1c Required for implementation, as mandated by federal or state regulation or standard. The UK equivalent is to operate within European Union or UK Health and Safety Legislation

2 Suggested for implementation and strongly supported by suggestive experimental, clinical, or epidemiological studies or a theoretical rationale

No recommendation Unresolved issue. Practices for which insufficient evidence exists or for which

Pre-operative screening for MRSA 15

Category Recommendation

there is no consensus regarding efficacy The guidelines recommended that active screening for MRSA carriage should be performed and the results linked to a targeted approach to the use of isolation and cohorting facilities (Category 2). Details regarding which patients should be screened should be determined locally and be influenced by local prevalence of MRSA in the hospital and the units concerned, the reason for admission of the patient, the risk status to the unit to which they are admitted, and the likelihood that the patient is carrying MRSA. All patients who are at high risk for carriage should be screened at the time of admission unless they are being admitted directly to isolation facilities (Category 2). Patients who are at high risk of carrying MRSA are: patients previously infected of colonized with MRSA; frequent readmissions; inter-hospital transfers; recent inpatients at hospitals with a high MRSA prevalence; residents of residential care facilities (Category 1b). Units caring for patients at high risk for MRSA or with high proportion of MRSA infection among colonized patients include ICU, neonatal ICU, burn, transplant, cardiothoracic, orthopedic, trauma, vascular surgery, renal, and regional, national and international referral centers. Screening should be done preoperatively for elective procedures if possible, or at time of admission. Decolonization of MRSA-positive patients is recommended for a period of five days, however there is no mention that elective surgery should be scheduled or delayed to complete this process first. A summary of recommendations for screening (populations and timing) in the eight guidelines reviewed in this report is provided in Appendix I. Limitations The lack of controlled randomized studies on the question of MRSA screening effectiveness makes it difficult to draw conclusions regarding a causal relationship between declines in MRSA infection and concurrent screening practices. The observational studies reviewed in this report were susceptible to several biases. It may have been difficult to control for changes in patient management protocols, practices involving antibiotic use, or even physical changes to the hospital setting15 over the course of longitudinal uncontrolled, and often retrospective studies. Furthermore, retrospective assessments have some limitations in detecting outcomes, and follow-up in some studies may have been insufficient to detect infections occurring after the follow up period (often 30 days post-surgery). In addition, as noted by McGingle et al.,8 there may be some publication bias in that negative studies of poorer quality are less likely to be published. Some of the guidelines reviewed did not describe the method used to produce their recommendations. In cases where recommendations were graded, they tended to be based on poorer quality evidence and / or expert opinion. All of the guidelines reviewed were not in agreement with regards to the practice of screening for MRSA in hospitals. CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING: Screening pre-operatively does not appear to be universally accepted or employed as a preventive measure against MRSA infection.19,20,26 This may be due in part to inconclusive evidence regarding the effectiveness of screening and of decolonization procedures.8,20 Among the reports considered for this review, eight observational studies suggested that MRSA screening had a positive impact on MRSA infection,9,10,12-17 one large scale controlled observational study11 found that screening had no impact, a systematic review found that the

Pre-operative screening for MRSA 16

evidence suggested a positive impact of MRSA screening but that the poor quality of the evidence precluded making recommendations, and a model from a health technology assessment concluded that any approach to screening is better than no screening.7 Given the conflicting results of the observational studies, and the bias issues inherent with uncontrolled studies, it is difficult to draw conclusion regarding the efficacy of MRSA screening from these reports. With regards to the timing of pre-operative MRSA screening, most of the observational studies had patients undergo decolonization procedures for 5 days following a positive MRSA test, and while some timed the completion of the decolonization process to occur prior to surgery, 9,10,13 others did not.11,13 Similarly, there was no consistent rule for the timing of screening versus elective surgical procedure in the guidelines that were reviewed. One of the guidelines did specify a preference for screening at least one week prior to admission for elective procedures to allow for 5 days decolonization.21 There was some consistency between guidelines that identified high risk groups for targeted screening.21,24,25 Included were elective admissions, ICU admissions, neonatal units, trauma and burn units, patients with previous positive MRSA cultures, transfers from residential care facilities, and patients from specific high-risk wards (e.g. cardiothoracic, neurosurgery, orthopedic, renal). These and other characteristics have also been identified in the literature.27-30 The guidelines by Coia et al.25 recommended that details regarding which patients should be screened should be determined locally and be influenced by local prevalence of MRSA in the hospital and in the units concerned, the reason for admission of the patient, the risk status to the unit to which they are admitted, and the likelihood that the patient is carrying MRSA. At the present time, the evidence for screening for MRSA in a hospital setting is inconclusive. In the absence of other preventive measures, hospitals may choose to try screening in order to control the spread and incidence of MRSA infection in their facilities. A surveillance system should be in place to monitor changes in incidence of MRSA infection before and after the institution of a screening program. Target populations for screening may be based on high risk groups identified in guidelines or the literature, as well as local characteristics of MRSA infection. The reviewed literature suggests that some practitioners choose to have their MRSA-positive patients start decolonization procedures about a week prior to elective surgery, a process that lasts approximately five days. Further study of the efficacy of MRSA screening and of the efficacy of decolonization procedures is needed. PREPARED BY: Eva Tsakonas, BA, MSc, Consultant Charlene Argáez, MLIS, Information Specialist Health Technology Inquiry Service Email: [email protected]: 1-866-898-8439

Pre-operative screening for MRSA 17

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22. North Yorkshire community infection prevention and control policies and guidance: MRSA. London: North Yorkshire and York, Community and Mental Health Services; 2009. Available: http://www.nyypct.nhs.uk/AdviceInformation/InfectionControl/PoliciesAndGuidance/docs/community/NYYPCT%20&%20NYHHPU%20D8%20MRSA%20IPC%20Policy%20-%20version%201.01%20-%20March%202009.pdf (accessed 2009 Jun 25).

Pre-operative screening for MRSA 19

Pre-operative screening for MRSA 20

23. Methicillin-resistant staphylococcus aureus (MRSA). Kent, England: Cystic Fibrosis Trust; 2008. Available: http://www.cftrust.org.uk/aboutcf/publications/consensusdoc/MRSA_1st_Edition_Final_web.pdf (accessed 2009 Jul 6).

24. Screening for Meticillin-resistant Staphylococcus aureus (MRSA) colonisation: a strategy for NHS trusts - a summary of best practice. London: Department of Health, National Health Service (NHS), Great Britain; 2006 Nov 15. Product number 277346. Available: http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_063188?IdcService=GET_FILE&dID=66867&Rendition=Web http://www.clean-safe-care.nhs.uk/toolfiles/106_281812SCR_MRSA_screening.pdf (accessed 2008 Nov 27).

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Appendix 1: Summary of guideline recommendations for timing of pre-operative screening, and populations to be screened Author (year) Country Patient

population Timing of pre-

operative screening

Patient population to be screened

Comment

Institute for Clinical Systems Improvement 18 (2009)

United States Perioperative / surgical

Not indicated that screening is part of protocol

NS Management of MRSA at patient arrival (not at pre-operative evaluation) and during perioperative period noted, but no details on whether this involved a clinical assessment or screening are provided.

Chelsea and Westminster Hospital (NHS)21 (2009)

United Kingdom

In-patient Preferably in pre-operative assessment or out-patient clinic at least one week before admission for elective procedures to allow for 5 days of decolonization; on admission for emergency surgical patients; prior to surgery for any emergency patient who is scheduled for surgery but is already an inpatient.

Elective admissions; admissions to ICU, neonatal units, and burn units; admissions from ICU; transfer from wards with suspected MRSA outbreaks; patients with previous admissions of ≥1 nights; patients with past MRSA infection; transfers from residential care facilities. Do not screen during topical eradication and during treatment (and for 2 days after) with antibiotics.

North Yorkshire and York Community and Mental Health

United Kingdom

Community and in-hospital

Not stated, however 5-day decolonization and eradication

All planned admissions to hospital

Pre-operative Screening for MRSA 21

Author (year) Country Patient

population Timing of pre-

operative screening

Patient population to be Comment screened

Services (NHS)22 (2009)

program recommended

Cystic Fibrosis Trust23 (2008)

United Kingdom

Cystic fibrosis patients

At each hospital visit, or on or before admission to hospital with a view to implementing a decontamination program

Screening of CF patients at respiratory sites for MRSA at each hospital visit, and at non-respiratory sites on or before admission to hospital for elective procedures

This recommendation was given a C grade, indicating that it was based on expert opinion and/or studies of poor quality.

Massachusetts Department of Public Health19 (2008)

United States Perioperative / surgical

NS NS Although this guideline addresses preoperative preparation of the patient, there is no recommendation for screening. In addition, there is no recommendation for or against the pre-operative use of mupirocin to reduce post-surgical nosocomial infection, due to inconclusive evidence of this treatment’s efficacy.

Anderson et al.20 (2008)

United States Perioperative / surgical

NS NS The routine screening for MRSA or routine attempts to decolonize surgical patients in the preoperative setting has been flagged as an unresolved issue in this guideline. This is based on inconclusive evidence from a 4000-patient trial (Harbarth et al.11 and subsequent secondary analysis of mupirocin, both published by

Pre-operative Screening for MRSA 22

Author (year) Country Patient

population Timing of pre-

operative screening

Patient population to be Comment screened

Perl et al. in 2002, as well as from positive but methodologically weak (non RCT) data on same treatment.

London Department of Health (NHS)24 (2006)

United Kingdom

In-hospital Preoperatively, or at time of admission

Preoperative surgical patients in certain surgical specialties, particularly orthopedics, cardiothoracic, and neurosurgery; emergency orthopedic or trauma admissions; ICU and high dependency unit (HDU) patients; renal patients; patients with previous MRSA-positive culture; all elective surgery patients; oncology/chemotherapy patients; patients admitted from high-risk settings such as nursing homes; and all emergency admissions.

Coia et al.25 (2006)

United Kingdom

In-hospital Preoperatively for elective procedures if possible, or at time of admission

Active screening should be performed and the results linked to a targeted approach to the use of isolation and cohorting facilities (Category 2). Details regarding which patients should be screened should be determined locally and be influenced by local prevalence of MRSA in the hospital and the units concerned, the reason for admission of the patient, the risk status to the unit to which they are admitted, and the likelihood that the patient is carrying MRSA. All patients who are at high risk for carriage should be screened at the

Decolonization of MRSA-positive patients is recommended for a period of five days, however there is no mention that elective surgery should be scheduled or delayed to complete this process first.

Pre-operative Screening for MRSA 23

Author (year) Country Patient

population Timing of pre-

operative screening

Patient population to be Comment screened

time of admission unless they are being admitted directly to isolation facilities (Category 2). Patients who are at high risk of carrying MRSA are: patients previously infected of colonized with MRSA; frequent readmissions; inter-hospital transfers; recent inpatients at hospitals with a high MRSA prevalence; residents of residential care facilities (Category 1b). Units caring for patients at high risk for MRSA or with high proportion of MRSA infection among colonized patients include ICU, neonatal ICU, burn, transplant, cardiothoracic, orthopedic, trauma, vascular surgery, renal, and regional, national and international referral centers.

NS: not stated; NHS: National Health Service; RCT: randomized controlled trial; ICU: intensive care unit; HDU: high dependency unit; Category 1b recommendation: Strongly recommended for implementation and strongly supported by certain experimental, clinical, or epidemiological studies and a strong theoretical rationale; Category 2 recommendation: Suggested for implementation and supported by suggestive experimental, clinical, or epidemiological studies or a strong theoretical rationale.

Pre-operative Screening for MRSA 24