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

Introduction

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 of 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 1,000 admissions.³ In 2007, the estimated rate of MRSA infection in Canadian hospitals remained approximately the same (5.87 cases per 1,000 admissions), and 4,728 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 its patients. The efficacy of this preventive measure, and the identification of which populations should be screened (global versus targeted), have been subjects of some debate.{2357} 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.{2357}

This review was conducted with the aim of informing decisions regarding MRSA screening in health care facilities, by specifically reviewing the recent evidence for the efficacy of hospital-based MRSA screening programs, identifying which patient populations are recommended to be included in a screening program, and summarizing recommendations for the timing of screening relative to surgical procedures.

Objective

The objective of the report is to answer the following research questions:

• What is the clinical effectiveness of pre-operative MRSA screening?

• What are the guidelines for the timing of pre-operative MRSA screening?

• Is there evidence to guide the selection of patients who should be screened pre-operatively for MRSA?

Methods

A limited literature search was conducted on key health technology assessment (HTA) resources, including PubMed, The Cochrane Library (Issue 2, 2009), the University of York Centre for Reviews and Dissemination (CRD) databases, ECRI, EuroScan, and 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 handsearching 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 handsearch. From these 108 references, 35 reports were retrieved for further assessment. These reports included: HTAs, 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 with 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.

Health Technology Inquiry Service 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.

Results

One HTA,⁷ one systematic review,⁸ nine observational studies,^9–17 and eight practice guidelines^18–25 were identified. No randomized controlled trials were identified.

Health Technology Assessments

The National Health Service in Scotland published an HTA of the clinical effectiveness and cost-effectiveness of screening for MRSA in acute inpatient hospital settings in 2007.⁷ Because UK guidelines provided contradictory recommendations of the MRSA screening process, as well as the targeted screening patient populations, an assessment was commissioned to consider the different MRSA screening strategies and appropriate management of patients found to be colonized with MRSA.

The authors noted several limitations with the studies and the data included in the 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 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 who are in isolation for MRSA infection treatment.

Systematic Reviews

A systematic review⁸ of the use of active surveillance cultures (ASCs) in adult intensive care units (ICUs) to reduce MRSA-related morbidity, mortality, and costs in 2008 identified 16 observational studies (only two of which had a control group) and four economic reports. All selected studies were assessed for quality and internal validity. None of them was 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. 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 conclude that the evidence from multiple observation-based studies suggests that the use of ASCs reduces the incidence of MRSA infection, but because of the overall poor quality of the evidence, definitive evidence-based recommendations cannot 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

The authors of a study⁹ that looked at the impact of best practices and active surveillance screening for MRSA on the reduction of MRSA surgical site infections concluded that surveillance for MRSA and eradication of the carrier state reduces the rate of MRSA surgical site infections. They recommended further prospective studies at a range of health care institutions to evaluate the value of this approach to MRSA infection management.

Another study¹⁰ reported on the effectiveness of pre-operative screening and the treatment of MRSA in otolaryngological surgical practice at a US hospital in 2009 and found that early results show the potential benefit of pre-operative S. aureus screening in MRSA infection rate reduction, but that larger studies in this area are needed.

A study¹¹ of the effect of an early MRSA detection strategy on hospital MRSA infection rates in surgical patients in 2008 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, a study¹² was published 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 found 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 surgical site infections.

The authors of a before-and-after study¹⁷ on the effect of two expanded surveillance interventions on MRSA 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 study¹³ of the impact of rapid PCR screening for MSRA in nine specialty wards of the University College London Hospitals, in which routine screening for MRSA was not previously conducted, found that rapid MRSA screening of all surgical admissions resulted in a significant reduction in S. aureus bacteremia during the screening period, although a causal link could not be established.

The authors of a case-control study¹⁴ that assessed the impact of screening and antibiotic prophylaxis on preventing MRSA infection in percutaneous endoscopic gastrostomy in 2007 concluded that an active screening decontamination and antibiotic prophylaxis protocol identifies cases of MRSA colonization in patients undergoing percutaneous endoscopic gastrostomy tube placement and can significantly reduce the risk of peristomal percutaneous endoscopic gastrostomy site infections.

In 2006, a study was published¹⁵ that looked at the effectiveness of active screening for MRSA in high-risk units in a 400-bed US hospital. The authors concluded that even in a setting of increasing community-associated MRSA, active MRSA screening as a part of a multifaceted intervention targeted to high-risk units may be an effective strategy for achieving a sustained decrease in MRSA infections throughout the hospital.

The authors of a 2005 study¹⁶ that prospectively compared rates of hospital-acquired MRSA infection in patients undergoing hip and knee replacement surgery, before and after the institution of a program for compulsory MRSA swabbing at one UK hospital, 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, three^18–20 did not recommend pre-operative screening for MRSA and two of the guidelines^19,20 indicated that the evidence for decolonization using mupirocin was inconclusive. One guideline¹⁸ recommended the 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 US. The remaining five guidelines in this review recommended screening for MRSA, and all of the five originated in the UK.^21–25

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 treatment 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, 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

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 evidence suggested a positive impact of MRSA screening, but that the poor quality of the evidence precluded making recommendations; and a model from an HTA 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.

Regarding the timing of pre-operative MRSA screening, most of the observational studies had patients undergo decolonization procedures for five days following a positive MRSA test, and while some timed the completion of the decolonization process to occur before 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 before admission for elective procedures to allow for five days of 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 One set of guidelines²⁵ 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 to control the spread and incidence of MRSA infection in their facilities. A surveillance system should be in place to monitor changes in the 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 MRSA-positive patients start decolonization procedures about a week before 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.

[Adapted from Tsakonas E, Argáez C. Pre-Operative Screening for Methicillin-Resistant Staphylococcus aureus (MRSA) Infection: A Review of the Clinical-Effectiveness and Guidelines. (Health Technology Inquiry Service). Ottawa: Canadian Agency for Drugs and Technologies in Health; 2009.]