Preventing MRSA Infections: Title and subTitle BreakFinding It Is Not Enough

Each year, an estimated 1.7 million individuals in the United States acquire an infection while hospitalized, resulting in nearly 100 000 deaths¹ and an additional $6.5 billion in health care expenditures.² Many of these infections are caused by antimicrobial-resistant organisms, and methicillin-resistant Staphylococcus aureus (MRSA) ranks among the most prevalent pathogens in hospitals worldwide. MRSA is easily transmitted in the health care setting and is a frequent cause of hospital outbreaks. A 2004 evaluation found that one-quarter of US hospitals reported at least 1 MRSA outbreak in the prior year.³ As Centers for Disease Control and Prevention (CDC) investigators reported in a recent article, more than 18 000 deaths were estimated to have occurred among patients with invasive MRSA infections in the United States during 2005, with most of the infections associated with health care delivery.⁴

For every person infected with MRSA, many more are colonized with the organism—a 2004 National Health and Nutrition Examination Survey estimates that 1.5% of US residents, or more than 4 million individuals, carried MRSA in their anterior nares, the most common site of S aureus carriage.⁵ Carriers of MRSA are at higher risk of MRSA infection than are noncarriers. Davis et al⁶ found that 25% of individuals who acquire MRSA colonization during a hospital stay subsequently develop MRSA infection. Patients who acquire MRSA while hospitalized also serve as reservoirs for MRSA transmission in the community. The ongoing spread of the community-associated USA300 strain of MRSA⁴ is a reminder that MRSA is no longer just a hospital problem.

MRSA prevention strategies in hospitals have focused primarily on preventing cross-transmission and include improved hand hygiene practices, environmental cleaning and disinfection,⁷ timely identification of MRSA-colonized patients, and management of MRSA-infected or -colonized patients under contact (barrier) precautions. One method to increase the detection of asymptomatic colonized patients is active surveillance culturing (ASC), which involves obtaining cultures, typically from patients' nares, at the time of hospital admission and is intended to detect MRSA carriers so that contact precautions can be instituted in a timely manner to reduce the likelihood of transmission to other patients.

Some infection control experts, policy makers, legislators, and consumer groups increasingly argue that ASC should be used routinely, calling for universal screening of all hospital admissions in an attempt to stem the rising tide of MRSA infections in hospitals. Several large hospital organizations, including the Veterans Affairs Health Administration Hospitals and both Evanston Northwestern Healthcare and Loyola University Medical Center in the Chicago area, now screen all hospital admissions for MRSA. The Institute for Healthcare Improvement's 5 Million Lives Campaign has called for wider application of ASC for MRSA.⁸ New legislation in Illinois mandates MRSA screening of all high-risk hospital admissions, and similar legislation has been introduced or approved in several other states, including Maryland, New Jersey, and Pennsylvania.

Despite the legislative mandates, broad-based application of ASC remains a controversial approach to MRSA control. Implementing ASC is an expensive and complex intervention, fraught with the potential for unintended adverse consequences.⁹ Its use may result in a 2- to 5-fold increase in the number of patients placed under contact precautions,^{10 - 11} potentially subjecting the isolated patients to reduced attention from health care workers^{12 - 13} and increased rates of depression, anxiety, and other adverse effects.^{14 - 16} Furthermore, much of the data supporting ASC come from single hospitals that used multiple interventions during MRSA outbreaks, without use of concurrent control groups.¹⁷ Whether ASC can prevent MRSA infections in hospitals where MRSA is endemic but where infection rates are stable or low remains an unresolved issue.

In this issue of JAMA, Harbarth and colleagues¹⁸ offer a valuable assessment of ASC in just such an endemic setting. Using a prospective crossover design and a rapid detection test to ensure that screening results would be available in a timely manner, the authors found that adding ASC to standard infection control measures did not reduce nosocomial MRSA infection rates in a surgical population. This study represents the largest controlled trial of ASC for MRSA control. Despite the detection and isolation of more than 300 previously unidentified MRSA carriers during the intervention periods, the observed rate of nosocomial MRSA infection was unchanged. Investigators were also unable to show any reduction in MRSA acquisition during the intervention periods.

In addition, the investigators¹⁸ attempted to assess the effect of changes in perioperative antibacterial prophylaxis (inclusion of an agent active against MRSA) and use of preoperative decolonization (intranasal mupirocin and chlorhexidine bathing) on rates of MRSA surgical site infection. However, despite use of a rapid polymerase chain reaction test, too few MRSA carriers were identified in time to implement these measures, making it impossible to assess effectiveness. Other limitations include that the investigators did not screen all hospital admissions and did not screen patients weekly and on hospital discharge, as suggested by proponents of ASC. Patients not screened, including those who acquired MRSA colonization during hospitalization, were therefore not detected and not placed under contact precautions.

The results of this study support current CDC guidelines and a recent infection control position statement that recommends against the routine or mandated use of ASC for MRSA control.^{7 ,19} As Harbarth et al¹⁸ point out, the local epidemiology of MRSA differs greatly from one hospital to the next. Hence, there exists no one-size-fits-all solution to the problem of MRSA prevention.

Although MRSA has been a major hospital problem for more than 4 decades, an enormous need remains for research to help inform MRSA prevention efforts. Well-designed and carefully controlled trials of different approaches are needed. Such studies should compare enhanced use of standard infection control practices to strategies that include combinations of ASC, contact precautions, environmental decontamination, and eradication of MRSA colonization. Novel approaches such as active or passive immunization against S aureus may hold promise for prevention. Better understanding is needed about the potential unintended adverse consequences of current control strategies (eg, contact precautions) and how to ameliorate them. In an era of increasing health care costs, it will also be important to consider the cost-effectiveness of proposed approaches.

While awaiting more and better data, what should clinicians do to control MRSA in hospitals? The first part of a tiered approach should include careful assessment of MRSA within the local health care environment. Hospitals should first adhere to established infection control principles and pursue patient safety initiatives known to reduce morbidity and mortality from all health care–associated infectious pathogens. Despite the attention rightly focused on MRSA, this pathogen causes only 8% of hospital-acquired infections in the United States, according to the most recent data from the National Healthcare Safety Network (S. K. Fridkin, MD, written communication, January 29, 2008). Interventions that will address those 8% plus the other 92% of hospital infections include intensive and multifaceted hand hygiene programs²⁰ ; “bundled” interventions to reduce central venous catheter–related bloodstream infections,²¹ ventilator-associated pneumonia,²² and surgical site infections²³ ; and “source control” in the form of chlorhexidine bathing of intensive care unit patients.²⁴ These interventions are simple and cost-effective and have the benefit of reducing all infections, including those due to MRSA. If health care–associated infections can be reduced to near zero with bundled interventions, MRSA infection rates should fall concordantly. One hospital using these population-based (rather than “MRSA-based”) interventions has reported a more than 70% reduction in MRSA infections in its intensive care units over a 4-year period.²⁵ A second tier of interventions should be implemented when these interventions fail to reduce infection rates and during any MRSA outbreak. These interventions are clearly outlined in recent CDC recommendations⁷ but may include intensification of surveillance efforts with the use of ASC and decolonization.

Achieving lower rates of MRSA infections in hospitals is possible by attending to basic infection control principles and other proven interventions. However, as evidenced by the study by Harbarth et al, simply expanding the use of ASC might not help achieve the elusive goal of preventing all MRSA infections.