| Abstract: | Methicillin-resistant Staphylococcus aureus (MRSA) is being seen with greater frequency in most hospitals and other health care facilities across Canada. The organism may cause life-threatening infections and has been associated with institutional outbreaks. Several studies have confirmed that MRSA infection is associated with increased morbidity and mortality compared with infections caused by susceptible strains, even when the presence of comorbidities is accounted for. Treatment of MRSA infection is complicated by the fact that these organisms are resistant to multiple antimicrobial agents, so treatment options are limited. The effectiveness of decolonization therapy (attempting to eradicate MRSA carriage) is also uncertain. This paper reviews the medical management of MRSA infections, discusses the potential role of decolonization and provides an overview of evidence to support recommended infection control practices.Key Words: Methicillin resistance, MRSA, Staphylococcus aureusThe past few decades have witnessed the emergence of methicillin-resistant Staphylococcus aureus (MRSA) as a major hospital-acquired pathogen worldwide (1-4). Although MRSA was first reported in Canada in 1981 (5), MRSA rates in Canadian hospitals have only increased substantially in the last few years. The Canadian Nosocomial Infection Surveillance Program (CNISP) reported that the incidence of MRSA in sentinel hospitals across the country increased from a mean of 0.9 per 100 S aureus isolates in 1995 to 8.2 per 100 isolates in 2001, and from 0.5 cases per 1000 admissions in 1995 to 4.4 per 1000 admissions in 2001 (6,7). Part of this increase may have been related to more frequent screening for MRSA colonization in high risk patients (8). However, a fourfold increase in MRSA infection rates was also observed (from 0.3 infections per 1000 admissions in 1995 to 1.2 infections per 1000 admissions in 2001) (6,7)Although there have been recent reports describing community-onset MRSA in the United States, CNISP data would suggest that MRSA remains predominantly a hospital-acquired pathogen in Canada (6). Nevertheless, it would seem reasonable to expect that an increase in MRSA rates in hospitals will eventually lead to spread of the organism in long term care facilities and the community. In Canada, community-acquired MRSA has been reported most frequently in western Canada, especially among native Aboriginals and intravenous drug users (9,10). Recognized risk factors for MRSA acquisition have included previous hospitalization, admission to an intensive care unit, prolonged hospital stay, proximity to another patient with MRSA, older age, invasive procedures, presence of wounds or skin lesions, and prior antimicrobial therapy (11-15).If MRSA only colonized patients, there would be little reason for concern. However, 20% to 60% of patients identified as being colonized with MRSA in hospital subsequently develop an MRSA infection (12). Using standard criteria for identification of infections, CNISP data indicated that approximately 31% of patients with MRSA in Canadian hospitals were infected (7). In certain high risk populations, staphylococcal infections including bacteremia occur more frequently following colonization with MRSA than after colonization with susceptible strains of S aureus (16). Moreover, MRSA does not merely replace susceptible strains of S aureus as a hospital-acquired pathogen, but rather, it appears to add substantially to the total burden of nosocomial infections (17,18). Although the results are somewhat controversial, several studies have also indicated increased mortality and prolonged hospitalization associated with MRSA infections (19-21). After adjustment for comorbidities, methicillin resistance has been found to be a significant independent risk factor for mortality in bacteremic patients (21-23).Several studies have also documented the economic impact of MRSA in hospitalized patients, demonstrating increased costs associated with managing infections and with the implementation of control measures (19,24,25). The average attributable cost of managing an MRSA infection in a Canadian hospital was estimated to be approximately $14,360, whereas costs associated with managing a patient with MRSA colonization were approximately $1,363 per hospital admission (25).The first strain of S aureus, an MRSA, with reduced susceptibility to vancomycin was reported from Japan in 1996 (26,27). Since then, such strains with vancomycin minimum inhibitory concentrations (MIC) of 8 μg/mL to 16 μg/mL (vancomycin-intermediate S aureus [VISA]) have been reported from several countries in southeast Asia, South America, Europe and the United States (28-30). Of even greater concern has been the recent identification of two infections caused by MRSA with high level resistance to vancomycin (MIC greater than 128 μg/mL; vancomycin-resistant S aureus [VRSA]), mediated by the vanA gene determinant found in vancomycin-resistant enterococci (31,32). These developments have emphasized the need for appropriate use of glycopeptides and other antimicrobial agents in the management of patients with MRSA. This paper reviews options for the treatment of patients with MRSA infection or colonization. The treatment options should be considered appropriate for hospitalized patients as well as for out-patients, and for those residing in long term care facilities. |
