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Controlling the Spread of Healthcare Associated Methicillin Resistant Staphylococcus aureus Requires Active Surveillance

Both methicillin sensitive and methicillin resistant Staphylococcus aureus (MSSA, MRSA) can cause invasive and life-threatening infections such as osteomyelitis, septicemia, endocarditis, and pneumonia. Healthcare associated MRSA is of particular clinical importance because it is not only predictably cross resistant to all penicillins and cephalosporins, but is also typically resistant to multiple other antibiotics. Possibly because of inadequate initial antibiotic treatment, infections with health care associated MRSA result in increased costs and worse outcomes compared to infections with MSSA.

Methicillin was introduced in 1959, and as early as 1961 MRSA strains were being reported. Since then, MRSA has become increasingly prevalent worldwide, and in the past decade or more has increased dramatically in North America, Australia, and many European countries. A recent US hospital survey by the National Nosocomial Infections Surveillance System estimates that 55% of Staphylococcus aureus isolates are methicillin resistant, with the prevalence of MRSA strains being almost as high in non-ICU as in ICU settings. MRSA is also common in long-term care facilities.

MRSA may colonize mucosal or epithelial surfaces, the most common colonized site being the anterior nares. Sites of colonization are important not only as a source of subsequent infection, but also serve as a reservoir for transmission. Although frequent antibiotic use in healthcare settings selects for resistant flora, genetic evidence suggests that virtually all patients with MRSA acquire it from an external source. Patient to patient spread is most frequently caused by health care providers after direct contact with patients.

In January 2000, the Society for Healthcare Epidemiology of America (SHEA) Board of Directors made reducing antibiotic-resistant infections a strategic SHEA goal. SHEA guidelines include active screening of patients for MRSA and implementation of co ntact precautions for colonized or infected patients.

Although screening for colonization with MRSA is of major importance in limiting its nosocomial spread, the standard techniques for MRSA detection, including molecular biology based methods, have required a culture step and isolation of pure colonies. Culture and selection of pure colonies entail a high level of technical training and judgment and may take up to 96 hours for results.

In 2004 two screening methods for the direct detection of nasal colonization by MRSA were approved for marketing in the US by the FDA. Both methods are performed on nasal swab specimens. A third method for direct MRSA detection on nasal swabs is in the final stages of development in the United Kingdom, and is projected for launching in the UK in the second quarter of 2005.

BBL CHROMagar MRSA (BD Diagnostics), utilizes culture on a selective and differential medium. The nasal swab specimen is directly inoculated to the plate for streaking and the plates are incubated for 24 to 48 hours. The agar permits the direct detection and identification of MRSA through the incorporation of specific chromogenic substrates and cefoxitin. MRSA colonies appear mauve on the chromagar, whereas other colonies are either inhibited or produce a distinctly different color. In a nasal swab surveillance study the manufacturer reports a sensitivity and specificity of 95.7% and 97%, respectively, when compared to the gold standard of PCR detection of the mecA gene. In an independent clinical evaluation, Flayhart et al reported a sensitivity and specificity of 99.5% and 98% respectively, when clinical samples were tested on CHROMagarTM and compared to culture on conventional media.

IDI-MRSA (Infectio Diagnostic, Inc.), utilizes PCR for the amplification of MRSA DNA and fluorogenic target-specific hybridization probes for the detection of the amplicons. Nasal swab specimens are placed directly in sample preparation b uffer, and after additional processing, an aliquot of the specimen is added to PCR reagents containing MRSA specific primers. PCR and detection of MRSA amplicons are performed on the Smart Cycler instrument. Processing to detection requires about 1.5 hours. Clinical studies by the manufacturer and an independent investigator report similar sensitivities and specificities of about 92% and 95% respectively, when compared to reference culture techniques.

BacLite MRSA (in development at Acolyte Biomedica Ltd), utilizes culture in a selective broth, followed by bioluminescent detection. Bacteria from nasal swabs are incubated for 3 hours in methicillin-containing broth. Staphylococcus aureus-specific magnetic beads are used to capture intact MRSA, and after a wash step, the MRSA are detected by adenylate kinase bioluminescence. The assay can be completed in less than 5 hours. To date sensitivity and specificity from clinical studies have not been reported.

- Helen Londe, MD

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