Fast-Track Communication USA600 (ST45) Methicillin-Resistant Staphylococcus aureus Bloodstream Infections

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a major source of invasive infections, implicated in 18,000 deaths annually (9). Mortality rates of 20 to 30% for patients with MRSA bloodstream infections (BSIs) have been reported, with a recent study, spanning 15 years, reporting a mortality rate of approximately 28% (11, 12, 17). Recently, we reported 60% mortality for a small number of MRSA BSIs caused by the USA600 strain type, suggesting that this strain may have unique virulence characteristics (5). USA600, or ST45, first reported as an epidemic strain spreading throughout Germany and the Netherlands in the last decade, has not been associated previously with serious infection (19–21). Given our preliminary findings, we investigated a series of consecutive cases of USA600 MRSA BSI to describe patient-, treatment-, and strain-related characteristics of the infections. Pulsed-field gel electrophoresis (PFGE) analysis of 420 consecutive MRSA bloodstream isolates was performed, and 16 patients with USA600 MRSA BSIs were identified between July 2005 and July 2008 at a 900-bed tertiary care hospital in Detroit, MI (Fig. 1). During the study period, 65% of all S. aureus infections were caused by MRSA. The source of the BSI was identified by chart review using a combination of clinical and laboratory findings and other diagnostic tests according to CDC definitions (7). Epidemiologic classification was conducted based on the presence or absence of health care risk factors and determination of whether the infection was community or hospital acquired, as described previously (8a). The Acute Physiology and Chronic Health Evaluation II (APACHE II) score was calculated for each patient upon presentation of infection (10). Thirty-day mortality was defined as mortality occurring within the 30 days following collection of the index culture sample. Microbiologic failure was defined by the growth of MRSA in a blood culture 10 days after collection of the index culture sample, while the patient was still on therapy. Clinical failure was defined by 30-day mortality and/or microbiologic failure. According to similar definitions, the overall clinical failure rate for patients with MRSA BSIs at our institution during the study period was 23% (5). Each USA600 isolate underwent PFGE, staphylococcal cassette chromosome mec element (SCCmec), and agr typing and testing for Panton-Valentine leukocidin (PVL) as described previously (3, 4). In vitro susceptibility testing was performed according to standards set by the Clinical and Laboratory Standards Institute (4). Vancomycin MICs were determined by Etest (bioMerieux, Durham, NC) and manual broth microdilution (BMD) (4). Vancomycin minimal bactericidal concentrations (MBCs) were determined using previously established methods (4, 14), and vancomycin tolerance was defined by an MBC/MIC ratio of at least 1:32 after 24 h of incubation. Isolates were tested for the heterogeneous vancomycin-intermediate S. aureus (hVISA) phenotype by using the macrodilution Etest (MET; bioMerieux, Durham, NC) as described previously (22). Isolates positive for the hVISA phenotype by this method underwent population analysis as described previously