Characterization of Baseline Methicillin-Resistant Staphylococcus aureus Isolates Recovered from Phase IV Clinical Trial for Linezolid

Abstract

A total of 565 methicillin-resistant Staphylococcus aureus (MRSA) isolates were collected mostly from Europe and the Americas (2004 to 2007) during a phase IV clinical trial comparing linezolid with vancomycin for the treatment of complicated skin and skin structure infections proven to be due to MRSA. The isolates were tested for their susceptibilities by the broth microdilution method, they were tested for inducible clindamycin resistance by the D-test, and they were screened for heterogeneous resistance to vancomycin (heterogeneously vancomycin-intermediate S. aureus [hVISA]) by the Etest macromethod. The isolates were evaluated for the MRSA genotype by pulsed-field gel electrophoresis, staphylococcal protein A (spa) typing, multilocus sequence typing (MLST), and staphylococcal cassette chromosome mec (SCCmec) typing. All isolates were inhibited by 4 microg/ml of linezolid (MIC(50) and MIC(90), 2 and 4 microg/ml, respectively). The vast majority of isolates (92.4%) were resistant to erythromycin, and high clindamycin resistance rates were observed (28.5% constitutive and 16.3% inducible). Only 1.0% of the isolates were hVISA. Isolates from the United States were predominantly USA300 sequence type 8 (ST8)-SCCmec type IV (78.5%), followed by a lower prevalence of USA100 ST5-SCCmec type II isolates (14.2%). Strains belonging to the ST5 lineage were widely distributed in Portugal, South American countries, and Mexico. MRSA strains belonging to ST8-SCCmec type IV predominated in Russia (80.0%) and also emerged in Venezuela and Colombia. The epidemic MRSA type 15 clone predominated in the United Kingdom (55.6%) and Spain (100%). In addition, a new MLST profile (ST1071) was observed in South Africa. This study demonstrated the presence of major clones in particular regions (ST8 in the United States, ST5 in Latin America and Portugal, ST22 in Spain and the United Kingdom); however, emerging clones were identified, suggesting that the epidemiology of MRSA continues to evolve.