Stability of linezolid activity in an era of mobile oxazolidinone resistance determinants: results from the 2009 Zyvox® Annual Appraisal of Potency and Spectrum program

Abstract

Linezolid is the only oxazolidinone agent approved for clinical use and has been administered to millions of patients over nearly a decade, becoming an important therapeutic alternative for infections caused by multidrug-resistant (MDR) Gram-positive pathogens. Resistance is due to mutations in 23S rRNA and the ribosomal proteins L3 and L4 and, more recently, the mobile cfr gene (causes resistance to several antimicrobial classes). Using reference broth microdilution methods in a central reference laboratory design, MIC values were obtained during the 2009 Zyvox® Annual Appraisal of Potency and Spectrum program (5754 sampled strains from 22 countries), and the following MIC 90 values were obtained for the leading pathogen or species groups: Staphylococcus aureus (2 μg/mL), coagulase-negative staphylococci (CoNS; 1 μg/mL), Enterococcus spp. (2 μg/mL), and 3 groups of streptococci (1 μg/mL) including Streptococcus pneumoniae. Linezolid-resistant strains (8 or 0.14% overall) that were not Staphylococcus aureus were observed in 5 nations and included CoNS (0.48%) having the mobile cfr gene. The results of this study demonstrate that linezolid continues to be effective in vitro against MDR pathogens, and the resistance rates appear stable.