Trends in linezolid susceptibility patterns: report from the 2002-2003 worldwide Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program

Linezolid is an important oxazolidinone antimicrobial for the treatment of infections caused by Gram-positive cocci, especially vancomycin-resistant enterococci and oxacillin-resistant Staphylococcus aureus (ORSA). Since its introduction, however, ribosomal mutations have been detected that produce resistance; thus, longitudinal surveillance remains necessary to monitor for emerging resistance in all geographic areas of oxazolidinone use. The 2003 Zyvox® Annual Appraisal of Potency and Spectrum (ZAAPS) Program compared linezolid minimum inhibitory concentration (MIC) results with 13-15 comparator antimicrobial agents (8089 isolates) and also with results from an earlier surveillance period (2002). Sampling institutions in the United States of America (USA), Canada, Europe (seven nations), South America (three nations) and the Asia-Pacific (three nations) referred 200 Gram-positive cocci to the central laboratory for MIC processing and identification confirmation. Linezolid resistance (MIC ≥ 8 mg/L) was established by alternative susceptibility testing methods as well as by ribosomal target characterisation. Concurrent drug use data were collected. Linezolid activity against the six major organism groups did not vary between years or geographic areas. In contrast, penicillin resistance increased 2% in Streptococcus pneumoniae; macrolide resistance was stable among β-haemolytic streptococci (19-21%), but increased in S. pneumoniae (+2%); ORSA rates increased 4%; and vancomycin resistance in enterococci was present, but varied markedly by region. Non-clonal linezolid-resistant isolates were detected, each having the same G2576U 23S rRNA target mutation. Furthermore, the first linezolid-resistant, non-USA isolate (S. aureus in Greece) was observed, apparently related to linezolid use. In 2003, near complete activity for linezolid against Gram-positive isolates was again documented (99.93% susceptible) in the ZAAPS Program. Rare linezolid-resistant isolates were identified among enterococci, limited to USA strains. Limited correlations of linezolid resistance to drug use continues, with an average consumption rate of 0.63 DDD/100 patient days (a 50% increase since 2002), and indicates the important role of hospital hygiene practice in preventing the dissemination of oxazolidinone resistances, should they be detected.