Multicentre assessment of linezolid antimicrobial activity and spectrum in Europe: Report from the Zyvox® antimicrobial potency study (ZAPS-Europe)

Abstract

Objective. To evaluate the in vitro spectrum and activity of linezolid, a recent oxazolidinone, according to well-controlled surveillance data from 42 medical centers in 13 countries throughout Europe. Methods. Participants tested the susceptibility of 125 clinical strains of enterococcal and staphylococcal species against 13 drugs using reference broth microdilution trays or the standardized disk diffusion method of the National Committee for Clinical Laboratory Standards (NCCLS). Streptococcal species (n=25 at each center) were tested against six drugs using E test (AB BIODISK, Solna, Sweden). Quality assurance testing was conducted using NCCLS-recommended strains and verification of resistance to linezolid and other selected agents was performed by retesting strains at the regional (Europe) and international (USA) monitor sites. Results. A total of 5598 strains from throughout Europe (91% compliance) were tested. Vancomycin resistance was reported in only 0.6 and 3.0% of Enterococcus faecalis and E. faecium, respectively. Penicillin resistance occurred in 25.1% of Streptococcus pneumoniae; 4.9% at the high-level (≥2 mg/L). The MIC90 for linezolid was 1 mg/L for streptococci and 2 mg/L for enterococci and staphylococci. Using the US FDA- and EUCAST-recommended susceptible breakpoints for linezolid, there were no confirmed reports of linezolid resistance [minimum inhibitory concentration (MIC), ≥8 mg/L]. The distribution of linezolid MIC values was unimodal and varied between 0.25 and 1 mg/L for streptococci (>90% of isolates), and between 1 and 2 mg/L for staphylococci (>90%) and enterococci (>95%). There were no differences in linezolid susceptibility in the vancomycin-, oxacillin-, or penicillin-resistant subsets of strains when compared to susceptible organism populations. Conclusions. Compared to the North American component of this study, there was substantially less vancomycin resistance among E. faecium isolates (Europe 3.0% vs. North America 63.4%). While the occurrence of penicillin-resistant S. pneumoniae in Europe and North America was similar (25.1% vs. 29.7%), the recovery of high-level penicillin-resistant strains was nearly three-fold higher in North America (4.9% vs. 13.2%). Only linezolid was universally active against all the tested Gram-positive isolates at ≤4 mg/L.