title: A multicenter evaluation of linezolid antimicrobial activity in North America.
abstract: Overall, 141 centers in North America enrolled in this international surveillance study designed to evaluate the in vitro antimicrobial activity and spectrum of linezolid, a new oxazolidinone. Each participant tested the susceptibility of clinical isolates of staphylococcal species (n = 85) against 12 drugs, and enterococcal species (n = 40) against 6 drugs using reference broth microdilution trays; and of streptococcal species (n = 25) against 6 drugs using Etests (AB BIODISK, Solna, Sweden). Quality control testing was conducted using recommended strains, and verification of resistance to linezolid and select other agents was performed by a regional monitor. Of the 20,161 isolates collected from sites across the United States (US; n = 132) and Canada (n = 9), 18,307 were included in this analysis. Oxacillin resistance occurred in 38.7 and 70.6% of Staphylococcus aureus and coagulase-negative staphylococcal (CoNS) isolates, respectively. Vancomycin resistance was reported in 65.9 and 2.6% of Enterococcus faecium and E. faecalis, respectively. Penicillin resistance occurred in 37.2% of Streptococcus pneumoniae, 17.5% constituting high-level resistance (MIC, > or =2 microg/ml). The MIC(90) for linezolid was 1 microg/ml for streptococci, 2 microg/ml for enterococci and CoNS isolates, and 4 microg/ml for S. aureus. Using the US FDA-recommended susceptible breakpoints for linezolid, there were no confirmed reports of linezolid resistance (i.e., MIC > or =8 microg/ml). The occurrence of linezolid MICs was unimodal and generally varied between, 1-4 microg/ml for staphylococci (94% of recorded results), 1-2 microg/ml for enterococci (93%), and 0.5-1 microg/ml for streptococci (85%). Susceptibility to linezolid was not influenced by susceptibility to other antiicrobials such as vancomycin, beta-lactams or macrolides. Only linezolid was universally active against essentially all tested Gram-positive specimens. The unimodal susceptibility pattern is indicative of excellent and near complete activity against key Gram-positive pathogens including multiply resistant strains, but surveillance for emerging resistances (rare) and the performance of routine susceptibility tests to guide patient therapy seems prudent.
authors.affiliation: Buffalo Clinical Research Center, NY, USA. cballow@buffalocrc.org
authors.forename: Charles H
authors.initials: CH
authors.lastname: Ballow
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Biedenbach
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D006095:Gram-Positive Cocci / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D009656:North America; D023303:Oxazolidinones / Q000494:pharmacology*; D013045:Species Specificity; D013379:Substrate Specificity
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D000069349:Linezolid