title: LEADER Program results for 2009: an activity and spectrum analysis of linezolid using 6,414 clinical isolates from 56 medical centers in the United States.
abstract: The LEADER Program monitors the in vitro activity of linezolid in sampled U.S. medical centers using reference broth microdilution methods with supporting molecular investigations in a central laboratory design. This report summarizes data obtained in 2009, the 6th consecutive year of this longitudinal study. A total of 6,414 isolates from 56 medical centers in all nine Census regions across the United States participated in 2009. For the six leading species/groups, the following linezolid MIC(90) values were observed: Staphylococcus aureus, 2 μg/ml; coagulase-negative staphylococci (CoNS), 1 μg/ml; Enterococcus spp., 2 μg/ml; Streptococcus pneumoniae, 1 μg/ml; viridans group streptococci, 1 μg/ml; and beta-hemolytic streptococci, 1 μg/ml. Linezolid resistance was only 0.34% overall, with no evidence of significant increase in the LEADER Program since 2006. The predominant linezolid resistant mechanism found was a G2576T mutation in the 23S rRNA. L3/L4 riboprotein mutations were also found. The mobile multidrug-resistant cfr gene was found in four strains (two S. aureus strains and one strain each of S. epidermidis and S. capitis) from four different states, suggesting persistence but a lack of dissemination. Linezolid continues to exhibit excellent activity and spectrum, and this study documents the need for continued monitoring of emerging mechanisms of resistance over a wide geographic area.
authors.affiliation: JMI Laboratories, North Liberty, IA 52317, USA. david-farrell@jmilabs.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Farrell
authors.forename: Rodrigo E
authors.initials: RE
authors.lastname: Mendes
authors.forename: James E
authors.initials: JE
authors.lastname: Ross
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D016983:Enterococcus / Q000187:drug effects*; D006801:Humans; D020071:Interspersed Repetitive Sequences; D000069349:Linezolid; D008137:Longitudinal Studies; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide; D012338:RNA, Ribosomal, 23S / Q000235:genetics; D013210:Staphylococcus / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects; D013291:Streptococcus / Q000187:drug effects*; D013292:Streptococcus agalactiae / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects; D014481:United States; D034363:Viridans Streptococci / Q000187:drug effects
chemical_list: D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D012338:RNA, Ribosomal, 23S; D000069349:Linezolid