Emergence of Linezolid-Resistant Staphylococcus aureus after prolonged treatment of Cystic Fibrosis Patients in Cleveland.
Antimicrob Agents Chemother. 2011 Jan 24;
Authors: Endimiani A, Blackford M, Dasenbrook EC, Reed MD, Bajaksouszian S, Hujer AM, Rudin SD, Hujer KM, Perreten V, Rice LB, Jacobs MR, Konstan MW, Bonomo RA
Linezolid (LZD) resistant Staphylococcus aureus (LRSA) isolates were monitored during 2000-2009 in Cleveland, Ohio. LRSA first emerged in 2004 only in cystic fibrosis (CF) patients, with 11 CF patients identified by 2009. LRSA were isolated from 8 of 77 CF patients with S. aureus respiratory tract infection treated with LZD during 2000-2006. Analysis of clinical data showed that the 8 CF patients with LRSA received more LZD courses (18.8 vs. 5.9; P=0.001) for a longer duration (546.5 vs. 211.9 days; P<0.001) and had extended periods of exposure (83.1 vs. 30.1 days/year; P<0.001) to LZD than the 69 with "LZD-susceptible isolates". Five LRSA isolates included in the clinical analysis (2000-2006) and three collected in 2009 were available for molecular studies. Genotyping by rep-PCR and PFGE revealed that 7 of these 8 LRSA strains from unique patients were genetically similar. By MLST, all LRSA isolates were included in CC5 (seven ST5 and one ST1788, a new single locus variant of ST5). However, 7 different variants were identified by spa typing. According to the Escherichia coli numbering system, 7 LRSA contained a G2576T mutation (G2603T S. aureus numbering) in one to four of the five copies of domain V of the 23S rRNA genes. One strain also contained a mutation (C2461T, E. coli numbering) not previously reported. Two strains, including one without domain V mutations, possessed single amino acid substitutions (Gly152Asp or Gly139Arg) in the ribosomal protein L3 of the peptidyl transferase center, substitutions not previously reported in clinical isolates. Emergence of LRSA is a serious concern for CF patients who undergo prolonged courses of LZD therapy.
PMID: 21263048 [PubMed - as supplied by publisher]