Emergence of linezolid-resistant Staphylococcus aureus after prolonged treatment of cystic fibrosis patients in Cleveland, Ohio.
Linezolid (LZD)-resistant Staphylococcus aureus (LRSA) isolates were monitored from 2000 to 2009 in Cleveland, OH. LRSA first emerged in 2004 only in cystic fibrosis (CF) patients, with 11 LRSA-infected CF patients being identified by 2009. LRSA was isolated from 8 of 77 CF patients with S. aureus respiratory tract infection treated with LZD from 2000 to 2006. Analysis of clinical data showed that the 8 CF patients with LRSA received more LZD courses (18.8 versus 5.9; P = 0.001) for a longer duration (546.5 versus 211.9 days; P < 0.001) and had extended periods of exposure to LZD (83.1 versus 30.1 days/year; P < 0.001) than the 69 with LZD-susceptible isolates. Five LRSA isolates included in the clinical analysis (2000 to 2006) and three collected in 2009 were available for molecular studies. Genotyping by repetitive extrapalindromic PCR and pulsed-field gel electrophoresis revealed that seven of these eight LRSA strains from unique patients were genetically similar. By multilocus sequence typing, all LRSA isolates were included in clonal complex 5 (seven of sequence type 5 [ST5] and one of ST1788, a new single-locus variant of ST5). However, seven different variants were identified by spa typing. According to the Escherichia coli numbering system, seven LRSA isolates 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 peptidyltransferase 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.
Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Andrea
A
Endimiani
Martha
M
Blackford
Elliot C
EC
Dasenbrook
Michael D
MD
Reed
Saralee
S
Bajaksouszian
Andrea M
AM
Hujer
Susan D
SD
Rudin
Kristine M
KM
Hujer
Vincent
V
Perreten
Louis B
LB
Rice
Michael R
MR
Jacobs
Michael W
MW
Konstan
Robert A
RA
Bonomo
D000081:Acetamides / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000382:microbiology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D023303:Oxazolidinones / Q000627:therapeutic use*; D016133:Polymerase Chain Reaction; D000090822:Ribosomal Protein L3; D021241:Spectrometry, Mass, Electrospray Ionization; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D055815:Young Adult
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; C000716547:RPL3 protein, human; D000090822:Ribosomal Protein L3; D000069349:Linezolid
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