title: High prevalence of isolates with reduced glycopeptide susceptibility in persistent or recurrent bloodstream infections due to methicillin-resistant Staphylococcus aureus.
abstract: Reduced susceptibility to glycopeptides in methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates is considered a risk factor for failure of glycopeptide therapy. We compared the prevalences of MRSA isolates with reduced glycopeptide susceptibility in patients with versus without persistent or recurrent MRSA bloodstream infections. A retrospective cohort study at the University Hospital of Geneva identified 27 patients with persistent or recurrent clonally related MRSA bacteremic episodes over an 8-year period, which included 208 consecutive nosocomial MRSA bacteremic episodes. Vancomycin and teicoplanin MICs were determined by a modified macrodilution assay allowing improved detection of glycopeptide-intermediate MRSA isolates (GISA), characterized by elevated teicoplanin or/and vancomycin MICs (≥ 4 μg/ml). For 16 patients (59%), their pretherapy and/or posttherapy MRSA isolates showed elevated teicoplanin MICs, among which 10 (37%) concomitantly displayed elevated vancomycin MICs. In contrast, 11 other patients (41%) were persistently or recurrently infected with non-GISA isolates. In comparison, only 39 (22%) of 181 single isolates from patients with no microbiological evidence of persistent or recurrent infections showed elevated teicoplanin MICs, among which 14 (8%) concomitantly displayed elevated vancomycin MICs. Clinical, microbiological, and pharmacokinetic variables for patients persistently or recurrently infected with GISA or non-GISA isolates were similar. Bacteremic patients with a poor response to glycopeptide therapy had a 2.8-fold- and 4.8-fold-higher rates of MRSA isolates displaying elevated teicoplanin and vancomycin MICs, respectively, than patients with single isolates (P < 0.0001). Detection of elevated teicoplanin MICs may help to predict a poor response to glycopeptide therapy in MRSA bacteremic patients.
authors.affiliation: Service of Infectious Diseases, Infection Control Program, Geneva University Hospital and Medical School, Geneva, Switzerland.
authors.forename: Ilker
authors.initials: I
authors.lastname: Uçkay
authors.forename: Louis
authors.initials: L
authors.lastname: Bernard
authors.forename: Marta
authors.initials: M
authors.lastname: Buzzi
authors.forename: Stephan
authors.initials: S
authors.lastname: Harbarth
authors.forename: Patrice
authors.initials: P
authors.lastname: François
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Huggler
authors.forename: Tristan
authors.initials: T
authors.lastname: Ferry
authors.forename: Jacques
authors.initials: J
authors.lastname: Schrenzel
authors.forename: Adriana
authors.initials: A
authors.lastname: Renzoni
authors.forename: Pierre
authors.initials: P
authors.lastname: Vaudaux
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Lew
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology*; D002675:Child, Preschool; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D012008:Recurrence; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D017334:Teicoplanin / Q000494:pharmacology* / Q000627:therapeutic use; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin; D014640:Vancomycin