title: Effect of quinupristin/dalfopristin on the outcome of vancomycin-resistant Enterococcus faecium bacteraemia: comparison with a control cohort.
abstract: Serious infection with vancomycin-resistant Enterococcus faecium (VREF) strains has no proven effective antimicrobial therapy. We compared the clinical and bacteriological outcomes of 20 patients with VREF bacteraemia treated with quinupristin/dalfopristin (RP 59500), an investigational streptogramin, with a historical cohort of 42 patients with VREF bacteraemia treated with other agents. Quinupristin/dalfopristin demonstrated in-vitro bacteriostatic activity against all 20 initial VREF blood isolates (MIC range 0.03-0.50 mg/L) by macrobroth dilution. The clinical characteristics of both groups were comparable for major outcome-dependent variables. There were five cases of recurrent VREF bacteraemia in the quinupristin/dalfopristin-treated cohort and 21 in the controls (P = 0.11); persistence of VREF at the primary site was found in six and 18 of the evaluable patients with follow-up cultures in these two cohorts (P = 0.06). In-hospital mortality was high in both groups: 65% in the quinupristin/dalfopristin group and 52% in the control group; however, VREF-associated mortality was significantly lower in the quinupristin/dalfopristin group (five and 17 respectively; P = 0.05). Follow-up susceptibility testing of five VREF isolates in the quinupristin/ dalfopristin group did not demonstrate resistance to quinupristin/dalfopristin. Quinupristin/ dalfopristin may be a useful agent for the therapy of serious VREF infection. Further clinical investigations are warranted to confirm or refute its clinical efficacy.
authors.affiliation: Department of Medicine, University of Pittsburgh Medical Center, PA, USA.
authors.forename: P K
authors.initials: PK
authors.lastname: Linden
authors.forename: A W
authors.initials: AW
authors.lastname: Pasculle
authors.forename: D
authors.initials: D
authors.lastname: McDevitt
authors.forename: D J
authors.initials: DJ
authors.lastname: Kramer
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy* / Q000382:microbiology / Q000601:surgery; D015331:Cohort Studies; D004352:Drug Resistance, Microbial; D016984:Enterococcus faecium / Q000187:drug effects*; D005260:Female; D005500:Follow-Up Studies; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome; D014640:Vancomycin / Q000494:pharmacology*; D014769:Virginiamycin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000900:Anti-Bacterial Agents; D014769:Virginiamycin; C062940:quinupristin-dalfopristin; D014640:Vancomycin