title: Microbiologic characterization of isolates from a dalbavancin clinical trial for catheter-related bloodstream infections.
abstract: Dalbavancin, a new-generation semisynthetic lipoglycopeptide in phase 3 clinical development, has been documented to be more active than vancomycin or teicoplanin against Gram-positive bacteria, including multidrug-resistant strains, by in vitro testing and in animal models. The human pharmacokinetics of dalbavancin predicts efficacy at weekly dosing intervals. In a phase 2 open-label clinical trial, dalbavancin exhibited superiority when compared with vancomycin against catheter-related bloodstream infection (CR-BSI). The majority of pathogens identified in this study as in clinical practice were coagulase-negative staphylococci (CoNS), necessitating rigorous characterization of duplicate isolates to rule out contaminants and to validate cases for study evaluations. At follow-up for the intent-to-treat population, overall pathogen eradication was 92.3% for dalbavancin and 75.9% for vancomycin. We describe the details of organisms isolated, their epidemiologic/genetic characterization, susceptibility patterns against glycopeptides, and the eradication rates by organism group. In conclusion, dalbavancin was active against all isolated pathogens associated with CR-BSI (CoNS, Staphylococcus aureus and Enterococcus faecalis; all MIC results, < or = 0.25 microg/mL) and achieved significant (P < 0.05) clinical success when compared with vancomycin.
authors.affiliation: Vicuron Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: Beth P
authors.initials: BP
authors.lastname: Goldstein
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Fritsche
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Biedenbach
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D016470:Bacteremia / Q000209:etiology / Q000382:microbiology*; D002404:Catheterization; D004269:DNA, Bacterial / Q000032:analysis; D016521:Electrophoresis, Gel, Pulsed-Field; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000209:etiology / Q000382:microbiology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D016032:Randomized Controlled Trials as Topic; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D017334:Teicoplanin; D014640:Vancomycin; C469289:dalbavancin