Microbiologic characterization of isolates from a dalbavancin clinical trial for catheter-related bloodstream infections

Diagn Microbiol Infect Dis. 2006 Feb;54(2):83-7. doi: 10.1016/j.diagmicrobio.2005.09.004.

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.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacteremia / etiology
  • Bacteremia / microbiology*
  • Catheterization*
  • DNA, Bacterial / analysis
  • Electrophoresis, Gel, Pulsed-Field
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / genetics
  • Gram-Positive Bacteria / isolation & purification
  • Gram-Positive Bacterial Infections / etiology
  • Gram-Positive Bacterial Infections / microbiology*
  • Humans
  • Microbial Sensitivity Tests
  • Randomized Controlled Trials as Topic
  • Teicoplanin / analogs & derivatives*
  • Teicoplanin / chemistry
  • Teicoplanin / pharmacology
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Teicoplanin
  • Vancomycin
  • dalbavancin