title: Bactericidal activity and resistance development profiling of dalbavancin.
abstract: Dalbavancin, a semisynthetic lipoglycopeptide being developed for the treatment of skin and skin structure infections (SSSIs), has a half-life of 5 to 7 days in humans and offers promise for a convenient weekly dosing regimen. We studied the in vitro bactericidal activity of dalbavancin against target organisms, using the concentrations that are maintained in human blood with the proposed dosage regimen. Dalbavancin minimal bactericidal concentrations (MBCs) were<or=0.5 microg/ml for eight staphylococcal isolates; and for six of these strains, including one vancomycin-intermediate Staphylococcus aureus (VISA) isolate, the MBCs were equal to or within 1 doubling dilution of the MIC. Dalbavancin MICs for all three Streptococcus pyogenes strains were 0.008 microg/ml, as were the MBCs for two of the isolates. In time-kill studies conducted with a different set of seven strains (two methicillin-susceptible S. aureus isolates, three methicillin-resistant S. aureus isolates, one VISA isolate, and one S. pyogenes isolate), all strains exhibited a>or=3-log10 decrease in their viable counts when they were exposed to>or=1 microg/ml of dalbavancin for 24 h. Resistance development studies by both direct selection (resistance frequency, <10(-10)) and serial passage failed to produce stable mutants with decreased susceptibility to dalbavancin. These observations suggest that dalbavancin will be an effective choice for the management of patients with SSSIs.
authors.affiliation: Pfizer Inc., Pfizer Global Pharmaceuticals, King of Prussia, PA, USA.
authors.forename: Beth P
authors.initials: BP
authors.lastname: Goldstein
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Draghi
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sheehan
authors.forename: Patricia
authors.initials: P
authors.lastname: Hogan
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Sahm
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects*; D017334:Teicoplanin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014640:Vancomycin / Q000494:pharmacology; D020713:Vancomycin Resistance
chemical_list: D000900:Anti-Bacterial Agents; D017334:Teicoplanin; D014640:Vancomycin; C469289:dalbavancin; D017576:Daptomycin