Randomized, double-blind comparison of once-weekly dalbavancin versus twice-daily
linezolid therapy for the treatment of complicated skin and skin structure
infections.
Author(s): Jauregui LE(1), Babazadeh S, Seltzer E, Goldberg L, Krievins D, Frederick M,
Krause D, Satilovs I, Endzinas Z, Breaux J, O'Riordan W.
Affiliation(s): Author information:
(1)St. Vincent Mercy Medical Center, Toledo, Ohio, USA.
Publication date & source: 2005, Clin Infect Dis. , 41(10):1407-15
BACKGROUND: Dalbavancin, a novel lipoglycopeptide with a pharmacokinetic profile
that allows weekly dosing, is active against gram-positive bacteria, including
methicillin-resistant Staphylococcus aureus (MRSA). The efficacy of dalbavancin
for treatment of skin and skin structure infections (SSSIs) was demonstrated in a
phase 2 study.
METHODS: In a phase 3 noninferiority study, patients with complicated SSSIs,
including infections known or suspected to involve MRSA, were randomized (ratio,
2 : 1) in a double-blind manner to receive dalbavancin (1000 mg given
intravenously on day 1 and 500 mg given intravenously on day 8) or linezolid (600
mg given intravenously or intravenously/orally every 12 h for 14 days). Efficacy
was assessed by determining clinical and microbiological responses at the end of
therapy and at the test-of-cure visit. Relapses were identified by additional
follow-up approximately 1 month later.
RESULTS: MRSA was identified in 51% of patients from whom a pathogen was isolated
at baseline. Dalbavancin and linezolid demonstrated comparable clinical efficacy
in the clinically evaluable population at the test-of-cure visit (88.9% and 91.2%
success, respectively). The rate of clinical success at the end of therapy was
>90% in both arms. Less than 1.0% of patients in either treatment arm experienced
relapse after the test-of-cure visit. Both treatments yielded successful
microbiological response in excess of 85% among microbiologically evaluable
patients at end of therapy and at the test-of-cure visit for all pathogens
combined, for all S. aureus strains, and for MRSA. Gastrointestinal symptoms were
among the most common adverse events in both arms. A higher proportion of
patients in the linezolid arm reported adverse events that were judged by the
investigator to be probably/possibly related to treatment (dalbavancin arm, 25.4%
of subjects; linezolid arm, 32.2% of subjects).
CONCLUSIONS: Two doses of dalbavancin (1000 mg given on day 1 followed by 500 mg
given on day 8) were as well tolerated and as effective as linezolid given twice
daily for 14 days for the treatment of patients with complicated SSSI, including
those infected with MRSA.
|