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Activity of daptomycin alone and in combination with rifampin and gentamicin against Staphylococcus aureus assessed by time-kill methodology.

ABSTRACT: The synergistic effects of daptomycin plus gentamicin or rifampin were tested against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between 0.25 and 8 microg/ml. Daptomycin sub-MICs combined with gentamicin concentrations lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin.

SUBMITTER: Credito K

PROVIDER: S-EPMC1855505 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

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Activity of daptomycin alone and in combination with rifampin and gentamicin against Staphylococcus aureus assessed by time-kill methodology.

Credito Kim K Lin Gengrong G Appelbaum Peter C PC

Antimicrobial agents and chemotherapy 20070112 4

The synergistic effects of daptomycin plus gentamicin or rifampin were tested against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between 0.25 and 8 microg/ml. Daptomycin sub-MICs combined with gentamicin concentrations lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin. ...[more]

PMID: 17220402

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Project description:The findings of clinical and in vitro research support the theory that infective endocarditis (IE)-causing bacteria form biofilms and that biofilms negatively affect treatment outcomes. The purpose of the present study was to quantify the biofilm formation of methicillin (meticillin)-resistant Staphylococcus aureus (MRSA) isolates obtained from patients with IE and to evaluate the in vitro activities of daptomycin and vancomycin alone and in combination with rifampin (rifampicin) or gentamicin while monitoring the isolates for the development of resistance. A high-inoculum, stationary-phase infection model of IE was used to simulate the pharmacokinetics in humans of daptomycin at 6 mg/kg of body weight/day, vancomycin at 1.25 g every 12 h (q12h) alone and in combination with rifampin at 300 mg every 8 h, and gentamicin at 1.3 mg/kg q12h. Two randomly selected clinical MRSA isolates were obtained from patients with IE; both MRSA isolates quantitatively produced biofilms. The time to bactericidal activity in the presence of daptomycin was isolate dependent but was achieved by 24 h for both MRSA isolates. Vancomycin did not achieve bactericidal activity throughout the experiment. At 24, 48, and 72 h, daptomycin-containing regimens had significantly more activity (greater declines in the mean number of CFU/g) than any of the vancomycin-containing regimens (P = 0.03). Rifampin and gentamicin antagonized or delayed the bactericidal activity of daptomycin (against MRSA B346846 for rifampin and against both isolates for gentamicin) in the first 24 h. Increases in the daptomycin and vancomycin MICs were not observed. We conclude that in an IE model of biofilm-forming MRSA, daptomycin monotherapy has better in vitro activity than daptomycin in combination with rifampin or gentamicin or any vancomycin-containing regimen studied within the first 24 h. Further investigations are needed to understand the initial delay in bactericidal activity observed when gentamicin or rifampin is combined with daptomycin.

Dataset Information

Activity of daptomycin alone and in combination with rifampin and gentamicin against Staphylococcus aureus assessed by time-kill methodology.

Publications

Activity of daptomycin alone and in combination with rifampin and gentamicin against Staphylococcus aureus assessed by time-kill methodology.

Similar Datasets

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