Comparative efficacy of daptomycin and vancomycin in the therapy of experimental foreign body infection due to Staphylococcus aureus.
The therapeutic activity of daptomycin was compared with that of vancomycin in a rat model of subcutaneously implanted tissue cages chronically infected with strain Rev1, a spontaneous methicillin-susceptible revertant of the methicillin-resistant Staphylococcus aureus strain MRGR3, showing equivalent virulence to its parent. The MIC and MBC of daptomycin (in Mueller-Hinton broth supplemented with 50 mg/L Ca2+) or vancomycin for strain Rev1 were 1-2 and 2-4 or 1 and 2 mg/L, respectively. In vitro elimination of strain Rev1 in the presence of 50% tissue cage fluid was more rapid with daptomycin 4 mg/L compared with vancomycin. After 2 weeks of infection, viable counts of strain Rev1 averaged 6.49 log10 cfu/mL of tissue cage fluid (n = 87). Intraperitoneal administration of daptomycin 30 mg/kg once daily, or vancomycin 50 mg/kg twice daily, produced antibiotic levels continuously above MBC. After 7 days of therapy with daptomycin or vancomycin, mean +/- S.E.M. counts of Rev1 decreased (P < 0.05) by 1.11 +/- 0.25 (n = 28) or 0.80 +/- 0.31 (n = 35) log10 cfu/mL, respectively, compared with cages of untreated animals, but were not significantly different from each other. In daptomycin-treated rats, three cages yielded subpopulations with reduced susceptibility to daptomycin. In conclusion, a low dose regimen of daptomycin was at least equivalent to vancomycin against chronic foreign body infections due to S. aureus. Drug dosage should be adapted to obtain inflammatory fluid levels of daptomycin minimizing emergence of resistant subpopulations.
Vaudaux
Pierre
P
Division of Infectious Diseases, Geneva University Hospital, CH-1211 Geneva 14, Switzerland. pierre.vaudaux@hcuge.ch
Francois
Patrice
P
Bisognano
Carmelo
C
Li
Dongmei
D
Lew
Daniel P
DP
Schrenzel
Jacques
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D017576:Daptomycin / Q000627:therapeutic use*; D015194:Diffusion Chambers, Culture; D005547:Foreign Bodies; D007700:Kinetics; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D051381:Rats; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects; D014640:Vancomycin / Q000627:therapeutic use*
D000900:Anti-Bacterial Agents; D014640:Vancomycin; D017576:Daptomycin