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.