JAC Advance Access published online on May 29, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg277
© 2003 by The British Society for Antimicrobial Chemotherapy
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Original article
1 Division of Infectious Diseases, Geneva University Hospital,
CH-1211 Geneva 14, Switzerland
Received 8 January 2003
; revised 4 March 2003
; accepted 6 April 2003
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.
Keywords: Gram-positive bacteria, chronic infections,
antimicrobial agents
Comparative efficacy of daptomycin and vancomycin
in the therapy of experimental foreign body infection due to Staphylococcus
aureus
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