Efficacy of telavancin alone and in Combination with ampicillin in a rat model of enterococcus faecalis endocarditis
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Antimicrobial Agents and Chemotherapy, 1098-6596, Vol. 61, Nro. 6, 2017, p. 1-9
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American Society for Microbiology
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Abstract
We first assessed telavancin (TLV) pharmacokinetics in rats after a single
subcutaneous dose of 35 mg/kg of body weight. The pharmacokinetic data were
used to predict a TLV dose that simulates human exposure, and the efficacy of TLV
was then evaluated using a TLV dose of 21 mg/kg every 12 h against Enterococcus
faecalis OG1RF (TLV MIC of 0.06 g/ml) in a rat endocarditis model with an indwelling catheter. Therapy was given for 3 days with TLV, daptomycin (DAP), or ampicillin
(AMP) monotherapy and with combinations of TLV plus AMP, AMP plus gentamicin
(GEN), and AMP plus ceftriaxone (CRO); rats were sacrificed 24 h after the last dose.
Antibiotics were given to simulate clinically relevant concentrations or as used in
other studies. TLV treatment resulted in a significant decrease in bacterial burden
(CFU per gram) in vegetations from 6.0 log10 at time 0 to 3.1 log10 after 3 days of
therapy. Bacterial burdens in vegetations were also significantly lower in the TLVtreated rats than in the AMP (P 0.0009)- and AMP-plus-GEN (P 0.035)-treated
rats but were not significantly different from that of the AMP-plus-CRO-treated rats.
Bacterial burdens from vegetations in TLV monotherapy and TLV-plus-AMP-and-DAP
groups were similar to each other (P 0.05). Our data suggest that further study of
TLV as a therapeutic alternative for deep-seated infections caused by vancomycinsusceptible E. faecalis is warranted.
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Telavancin, Enterococcus faecalis, Therapy, Rat endocarditis