Efficacy of telavancin alone & in combination with Ampicillin in a rat model of enterococcus faecalis endocarditis

Truc T. Tran, Vincent H. Tam, Barbara E. Murray, Cesar A. Arias, Kavindra Singh

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 μg/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.

Original languageEnglish (US)
Article numbere02489-16
JournalAntimicrobial Agents and Chemotherapy
Volume61
Issue number6
DOIs
StatePublished - Jun 2017

Keywords

  • Enterococcus faecalis
  • Rat endocarditis
  • Telavancin
  • Therapy

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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