Efficacy of Telavancin Alone and in Combination with Ampicillin in a Rat Model of Enterococcus faecalis Endocarditis

Author:

Tran Truc T.12,Tam Vincent H.32,Murray Barbara E.142,Arias Cesar A.1425,Singh Kavindra V.12

Affiliation:

1. Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA

2. UTHealth Center for Antimicrobial Resistance and Microbial Genomics, Houston, Texas, USA

3. College of Pharmacy, University of Houston, Houston, Texas, USA

4. Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas, USA

5. Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia

Abstract

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 log 10 at time 0 to 3.1 log 10 after 3 days of therapy. Bacterial burdens in vegetations were also significantly lower in the TLV-treated 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 vancomycin-susceptible E. faecalis is warranted.

Funder

Theravance Biopharma Antibiotics Inc

Theravance Biopharma Antibiotics, Inc.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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