Efficacy of Telavancin Alone and in Combination with Ampicillin in a Rat Model of Enterococcus faecalis Endocarditis.
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 againstEnterococcus faecalisOG1RF (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 log10at time 0 to 3.1 log10after 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-susceptibleE. faecalisis warranted.
Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.|UTHealth Center for Antimicrobial Resistance and Microbial Genomics, Houston, Texas, USA.
Truc T
TT
Tran
College of Pharmacy, University of Houston, Houston, Texas, USA.|UTHealth Center for Antimicrobial Resistance and Microbial Genomics, Houston, Texas, USA.
Vincent H
VH
Tam
Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.|Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas, USA.|UTHealth Center for Antimicrobial Resistance and Microbial Genomics, Houston, Texas, USA.
Barbara E
BE
Murray
Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA.|Department of Microbiology and Molecular Genetics, University of Texas Medical School at Houston, Houston, Texas, USA.|UTHealth Center for Antimicrobial Resistance and Microbial Genomics, Houston, Texas, USA.|Molecular Genetics and Antimicrobial Resistance Unit, Universidad El Bosque, Bogota, Colombia.
Cesar A
CA
Arias
Division of Infectious Diseases, Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA kavindra.singh@uth.tmc.edu.|UTHealth Center for Antimicrobial Resistance and Microbial Genomics, Houston, Texas, USA.
Kavindra V
KV
Singh
D000617:Aminoglycosides / Q000627:therapeutic use*; D000667:Ampicillin; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002443:Ceftriaxone / Q000627:therapeutic use; D002511:Cephalosporins / Q000627:therapeutic use; D017576:Daptomycin / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004697:Endocarditis, Bacterial; D013293:Enterococcus faecalis; D005839:Gentamicins / Q000627:therapeutic use; D000077427:Lipoglycopeptides; D008297:Male; D008826:Microbial Sensitivity Tests; D051381:Rats; D017207:Rats, Sprague-Dawley; D014640:Vancomycin / Q000627:therapeutic use
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D005839:Gentamicins; D000077427:Lipoglycopeptides; D014640:Vancomycin; D002443:Ceftriaxone; D000667:Ampicillin; D017576:Daptomycin; C487637:telavancin
Enterococcus faecalis; rat endocarditis; telavancin; therapy