Pharmacodynamics of Daptomycin against Enterococcus faecium and Enterococcus faecalis in the Murine Thigh Infection Model

Antimicrobial Agents and Chemotherapy
James M KiddDavid P Nicolau

Abstract

The Clinical and Laboratory Standards Institute (CLSI) daptomycin MIC susceptibility breakpoint for the treatment of enterococcal infections is ≤4 μg/ml. However, patients receiving daptomycin for the treatment of infections caused by enterococci with MICs of ≤4 μg/ml may experience treatment failures. We assessed the pharmacodynamics of daptomycin against enterococci in a neutropenic murine thigh infection model and determined the exposures necessary for bacteriostasis and a 1-log10-CFU reduction of Enterococcus faecalis and Enterococcus faecium We further characterized daptomycin efficacy at clinically achievable exposures. Six E. faecium and 6 E. faecalis isolates (daptomycin MICs, 0.5 to 32 μg/ml) were studied. Daptomycin was administered at various doses over 24 h to achieve area under the free drug concentration-time curve-to-MIC ratios (fAUC0-24/MIC) ranging from 1 to 148. Daptomycin regimens that simulate mean human exposures following doses of 6, 8, and 10 mg/kg of body weight/day were also studied. Efficacy was assessed by the differences in the number of log10 CFU per thigh at 24 h. The Hill equation was used to estimate the fAUC0-24/MIC required to achieve bacteriostasis and a 1-log10-CFU reduction. For E. faecium, ...Continue Reading

References

Feb 22, 2001·Antimicrobial Agents and Chemotherapy·A LouieG L Drusano
Jul 25, 2003·Antimicrobial Agents and Chemotherapy·Jared A SilvermanHoward M Shapiro
Dec 25, 2003·Antimicrobial Agents and Chemotherapy·Nasia SafdarW A Craig
Dec 5, 2006·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Paul G AmbroseGeorge L Drusano
Jul 9, 2009·The Annals of Pharmacotherapy·Pamela A MoiseKenneth C Lamp
Apr 7, 2010·The Journal of Antimicrobial Chemotherapy·Rafael CantónAlan P Johnson
Jun 19, 2013·Antimicrobial Agents and Chemotherapy·Anthony M CasapaoMichael J Rybak
Oct 5, 2013·Clinical Microbiology Reviews·Romney M HumphriesGeorge Sakoulas
May 20, 2015·Clinical Therapeutics·Pamela A MoiseMarcus J Zervos
Sep 17, 2015·Circulation·Larry M BaddourUNKNOWN American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular
Apr 6, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Bhavarth S ShuklaCesar A Arias
Dec 25, 2016·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Nicholas S BrittMolly E Steed
Mar 23, 2017·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Yu-Chung ChuangShan-Chwen Chang

❮ Previous
Next ❯

Citations

Sep 7, 2018·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Lindsay M AveryDavid P Nicolau
Apr 12, 2019·Journal of Clinical Microbiology·Romney M HumphriesJanet A Hindler
Nov 2, 2019·Journal of Clinical Microbiology·Lindsey E NielsenRomney Humphries
May 17, 2019·Journal of Clinical Microbiology·Romney M Humphries
Sep 11, 2019·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Michael J SatlinJames H Jorgensen
Feb 6, 2021·Pathogens·Gustavo Henrique Rodrigues Vale de MacedoLuís Cláudio Nascimento da Silva
May 1, 2020·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·J TurnidgeUNKNOWN European Committee on Antimicrobial Susceptibility Testing

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.