Influence of Inoculum Effect on the Efficacy of Daptomycin Monotherapy and in Combination with β-Lactams against Daptomycin-Susceptible Enterococcus faecium Harboring LiaSR Substitutions.

Antimicrobial Agents and Chemotherapy
Razieh KebriaeiMichael J Rybak

Abstract

Enterococcus faecium isolates that harbor LiaFSR substitutions but are phenotypically susceptible to daptomycin (DAP) by current breakpoints are problematic, since predisposition to resistance may lead to therapeutic failure. Using a simulated endocardial vegetation (SEV) pharmacokinetic/pharmacodynamic (PK/PD) model, we investigated DAP regimens (6, 8, and 10 mg/kg of body weight/day) as monotherapy and in combination with ampicillin (AMP), ceftaroline (CPT), or ertapenem (ERT) against E. faecium HOU503, a DAP-susceptible strain that harbors common LiaS and LiaR substitutions found in clinical isolates (T120S and W73C, respectively). Of interest, the efficacy of DAP monotherapy, at any dose regimen, was dependent on the size of the inoculum. At an inoculum of ∼109 CFU/g, DAP doses of 6 to 8 mg/kg/day were not effective and led to significant regrowth with emergence of resistant derivatives. In contrast, at an inoculum of ∼107 CFU/g, marked reductions in bacterial counts were observed with DAP at 6 mg/kg/day, with no resistance. The inoculum effect was confirmed in a rat model using humanized DAP exposures. Combinations of DAP with AMP, CPT, or ERT demonstrated enhanced eradication and reduced potential for resistance, allowing...Continue Reading

References

Apr 24, 2003·Antimicrobial Agents and Chemotherapy·Raymond ChaMichael J Rybak
Dec 25, 2003·Antimicrobial Agents and Chemotherapy·Nasia SafdarW A Craig
Oct 13, 2006·The Journal of Antimicrobial Chemotherapy·Jacques VouillamozJosé M Entenza
Apr 2, 2008·Antimicrobial Agents and Chemotherapy·Nicole CotroneoJared A Silverman
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
Jun 24, 2010·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·C A AriasB E Murray
Feb 4, 2011·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Theodoros KelesidisDavid A Pegues
Apr 5, 2011·Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America·Mini KambojKent A Sepkowitz
Sep 9, 2011·The New England Journal of Medicine·Cesar A AriasGeorge M Weinstock
Mar 17, 2012·Nature Reviews. Microbiology·Cesar A Arias, Barbara E Murray
Nov 2, 2012·Antimicrobial Agents and Chemotherapy·Milya DavlievaYousif Shamoo
Mar 20, 2013·Antimicrobial Agents and Chemotherapy·Jose M MunitaCesar A Arias
May 22, 2013·Antimicrobial Agents and Chemotherapy·George SakoulasFadi Haddad
Sep 26, 2013·Antimicrobial Agents and Chemotherapy·Xavier HenryBernard Joris
Dec 25, 2013·Antimicrobial Agents and Chemotherapy·George SakoulasVictor Nizet
May 29, 2014·Antimicrobial Agents and Chemotherapy·Lorena DiazCesar A Arias
Aug 12, 2014·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jose M MunitaCesar A Arias
Sep 24, 2014·The Journal of Antimicrobial Chemotherapy·Katie E BarberMichael J Rybak
Sep 24, 2014·The Journal of Antimicrobial Chemotherapy·Jolanta PiszczekEric Partlow
Sep 16, 2015·Antimicrobial Agents and Chemotherapy·Diana PanessoCesar A Arias
May 14, 2016·World Journal of Virology·Muthannan Andavar Ramakrishnan
Oct 22, 2016·Infection Control and Hospital Epidemiology : the Official Journal of the Society of Hospital Epidemiologists of America·Lindsey M WeinerDawn M Sievert

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Citations

May 24, 2019·Current Infectious Disease Reports·German A ContrerasCesar A Arias
May 17, 2019·Journal of Clinical Microbiology·Romney M Humphries
Jun 24, 2020·Antimicrobial Agents and Chemotherapy·Taylor MorrisetteMichael J Rybak
Feb 5, 2021·The Annals of Pharmacotherapy·Timothy W JonesWilliam J Olney
Jul 6, 2021·Frontiers in Cell and Developmental Biology·Christian Johann LercheClaus Moser
Sep 29, 2021·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Franziska A SchwartzClaus Moser

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