Journal Article

Comparison of in vitro static and dynamic assays to evaluate the efficacy of an antimicrobial drug combination against Staphylococcus aureus

Innovations Thérapeutiques et Résistances (InTheRes) ; Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT), Broussou, Diane, Toutain, Pierre-Louis, Bousquet‐mélou, Alain, Woehrlé, Frédérique, El Garch, Farid, Ferran, Aude, Royal Veterinary College - Department of Veterinary Basics Sciences, Vetoquinol SA

2019

Overview

An easily implementable strategy to reduce treatment failures in severe bacterial infections is to combine already available antibiotics. However, most in vitro combination assays are performed by exposing standard bacterial inocula to constant concentrations of antibiotics over less than 24h, which can be poorly representative of clinical situations. The aim of this study was to assess the ability of static and dynamic in vitro Time-Kill Studies (TKS) to identify the potential benefits of an antibiotic combination (here, amikacin and vancomycin) on two different inoculum sizes of two S. aureus strains. In the static TKS (sTKS), performed by exposing both strains over 24h to constant antibiotic concentrations, the activity of the two drugs combined was not significantly different the better drug used alone. However, the dynamic TKS (dTKS) performed over 5 days by exposing one strain to fluctuating concentrations representative of those observed in patients showed that, with the large inoculum, the activities of the drugs, used alone or in combination, significantly differed over time. Vancomycin did not kill bacteria, amikacin led to bacterial regrowth whereas the combination progressively decreased the bacterial load. Thus, dTKS revealed an enhanced effect of the combination on a large inoculum not observed in sTKS. The discrepancy between the sTKS and dTKS results highlights that the assessment of the efficacy of a combination for severe infections associated with a high bacterial load could be demanding. These situations probably require the implementation of dynamic assays over the entire expected treatment duration rather than the sole static assays performed with steady drug concentrations over 24h.

• Publisher: CCSD,Public Library of Science,Public Library of Science (PLoS)
• Subject: Amikacin / Amikacin - pharmacology / Anti-Bacterial Agents - pharmacology / Anti-infective agents / Antibiotics / Antimicrobial agents / Assaying / Bacteria / Bacterial diseases / Bacterial infections / Bacterial Load - drug effects / Biofilms - drug effects / Biology and Life Sciences / Combination drug therapy / Drug Combinations / Drug therapy / Drug Therapy, Combination / Drugs / Endocarditis / Exposure / Health aspects / Infections / Inoculum / Life Sciences / Medicine and Health Sciences / Methicillin-Resistant Staphylococcus aureus - drug effects / Microbial Sensitivity Tests / Regrowth / Staphylococcal infections / Staphylococcus aureus - drug effects / Staphylococcus infections / Strains (organisms) / Time Factors / Treatment outcome / Tuberculosis / Vancomycin / Vancomycin - pharmacology / Variation
• ISBN: 0004564428000