Antagonism between Bacteriostatic and Bactericidal Antibiotics Is Prevalent

• DOI: 10.1128/aac.02463-14
• Publication Date: 2014-05-28T07:08:08Z
• Authors: Paolo S. Ocampo; Viktória Lázár; Balázs Papp; Markus Arnoldini; Pia Abel zur Wiesch; Róbert Busa-Fekete; Gergely Fekete; Csaba Pál; Martin Ackermann; Sebastian Bonhoeffer
• Keywords: 0301 basic medicine; Antibiotics, Antineoplastic; Microbial Sensitivity Tests; Microfluidic Analytical Techniques; Cytostatic Agents; Time-Lapse Imaging; Anti-Bacterial Agents; High-Throughput Screening Assays; 3. Good health; 03 medical and health sciences; Escherichia coli; Single-Cell Analysis; Drug Antagonism

Combination therapy is rarely used to counter the evolution of resistance in bacterial infections. Expansion use combination requires knowledge how drugs interact at inhibitory concentrations. More than 50 years ago, it was noted that, if bactericidal are most potent with actively dividing cells, then inhibition growth induced by a bacteriostatic drug should result an overall reduction efficacy when drug. Our goal here investigate this hypothesis systematically. We first constructed time-kill curves using five different antibiotics clinically relevant concentrations, and we observed antagonism between drugs. extended our investigation performing screen pairwise combinations 21 subinhibitory found that strong antagonistic interactions were enriched significantly among Finally, since relies on phenotypic effects produced classes, recreated these experiments microfluidic device performed time-lapse microscopy directly observe quantify division individual cells controlled antibiotic While single-cell observations supported drugs, they revealed unexpected variety cellular responses combinations, suggesting multiple mechanisms underlie interactions.