Antibiotic tolerance and persistence in clinical isolates of Escherichia coli evaluated by high-resolution time-kill assays

Abstract

Studies of the clinical impact of antibiotic tolerance and persistence have lacked standardized protocols and definitions. This study uses reference methodology and mathematical modeling to provide quantitative measures in clinical E. coli isolates of metrics commonly used to describe tolerance and persister cell frequency. We observe that the β-lactam-mediated killing is preceded by a bacteriostatic phase that was absent for ciprofloxacin. The data indicate that tolerance may be specific for the mechanism of antibiotic action, and persister cell frequency varies for different drug classes. Using the data obtained from the study isolates, we do not observe increased tolerance for any isolate for the antibiotics tested, and only a single isolate displayed a high persistence phenotype. This study provides a basis for obtaining quantitative definitions of isolates showing high degrees of tolerance and/or persistence.