Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant < i > Enterococcus faecium < /i >

by Clare L. Kinnear, Elsa Hansen, Valerie J. Morley, Kevin C. Tracy, Meghan Forstchen, Andrew F. Read, Robert J. Woods The antimicrobial resistance crisis has persisted despite broad attempts at intervention. It has been proposed that an important driver of resistance is selection imposed on bacterial populations that are not the intended target of antimicrobial therapy. But to date, there has been limited quantit ative measure of the mean and variance of resistance following antibiotic exposure. Here we focus on the important nosocomial pathogenEnterococcus faecium in a hospital system where resistance to daptomycin is evolving despite standard interventions. We hypothesized that the intravenous use of daptomycin generates off-target selection for resistance in transmissible gastrointestinal (carriage) populations ofE.faecium. We performed a cohort study in which the daptomycin resistance ofE.faecium isolated from rectal swabs from daptomycin-exposed patients was compared to a control group of patients exposed to linezolid, a drug with similar indications. In the daptomycin-exposed group, daptomycin resistance ofE.faecium from the off-target population was on average 50% higher than resistance in the control group (n = 428 clones from 22 patients). There was also greater phenotypic diversity in daptomycin resistance within daptomycin-exposed patients. In patients where multiple samples over time were available, a wide variability in temporal dynamics were observed, from lon...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research