Risk Factors and Outcomes Associated With Acquisition of Daptomycin and Linezolid–Nonsusceptible Vancomycin-Resistant Enterococcus

Abstract

BackgroundVancomycin-resistant enterococcus (VRE) causes substantial health care–associated infection with increasing reports of resistance to daptomycin or linezolid. We conducted a case–control study reporting 81 cases of daptomycin and linezolid–nonsusceptible VRE (DLVRE), a resistance pattern not previously reported.MethodsWe reviewed VRE isolates from June 2010 through June 2015 for nonsusceptibility to both daptomycin (minimum inhibitory concentration [MIC] > 4) and linezolid (MIC ≥ 4). We matched cases by year to control patients with VRE susceptible to both daptomycin and linezolid and performed retrospective chart review to gather risk factor and outcome data.ResultsWe identified 81 DLVRE cases. Resistance to both daptomycin and linezolid was more common than resistance to either agent individually. Compared with susceptible VRE, DLVRE was more likely to present as bacteremia without focus (P < 0.01), with DLVRE patients more likely to be immune suppressed (P = .04), to be neutropenic (P = .03), or to have had an invasive procedure in the prior 30 days (P = .04). Any antibiotic exposure over the prior 30 days conferred a 4-fold increased risk for DLVRE (odds ratio [OR], 4.25; 95% confidence interval [CI], 1.43−12.63; P = .01); multivariate analysis implicated daptomycin days of therapy (DOT) over the past year as a specific risk factor (OR, 1.10; 95% CI, 1.01−1.19; P = .03). DLVRE cases had longer hospitalizations (P = .04) but no increased risk for in-hospital death.ConclusionsDLVRE is an emerging multidrug-resistant pathogen associated with immune suppression, neutropenia, and recent invasive procedure. Prior antibiotic exposure, specifically daptomycin exposure, confers risk for acquisition of DLVRE.

Daptomycin treatment impacts resistance in off-target populations of vancomycin-resistant Enterococcus faecium

“…Daptomycin resistance has been shown to arise within patients during treatment [19]. Additionally, a number of studies have reported prior daptomycin treatment as a key risk factor for infection with daptomycinresistant VR E. faecium [20][21][22], which is consistent with off-target selection. Finally, transmission of VR E. faecium is common in hospital settings, meaning resistance that arises in one patient may pose a threat to others.…”

Impact of an Antimicrobial Stewardship Intervention on Within- and Between-Patient Daptomycin Resistance Evolution in Vancomycin-Resistant Enterococcus faecium

“…Third, hitchhiking is also a possibility, where daptomycin resistance alleles could be carried to high frequency either due to stochastic dynamics or because they happen to be present in a clone that for unrelated reasons had a fitness advantage in the hospital setting (33). While there are no known overlaps in resistance mutations between linezolid and daptomycin (34,35), coresistance is common in some settings (36). Thus, the increased linezolid use could drive daptomycin resistance; however, an increase in linezolid resistance was not observed in this time period.…”

Antimicrobial treatment impacts resistance in off-target populations of a nosocomial bacterial pathogen: a case-control study

“…Daptomycin resistance has been shown to arise within patients during treatment [19]. Additionally, a number of studies have reported prior daptomycin treatment as a key risk factor for infection with daptomycin resistant VRE [20][21][22], which is consistent with offtarget selection. Finally, transmission of VR E. faecium is common in hospital settings, meaning resistance that arises in one patient may pose a threat to others.…”