2396. Fosfomycin Resistance Among Carbapenem-Resistant Enterobacteriaceae Clinical Isolates in Connecticut, 2017

Abstract

BackgroundFosfomycin is among the limited treatment options for carbapenem-resistant Enterobacteriaceae (CRE) infections. Despite its use, prevalence of fosfomycin resistance among CRE in the United States is largely unknown. In 2017, submission of Enterobacteriaceae isolates resistant to ≥1 carbapenem became mandated in Connecticut (CT), allowing further characterization at the state public health laboratory (SPHL). We analyzed fosfomycin resistance among CRE isolates in CT during 2017, and explored demographic and molecular factors potentially associated with resistance.MethodsAfter confirming carbapenem resistance, SPHL tests fosfomycin susceptibility using disk diffusion. For each CRE patient, the isolate most resistant to fosfomycin was included in this analysis. We used the Clinical and Laboratory Standards Institute (CLSI) fosfomycin breakpoint for Escherichia coli (nonsusceptible <16 mm) to evaluate associations among fosfomycin resistance and demographic factors, carbapenemase activity (modified carbapenem inactivation method, mCIM) and carbapenemase genes tested at SPHL. We report fosfomycin resistance rate by European Committee on Antimicrobial Susceptibility Testing (EUCAST, resistance <24 mm for E. coli) criteria for comparison.ResultsAmong 138 CRE isolates, 39 (28.3%) were fosfomycin nonsusceptible by CLSI criteria. Most nonsusceptible isolates were Enterobacter cloacae (18; 46.2%) or Klebsiella pneumoniae (17; 43.6%). Isolates from patients aged ≥65 years were more likely to be fosfomycin nonsusceptible than isolates from patients aged <65 years (χ2 = 3.8; P = 0.050). No other demographic characteristics were statistically significant. Of fosfomycin nonsusceptible isolates, 12 (30.8%) produced a carbapenemase (mCIM-positive), and 9 (23.1%) had the blaKPC gene. By EUCAST criteria, 96 (69.6%) CRE isolates were fosfomycin resistant.ConclusionA substantial proportion of CRE in CT during 2017 were fosfomycin nonsusceptible, and nonsusceptibility was associated with older patient age. Fosfomycin resistance risk factors and molecular mechanisms need further exploration. The substantial proportion of isolates with results falling between CLSI and EUCAST breakpoints warrants evaluation.Disclosures All authors: No reported disclosures.