Clinical Outcomes of Enterobacteriaceae Infections Stratified by Carbapenem MICs

Abstract

The Clinical and Laboratory Standards Institute (CLSI) lowered the MIC breakpoints for meropenem and imipenem from 4 mg/liter to 1 mg/liter forEnterobacteriaceaein 2010. The breakpoint change improves the probability of pharmacodynamic target attainment and eliminates the need for microbiology labs to perform confirmatory testing forKlebsiella pneumoniaecarbapenemase (KPC) production or other beta-lactamases that hydrolyze carbapenems. However, there are limited data evaluating clinical outcomes of the affected breakpoints, and it is unknown if patients infected withEnterobacteriaceaewith reduced susceptibility are more likely to have poor outcomes when treated with a carbapenem. We conducted a single-center retrospective matched-cohort analysis in adult patients withEnterobacteriaceaeinfections treated with meropenem, imipenem, or doripenem. Patients withEnterobacteriaceaeinfection with a carbapenem MIC of 2 to 8 mg/liter were matched based on pathogen, source of infection, comorbidities, and disease severity (1:1 ratio) to those with a carbapenem MIC of ≤1 mg/liter. A total of 36 patients were included in the study. The group with carbapenem MICs of 2 to 8 mg/liter had a significantly higher 30-day mortality than the group with carbapenem MICs of ≤1 mg/liter (38.9% compared to 5.6%,P= 0.04). Total hospital length of stay (LOS) and intensive care unit (ICU) LOS were longer in the group with MICs of 2 to 8 mg/liter than in the group with MICs of ≤1 mg/liter (57.6 days compared to 34.4 days [P= 0.06] and 56.6 days compared to 21.7 days [P< 0.01], respectively). Patients infected withEnterobacteriaceaewith a carbapenem MIC of 2, 4, or 8 mg/liter had higher mortality rates and longer ICU LOS than matched cohorts with carbapenem MICs of ≤1 mg/liter, which supports CLSI's recommendation to lower susceptibility breakpoints for carbapenems.