The Clinical and Laboratory Standards Institute (CLSI) lowered the MIC breakpoints for
meropenem and
imipenem from 4 mg/liter to 1 mg/liter for Enterobacteriaceae in 2010. The breakpoint change improves the probability of pharmacodynamic target attainment and eliminates the need for microbiology labs to perform confirmatory testing for Klebsiella pneumoniae
carbapenemase (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 with Enterobacteriaceae with 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 with
Enterobacteriaceae infections treated with
meropenem,
imipenem, or
doripenem. Patients with
Enterobacteriaceae infection 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 with Enterobacteriaceae with 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.