Outcomes of Patients with Amp-C Inducible Enterobacteriaceae infections Treated with Carbapenems versus Cefepime or Piperacillin-tazobactam

Background: Enterobacter spp., S. marcescens, C. freundii, Providencia spp., and M. morganii (ESCPM) contain a chromosomally located, inducible AmpC beta-lactamases, a unique mechanism of resistance. Carbapenems (CARB) and cefepime (CEF) are stable against inducible or constitutive AmpC expression. Piperacillin/tazobactam (PT) is not stable, but is not a strong AmpC inducer. Optimal therapy for these infections is unknown. We compared clinical outcomes between patients with ESCPM infections treated with CARB vs. CEF or PT.

Methods: Retrospective chart review of patients with ESCPM infections stratified by empiric CARB vs. CEF or PT. Patients had respiratory or blood cultures positive for beta-lactam susceptible ESPCM pathogens and were admitted to the hospital between January 1, 2012-January 1, 2015. The primary outcome was clinical failure. Secondary outcomes included 30-day readmission and mortality. Fisher’s exact test, 2-sided was used for statistical analysis, and significance was defined as a p-value <0.05.

Results: Analysis included 187 patients (CARB n=30 vs. CEF/PT n=157). The most common site of infection was respiratory (CARB 53.3% vs. CEF/PT 56.7%). At the start of antibiotics, severity of illness was similar: intensive care unit (ICU) admission (CARB 73.2% vs. CEF/PT 73.3%), receipt of mechanical ventilation (CARB 52.9% vs. CEF/PT 56.7%), and receipt of vasopressor agents (CARB 27.4%, CEF/PT 23.3%). All other baseline characteristics were similar between groups. The primary outcome of clinical failure in the CARB group was 13.3% vs. 26.8% in the CEF/PT, p=0.164. Rates of clinical failure for patients in the CARB group were lower in a subgroup of 137 ICU patients (CARB 9.1% vs. 29.6% (p=0.046). 30-day readmission was lower in the CARB group (8.7%) compared to CEF/PT (17.8%) but was not statistically significant (p=0.368) and 30-day morality was similar (CARB 24.8% vs. CEF/PT 23.3%, p=1.00).

Conclusion: Among 137 patients in ICU at start of empiric therapy, 2/22 (9.1%) of those treated with CARB had clinical failure, vs. 34/115 (29.6%) of patients treated with CEF/PT (P=0.03). A study with a larger sample size would be needed to determine if the trend is significant in the overall patient population.