The aim of this study was to compare the rate of therapeutic failure and emergence of resistance in critically ill patients treated by third-generation cephalosporins (3GCs) or piperacillin-tazobactam (PTZ) for wild-type AmpC-producing Enterobacteriaceae pulmonary infections.
In a multicenter retrospective cohort study over a 4-year period, all patients treated for a pulmonary infection related to wild-type AmpC-producing Enterobacteriaceae who received documented antibiotic therapy with 3GCs or PTZ after less than 48 hours of empirical antibiotic therapy were eligible. The main outcome was the rate of therapeutic failure, defined by an impaired clinical response under treatment and/or a relapse of pulmonary infection related to the same pathogen. The secondary outcome was a secondary acquisition of derepressed cephalosporinase-producing Enterobacteriaceae.
Over the study period, 244 patients were included; 56 (23%) experienced therapeutic failure and 19 (8%) experienced secondary acquisition of resistance. In the non-adjusted cohort, the rate of therapeutic failure and emergence of resistance were significantly higher in the 3GCs group (32 vs. 18%, p = 0.011 and 13 vs. 5%, p = 0.035, respectively). In the propensity score-matched population, the 3GCs group was associated with higher rates of therapeutic failure (HR = 1.61 [1.27 – 2.07]). The secondary de-escalation to 3GCs after 48h of PTZ as a first-line antibiotic therapy was not associated with increased rate of emergence of resistance.
Our study confirms that third-generation cephalosporins should be avoided as first-line antibiotic therapy in wild-type AmpC-producing Enterobacteriaceae pulmonary infections.