Association between piperacillin/tazobactam MIC and survival among hospitalized patients with Enterobacterales infections: retrospective cohort analysis of electronic health records from 161 US hospitals

Introduction A recent randomized trial has suggested an increased risk of mortality for ceftriaxone-non-susceptible Enterobacterales infections treated with piperacillin/tazobactam compared with meropenem despite MICs within the susceptible range. Methods We conducted a retrospective cohort study of clinical encounters within the Cerner Health Facts database to identify all encounters between 2001 and 2017 in which Enterobacterales infections were treated empirically with piperacillin/tazobactam and for which MICs to the drug were available. Multivariate regression analysis was performed to enable partitioning of MICs into discrete strata based on statistically significant difference in mortality risk. Results During the study period, 10 101 inpatient encounters were identified meeting inclusion criteria. The crude in-hospital mortality for the entire cohort was 16.5%. Partitioning analysis identified a breakpoint of <= 16/4 mg/L that dichotomized encounters into lower versus higher mortality risk strata in the primary cohort of overall infections. This finding persisted in sequentially granular subsets where specific MICs <= 8/4 mg/L were reported (in lieu of ranges) as well as in the high-reliability subset with bloodstream infections. A higher clinical breakpoint of >= 128/4 mg/L dichotomized encounters with respiratory tract infection. No breakpoint was identified when restricting to encounters with urinary tract infections, ICU admits or upon restricting analysis to encounters with ceftriaxone-resistant isolates. Conclusions Clinical data suggest improved outcomes when piperacillin/tazobactam is prescribed for Enterobacterales infections with an MIC of <= 16/4 mg/L compared with >= 32/4 mg/L.