Impact of Penicillin Allergy on Empirical Carbapenem Use in Gram-Negative Bloodstream Infections: An Antimicrobial Stewardship Opportunity

Abstract

Objectives: Retrospective matched-cohort study evaluating association between penicillin allergy and empirical carbapenem use in gram-negative bloodstream infections (BSIs) and utility of antimicrobial stewardship interventions in reducing carbapenem utilization.

Methods: Hospitalized adults with community-onset gram-negative BSI from January 1, 2010, to June 30, 2015, at two large community hospitals in Columbia, SC, were identified. Antimicrobial stewardship interventions targeting penicillin allergy and carbapenem utilization were fully implemented January 1, 2014. Multivariate logistic regression was used to examine impact of penicillin allergy and antimicrobial stewardship interventions on empirical carbapenem use. Kaplan-Meier analysis was used to evaluate time to carbapenem deescalation in patients with penicillin allergy before and after interventions.

Results: Patients with penicillin allergy (n=140) were more likely to receive empirical carbapenem therapy for community-onset gram-negative BSI compared to those without penicillin allergy (n=140) (27% vs 12%, p=0.002). After adjustments in the multivariate model, penicillin allergy (odds ratio [OR] 3.98, 95% confidence interval [CI] 1.98-8.45) and prior β-lactam use (OR 2.72, 95% CI 1.07-6.64) were independently associated with empirical carbapenem use, whereas antimicrobial stewardship interventions were associated with decline in carbapenem utilization (OR 0.41, 95% CI 0.16-0.94). Among patients with penicillin allergy who were prescribed empirical carbapenems, median time to carbapenem deescalation was significantly shorter in the postintervention versus preintervention period (2.0 vs 4.2 days, p=0.004).

Conclusion: Penicillin allergy was a significant contributor to carbapenem use in community-onset gram-negative BSI. This was subject to modification by antimicrobial stewardship interventions, which successfully reduced overall carbapenem use and duration of carbapenem therapy in patients with penicillin allergy.

Keywords: bacteremia; cephalosporins; cross-reactivity; ertapenem; meropenem; β-lactams.