Piperacillin–tazobactam tolerability in patients with a labeled penicillin allergy (PIPPEN)

Background: Piperacillin–tazobactam is a beta-lactam antibiotic with a distinct R1 side chain compared to other penicillins, therefore the risk of cross-reactivity should be theoretically low. Despite this difference, antimicrobial guidelines recommend against using piperacillin–tazobactam in patients with penicillin allergies. There is limited data available regarding piperacillin–tazobactam use in patients with a penicillin allergy, or rates of cross-reactivity. Therefore, the objective of this study was to assess the incidence of cross-reactivity to piperacillin–tazobactam in patients with a labeled penicillin allergy. Methods: This was a retrospective study of patients admitted to Surrey Memorial Hospital (SMH) between November 1 st , 2021 to January 31 st , 2024 assessing tolerance to piperacillin–tazobactam in patients with prior labeled penicillin allergies. Baseline characteristics and outcomes were collected from electronic medical records (EMR). Results: Of the 191 patients included, 98% were found to tolerate one or more doses of piperacillin–tazobactam. This included 95 patients with “low risk delayed reactions,” 90 patients with “high risk anaphylactic reactions,” and 2 patients with “well-documented delayed reactions,” to penicillins. Only four patients out of 191 had documented intolerance to piperacillin-tazobactam post-exposure. Conclusion: This study suggests that piperacillin–tazobactam has a low risk of intolerability (2%) in patients with labeled penicillin allergies, and that it is reasonable to consider piperacillin–tazobactam as an alternative to carbapenems and other broad-spectrum antibiotics for most patients with a previous penicillin allergy.