Piperacillin-Tazobactam Hypersensitivity: A Large, Multicenter Analysis

BACKGROUND: Piperacillin/tazobactam is a broad-spectrum penicillin. Hypersensitivity reactions are less commonly reported than with other penicillins except in patients with cystic fibrosis. OBJECTIVE: Detailed clinical characterization of a patient cohort referred with suspected piperacillin-tazobactam hypersensitivity. METHODS: Retrospective analysis of the demographic characteristics, clinical presentation, investigation, and management of 87 patients presenting to 5 European allergy centers. Patients underwent skin prick and intradermal testing with piperacillin/tazobactam, major (penicilloyl-polylysine) and minor (sodium penilloate) determinants, amoxicillin, benzylpenicillin, flucloxacillin, co-amoxiclav, clavulanic acid, and meropenem with immediate and, where appropriate, delayed reading of tests. Skin test -negative patients underwent drug provocation to piperacillin/tazobactam and/or other penicillins. A multistep protocol was used, depending on risk assessment. RESULTS: Forty-eight of 87 (55%) patients were diagnosed with hypersensitivity to piperacillin/tazobactam with either positive & nbsp;skin or drug provocation test results, of whom 10 (21%) had a diagnosis of cystic fibrosis. Twenty-six (54%) patients presented with immediate and 22 (45%) with nonimmediate hypersensitivity. Patients with cystic fibrosis predominantly presented with nonimmediate hypersensitivity (70%). Reactions were severe in 52% of immediate reactors (Brown's anaphylaxis grade 3) and moderately severe (systemic involvement) in 75% of nonimmediate reactors. The number of patients with negative skin test results tolerating reintroduction was comparable in immediate (80%) and nonimmediate (88%) hypersensitivity. One-third of patients were cross-sensitized to other penicillins. The cross-sensitization pattern raised the possibility of tazobactam allergy in 3 patients. In 21 patients selectively sensitized to piperacillin/tazobactam (12 immediate, 9 nonimmediate), tolerance to other beta-lactams was demonstrated by drug provocation testing. CONCLUSIONS: Piperacillin-tazobactam caused immediate and nonimmediate hypersensitivity with similar frequency. Most patients were selectively sensitized and tolerated other penicillins. Some patients may be allergic to the beta-lactamase inhibitor only. (C) 2021 American Academy of Allergy, Asthma & Immunology

Automated summary

The study found that hypersensitivity reactions caused by piperacillin/tazobactam are more common in patients with cystic fibrosis. Patients with negative skin test results but having allergies still tolerated reintroduction of the drug, and most patients exhibited selectively sensitized and tolerated other penicillins.