Because
penicillin agents are implicated in granulopoiesis inhibition, healthcare professionals frequently consider discontinuation of such
therapy in patients with decreasing white blood cell counts. No systematic review to date has described
piperacillin and the patient population at risk for this
adverse drug reaction (ADR). This review sought to assess the occurrence of
piperacillin-induced
neutropenia, describe characteristics of affected patients and assess the reporting modalities that most accurately classify this ADR. Case reports, cohort studies and clinical trials identified by comprehensive searches of PubMed and the US FDA Adverse Event Reporting System (AERS) database were reviewed for patient demographics, duration and dose of
piperacillin or
piperacillin-tazobactam treatment and the occurrence of
neutropenia. Causality assessments were performed. Six published case reports, three cohort studies, 178 clinical trials and two compilations of phase I-III trials were reviewed. Review of case reports was notable in that the duration of
beta-lactam therapy prior to the noting of
leukopenia always exceeded 15 days. No deaths were recorded in this group. Among 13,816 patients enrolled in non-neutropenic
fever studies, the occurrence of
piperacillin-induced
neutropenia was rare: five patients (0.04%) developed
neutropenia; none died. The demographics for this group were poorly documented. Through the AERS database, we identified 366 unique cases of
piperacillin or
piperacillin-tazobactam-induced haematological abnormalities, including
neutropenia (n = 183, 50.0%),
leukopenia, (n = 99, 27%),
agranulocytosis (n = 58, 15.8%) and others. In 62 cases, patients received between 1 and 14 days of
therapy (mean 7.7 + 4.1 days). Overall, there were 82 (22.4%) deaths. Reports of haematological ADRs among patients receiving
piperacillin or
piperacillin-tazobactam are rare. Report of
neutropenia associated with
piperacillin usage prior to 15 days of
therapy is a novel finding that requires further evaluation. Current reporting methods poorly characterise patient groups at risk.