Systematic review of piperacillin-induced neutropenia
Marc H Scheetz1, June M McKoy, Jorge P Parada
1Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Il 60611, USA.
Abstract:
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.
Insights
Healthcare professionals should be aware of piperacillin-induced neutropenia, a rare adverse drug reaction. This review highlights that neutropenia can occur earlier than 15 days of piperacillin therapy, necessitating further investigation into at-risk patient populations.
Area of Science:
- Pharmacology and Toxicology
- Hematology
Background:
- Penicillin agents, including piperacillin, can inhibit granulopoiesis, leading to decreased white blood cell counts.
- Healthcare providers often consider discontinuing penicillin therapy when neutropenia is observed.
- There is a lack of systematic reviews detailing piperacillin-induced neutropenia and at-risk patient demographics.
Purpose of the Study:
- To assess the incidence of piperacillin-induced neutropenia.
- To describe the characteristics of patients affected by this adverse drug reaction.
- To evaluate reporting modalities for classifying piperacillin-induced neutropenia.
Main Methods:
- A comprehensive literature search was conducted on PubMed and the US FDA Adverse Event Reporting System (AERS) database.
- Included were case reports, cohort studies, and clinical trials.
- Data extracted included patient demographics, treatment duration and dose, and occurrence of neutropenia, with causality assessments performed.
Main Results:
- Review of case reports indicated leukopenia occurred after more than 15 days of beta-lactam therapy, with no deaths.
- In non-neutropenic fever studies (13,816 patients), piperacillin-induced neutropenia was rare (0.04%), with no fatalities.
- The AERS database identified 366 cases of hematological abnormalities; 183 (50%) were neutropenia, with 22.4% mortality. Notably, 62 cases involved therapy of 1-14 days.
Conclusions:
- Hematological adverse drug reactions associated with piperacillin or piperacillin-tazobactam are infrequent.
- The occurrence of neutropenia within 14 days of piperacillin therapy is a new finding requiring further research.
- Current reporting systems inadequately define patient groups susceptible to piperacillin-induced neutropenia.
Related Concept Videos
01:28Acute Pyelonephritis II: Diagnostic Studies and Management
01:27Acute Pyelonephritis I: Introduction