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Systematic Review of Piperacillin-Induced Neutropenia

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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 β-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.

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Acknowledgements

This review was supported in part from a grant from the National Cancer Institute 1R01CA 102713-01 (Dr Bennett) and P 30 CA60553 (Dr McKoy). The other authors received no funding for preparation or publication of this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

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Authors and Affiliations

  1. Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois, USA

    Marc H. Scheetz & Steve Trifilio

  2. Division of Geriatric Medicine, Midwest Center for Health Services Research and Policy Studies, VA Chicago Healthcare System, Chicago, Illinois, USA

    June M. McKoy

  3. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, Illinois, USA

    June M. McKoy

  4. Midwest Center for Health Services and Policy Research, Hines VA Hospital and Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA

    Jorge P. Parada

  5. Interdisciplinary Oncology Program, H. Lee Moffitt Cancer Center and Research Institute at the University of South Florida, Tampa, Florida, USA

    Benjamin Djulbegovic

  6. VA Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center, University of New Mexico, College of Pharmacy, Albuquerque, New Mexico, USA

    Dennis W. Raisch & Rita Jakiche

  7. Department of Emergency Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA

    Paul R. Yarnold &  Charles L. Bennett

  8. Division of Hematology/Oncology, Feinberg School of Mecicine; Northwestern University, MidWest Center for Health Services Research and Policy Studies, VA Chicago Healthcare System, - Lakeside Division, Suite 205, 400 E. Ontario Street, Chicago, Illinois, 60611, USA

    Jessica Zagory, Adam Kahn, Kevin Chandler &  Charles L. Bennett

  9. Division of Infectious Diseases, Feinberg School of Medicine, Northwestern University Medical School, Chicago, Illinois, USA

    Frank Palella

  10. Institute for Healthcare Studies, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

    Charles L. Bennett

Authors
  1. Marc H. Scheetz
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  2. June M. McKoy
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  3. Jorge P. Parada
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  4. Benjamin Djulbegovic
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  5. Dennis W. Raisch
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  6. Paul R. Yarnold
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  7. Jessica Zagory
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  8. Steve Trifilio
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  9. Rita Jakiche
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  10. Frank Palella
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  11. Adam Kahn
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  12. Kevin Chandler
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  13. Charles L. Bennett
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Corresponding author

Correspondence to Charles L. Bennett.

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Scheetz, M.H., McKoy, J.M., Parada, J.P. et al. Systematic Review of Piperacillin-Induced Neutropenia. Drug-Safety 30, 295–306 (2007). https://doi.org/10.2165/00002018-200730040-00002

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  • DOI: https://doi.org/10.2165/00002018-200730040-00002

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