Monotherapy for fever and neutropenia in cancer patients: A randomized comparison of ceftazidime versus imipenem

Alison G. Freifeld, Thomas Walsh, Doris Marshall, Janet Gress, Seth M. Steinberg, James Hathorn, Marc Rubin, Paul Jarosinski, Vee Gill, Robert C. Young, Philip A. Pizzo

Research output: Contribution to journalArticlepeer-review

200 Scopus citations

Abstract

Purpose: To compare the efficacy of ceftazidime and imipenem monotherapy for fever and neutropenia, and to determine whether fewer antimicrobial modifications (additions or changes) are required by the broader-spectrum agent, imipenem. Patients and Methods: Adult and pediatric patients undergoing chemotherapy for solid tumors, leukemias, or lymphomas were randomized to receive open-label ceftazidime or imipenem on presentation with fever and neutropenia. Success with or without modifications of the initial antibiotic was defined as survival through neutropenia; failure was death due to infection. Comparisons were based on numbers of modifications made to each monotherapy during the course of neutropenia, in patients stratified as having unexplained fever or a documented infection. Results: Among 204 ceftazidime and 195 imipenem recipients, the overall success rate with or without modification was more than 98%, regardless of initial antibiotic regimen. Modifications occurred in half of all episodes, primarily in patients with documented infections on either monotherapy. Antianaerobic agents were more frequently added to ceftazidime (P < .001), but addition of other antibiotics, including vancomycin and aminoglycosides, was similar between the two monotherapy groups. Imipenem therapy was associated with significantly greater toxicity, manifested by Clostridium difficile- associated diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients. Conclusion: Ceftazidime and imipenem are both effective in the management of fever and chemotherapy- related neutropenia, provided that modifications are made in response to clinical and microbiologic data that emerge during the course of neutropenia. Imipenem, despite its broader antimicrobial spectrum, does not significantly decrease the overall need for antibiotic modifications and is more often complicated by gastrointestinal toxicity.

Original languageEnglish (US)
Pages (from-to)165-176
Number of pages12
JournalJournal of Clinical Oncology
Volume13
Issue number1
DOIs
StatePublished - Jan 1995
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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