MONOTHERAPY FOR FEVER AND NEUTROPENIA IN CANCER-PATIENTS - A RANDOMIZED COMPARISON OF CEFTAZIDIME VERSUS IMIPENEM

Purpose: To compare the efficacy of ceftazidime and imipenem monothera py for fever and neutropenia, and to determine whether fewer antimicro bial modifications (additions or changes) are required by the broader- spectrum agent, imipenem. Patients and Methods: Adult and pediatric pa tients undergoing chemotherapy for solid tumors, leukemias, or lymphom as were randomized to receive open-label ceftazidime or imipenem on pr esentation with fever and neutropenia. Success with or without modific ations of the initial antibiotic was defined os survival through neutr openia; 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 document ed infections on either monotherapy. Antianaerobic agents were more fr equently added to ceftazidime (P < .001), but addition of other antibi otics, including vancomycin and aminoglycosides, was similar between t he two monotherapy groups. Imipenem therapy was associated with signif icantly greater toxicity, manifested by Clostridium difficile-associat ed diarrhea and by nausea and vomiting, which required discontinuation of imipenem in 10% of recipients. Conclusion: Ceftazidime and imipene m are both effective in the management of fever and chemotherapy-relat ed neutropenia, provided that modifications are mode in response to cl inical and microbiologic data that emerge during the course of neutrop enia. Imipenem, despite its broader antimicrobial spectrum, does not s ignificantly decrease the overall need for antibiotic modifications an d is more often complicated by gastrointestinal toxicity.