Imipenem/Cilastatin versus Cefepime as Empiric Monotherapy for Fever in Neutropenic Patients after ematopoietic Stem Cell Transplantation

Abstract

Objective: To evaluate the potential advantages of imipenem/cilastatin in control of fever in neutro-penic HSCT recipients.Patients and Method: In this single-center study, 111 consecutive febrile episodes in 104 neutropenic HSCT recipients with a mean age of 26 years were randomized to treatment either with Imipenem/cilastatin 1 g, IV, q8h or cefepime (our standard regimen) 2 g, IV, q8h. If fever persisted, se¬quential antibiotics were added in 72-hour intervals: vancomycin, amikacin and amphotericin-B. The study population was at serious risk of a poor outcome, since 73.5% of febrile episodes occurred after allogeneic and 26.5% of febrile events occurred after autologous hematopoietic stem cell transplanta¬tion.
Results: The median total duration of neutropenia was 10 days, and the median leukocyte count at study inclusion was 0.16 × 109/l. The two patient groups were comparable in terms of Age, gender, un¬derlying disease, conditioning regimen, clinical and bacterial documentation, severity and duration of neutropenia and mucositis, GI decontamination and G-CSF administration. Bacteremia was found in 20.6%, other microscopically documented infections in 9.8%, clinically documented infections in 20.6% and fever of unknown origin in 49% of the febrile episodes. Most (102) febrile episodes were evaluable for response. No significant difference was found between imipenem/cilastatin and cefepime in terms of success rate (73.1% versus 62%), empirical addition of vancomycin (38% versus 26.2%) or median duration of antibiotic therapy (7 days in both).The difference between imipenem/cilastatin and cefepime was statistically significant for median duration of fever (1.5 versus 2 days) and median time of resolution of neutropenia (12 versus 14 days). The overall response rates to initial monotherapy was significantly higher for HSCT recipients with thalassemia, MM, lymphoma, AA, than recipients with ALL, AML, CML, CLL (P<0.001) and for episodes of fever of unknown origin than episodes of clini¬cally documented infections (87.8% versus 12.2%). In episodes of success without modification, the median duration of neutropenia before entry was longer than episodes when vancomycin was added (P<0.027).No patient died from the infection. Both antibiotic regimens were well tolerated. The study treatment being stopped only in 1 patient because of toxicity (cutaneous allergy to imipenem/cilastatin).
Conclusions: Imipenem/cilastatin and cefepime are effective and well tolerated when used as initial empirical treatment for HSCT recipient with prolonged neutropenia. But imipenem/cilastatin may be more effective than cefepime, as evidenced by a significantly better response in two outcome measures and in one subgroup of patients (AML).