PWSF1-6 - Comparison of Doripenem and Meropenem as the First-Line Mono-Therapy in Febrile Neutropenic Patients with Acute Leukemia

Abstract

Background: Febrile neutropenia (FN) are often observed in hematological malignancy (HEM) such as acute leukemia (AL). Carbapenem antibiotics having a potent and broad antibacterial activity against gram-positive and gram-negative bacteria including Pseudomonas aeruginosa, are recommended to use early and sufficiently as empiric first-line therapy for FN. Several beta-lactam antibiotics including imipenem/cilastatin (IPM/CS), meropenem (MEPM), ceftazidime (CAZ) or cefepime (CFPM) have been studied as empirical therapy for FN. However, limited data are available concerning the efficacy of doripenem (DRPM) in FN patients with HEM.Methods: We conducted a randomized, cooperative group, open-label trial comparing DRPM (1.0g every 8 hours) with MEPM (1.0g every 8 hours) as first-line empirical antibacterial treatment for FN patients. 146 hospitalized FN patients with AL during or after chemotherapy were randomized to each drug group (DRPM, 73; MEPM, 73). These study drugs were administered as mono-therapy at least for 5 days without drug toxicity. The efficacy and safety were evaluated.Results: The overall response rate within seven days of DRPM and MEPM were not significantly different (DRPM: 67.3%, MEPM: 52.9%, P = 0.098). Both the resolution of fever by mono-therapy at day 3 to 5 (DRPM: 57.8%, MEPM: 47.4% (p = 0.26)), or survival at day 30 (DRPM: 98.2%, MEPM: 100% (p = 0.312)) was not significantly different in the two groups. Only grade 1-2 adverse events: liver dysfunction, renal dysfunction, diarrhea and rash were observed in some cases, and a little less often in DRPM group (DRPM: 29.8%, MEPM: 40.8% (p = 0.046)). These adverse events were clinically minimal in the two groups, and most of patients could continue the treatment by both study drugs.Conclusions: We could prove the non-inferiority of DRPM in comparison with MEPM for the initial treatment in AL patients with FN. Both drugs were well tolerated as first line therapy for FN.