A Randomized Prospective Multicentre Trial of Cefpirome Versus Piperacillin-Tazobactam in Febrile Neutropenia

Abstract

Fever is frequently the only clinical sign of infection in patients with chemo-induced neutropenia. In this setting, empirical administration of broad spectrum antibiotics must be rapid. The aim of this work was to compare, for the first time, cefpirome (CPO) and piperacillin-tazobactam (FT) in a large randomized trial. Two hundred-eight febrile neutropenic episodes (FNE) (≥ 38,5°C and ANC < 0.5 giga/1) were treated by randomization, as first line therapy, using either CPO 2 g × 2/day (105 cases) or FT 4 g × 3/day (103 cases), alone (CPO: 15/PT: 15), or plus aminoglycoside (165 cases, CPO: 82/PT: 83) or quinolone (CPO: 2/PT: 2). There were 131 men and 77 women aged between 17 and 83 years (median: 49) who received chemotherapy (n=160) or allogeneic (n=10) or autologous (n=38) stem cell transplantations. Underlying diseases were: acute leukemia (n=131), lymphoma (n=33), myeloma (n=16), solid tumor (n=8), myeloproliferative disorder (n=9), chronic lymphoid leukemia (n=5), aplastic anemia (n=3), myelodysplasia (n=3). Distribution of age, neutropenia duration (median: 17 days), underlying disease, and protocol therapy duration (median: 11 days) was comparable in both arms. A rnicrobiologically documented infection (MDI) was evidenced in 57 cases (27%). Bacteria were isolated from blood cultures in 54 cases (Gram positive: 32 cases). Their in vitro susceptibility rates to CPO and FT were not different. Two days after antibiotics initiation, clinical (fever disappearance) and microbiological (culture negativation) success rates (SR) were 62% for CPO versus 61% for FT and 50% versus 55% respectively in case of MDI (p = 0.89). Two deaths and 77 failures were registered. At the end of protocol, SR (no antibiotic change/absence of superinfection) was 59% with CPO versus 50% with FT (p = 0.27) and 53% versus 40% respectively in the 151 cases with neutropenia ≥ 10 days (p = 0.17). The occurrence of side effects was similar in both arms. In our hands, the efficacy of CPO and FT was comparable for treating FNE.