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 (PT) in a large randomized trial. Two hundred-eight febrile neutropenic episodes (FNE) (> or = 38.5 degrees C and ANC < or = 0.5 giga/l) were treated by randomization, as first line therapy, using either CPO 2 g x 2/day (105 cases) or PT 4 g x 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 microbiologically 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 PT 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 PT 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 PT (p = 0.27) and 53% versus 40% respectively in the 151 cases with neutropenia > or = 10 days (p = 0.17). The occurrence of side effects was similar in both arms. In our hands, the efficacy of CPO and PT was comparable for treating FNE.

Historical Cohort Study of the Efficacy and Safety of Piperacillin/Tazobactam Versus Fourth-Generation Cephalosporins for Empirical Treatment of Febrile Neutropenia in Patients with Hematological Malignancies

“…In the present study, the overall efficacy rate was 57.0% in the 4th Cephs group and 59.2% in the P/T group. Similar to our findings, the efficacy rates of 4th Cephs ± aminoglycoside and PIPC/TAZ ± aminoglycoside in cases of FN reported from previous controlled studies varied at 21-62% and 27%-61%, respectively [12][13][14][15]. This variability in the efficacy rates noted in these studies is likely related to differences in the definition of efficacy, which was variously set as 2-or 3-day defervescence, microbiological eradication, test of cure, and so on.…”

“…The third limitation of this study is that the antimicrobials were given to the patients at 9:00, 15:00, and 21:00 hours, taking into account the patients' sleeping times and the nursing shifts. As reported elsewhere, intravenous antimicrobial infusion should desirably be given at 8-hour intervals according to the antimicrobial pharmacokinetics/pharmacodynamics [12][13][14][15].…”

Cefpirome. Literature review

“…3 rd -4 th -generation cephalosporins featuring anti-pseudomonas aeruginosa activity (ceftazidime or cefepime), carbapenems or "protected" anti-pseudomonas aeruginosa penicillins (ticarcillin/clavulanate or piperacillin/tazobactam) are the 1 st line drugs for FN. Supplementation of the aforementioned drugs with aminoglycosides does not improve treatment results [16,17]. F. Bauduer et al [17] assessed results of a randomized multicenter study, where cefpirome (4 g/day) or piperacillin/tazobactam (12 g/day) were used as the 1 st line drugs for chemotherapy-induced FN in patients with oncohematological diseases.…”

“…Supplementation of the aforementioned drugs with aminoglycosides does not improve treatment results [16,17]. F. Bauduer et al [17] assessed results of a randomized multicenter study, where cefpirome (4 g/day) or piperacillin/tazobactam (12 g/day) were used as the 1 st line drugs for chemotherapy-induced FN in patients with oncohematological diseases. 208 FN episodes were analyzed: 10 cases out of them concerned allotransplantation of stem cells, 38 -autologous transplantation thereof.…”

Determination of Nontoxic Concentrations of Piperacillin/Tazobactam for Intravitreal Application

“…Although piperacillin/tazobactam is currently used with high success against most serious infections [ [14][15][16][17][18][30][31][32][33], there are no clinical trials using piperacillin/tazobactam in the treatment of endophthalmitis. In addition, intravitreal safe dose of piperacillin/tazobactam combination has not been studied yet.…”