PIPERACILLIN TAZOBACTAM PLUS AMIKACIN VER SUS CEFTAZIDIME PLUS AMIKACIN IN NEUTROPENIC PATIENTS WITH FEVER AN OPEN MULTICENTRIC TRIAL

Objectives: To evaluate the toxicity and effectiveness of piperacillin + tazobactam and amikacin compared with a reference treatment with ce ftazidime and amikacin given as first line therapy in neutropenic pati ents with fever. Methods: A multicentric randomized trial was conducte d in 222 adults who had fever (38 degrees C for > 3 h) during a period of aplasia (white cell count < 0.5.10(9)/I for 22.9 +/- 10.4 days) in duced by chemotherapy for acute leukaemia (68.1%) or by bone marrow au tograft for lymphoma, myeloma or solid tumour (30.3%). 109 patients we re assigned to the piperacillin (12 g/d)/tazobactam (1.5 g/d) + amikac in group and 113 to the ceftazidime (3 gld) + amikacin group. Evaluati on criteria were the frequency of apyrexia after a 72-hour antibiotic regimen and major infectious events defined as death due to infection and severe infections causing a delay in the chemotherapy protocol. Re sults: Data obtained in 188 patients who fulfilled all the protocol cr iteria were evaluated. The episode of fever was controlled better with the piperacillin / tazobactam + amikacin combination (apyrexia achiev ed in 60.6% of the patients vs 44.7% in the ceftazidime + amikacin gro up, p = 0.028) and there were fewer superinfections (23% vs 41% respec tively, p < 0.008). Tolerance was similar in the two groups. In vitro, 56% of the strains resistant to piperacillin and isolated prior to tr eatment were sensitive to the piperacillin / tazobactam combination. A mong the strains isolated (41 Gram-, 61 Gram+), 72% were sensitive to ceftazidime and 84% were sensitive to the piperacillin/tazobactam comb ination. There were 16 deaths due to infection (8.5%) with no differen ce according to antibiotic regimen. There was no difference in toxicit y. Conclusion: Tolerance was similar in the two groups. A combined reg imen of piperacillin/tazobactam can be proposed as first line treatmen t for neutropenic patients with fever.