[Piperacilline/tazobactam combination+amikacin versus ceftazidime+amikacin in patients with neutropenia and fever. An open multicenter study. Groupe d'étude des Aplasies Fébriles].
OBJECTIVE
To evaluate the toxicity and effectiveness of piperacillin+tazobactam and amikacin compared with a reference treatment with ceftazidime and amikacin given as first line therapy in neutropenic patients with fever.


METHODS
A multicentric randomized trial was conducted in 222 adults who had fever (38 degrees C for > 3 h) during a period of aplasia (white cell count < 0.5.10(9)/l for 22.9 +/- 10.4 days) induced by chemotherapy for acute leukaemia (68.1%) or by bone marrow autograft for lymphoma, myeloma or solid tumour (30.3%). 109 patients were assigned to the piperacillin (12 g/d)/tazobactam (1.5 g/d)+amikacin group and 113 to the ceftazidime (3 g/d)+amikacin group. Evaluation 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.


RESULTS
Data obtained in 188 patients who fulfilled all the protocol criteria were evaluated. The episode of fever was controlled better with the piperacillin/tazobactam+amikacin combination (apyrexia achieved in 60.6% of the patients vs 44.7% in the ceftazidime+amikacin group, p = 0.028) and there were fewer superinfections (23% vs 41% respectively, p < 0.008). Tolerance was similar in the two groups. In vitro, 56% of the strains resistant to piperacillin and isolated prior to treatment were sensitive to the piperacillin/tazobactam combination. Among the strains isolated (41 Gram-, 61 Gram+), 72% were sensitive to ceftazidime and 84% were sensitive to the piperacillin/tazobactam combination. There were 16 deaths due to infection (8.5%) with no difference according to antibiotic regimen. There was no difference in toxicity.


CONCLUSIONS
Tolerance was similar in the two groups. A combined regimen of piperacillin/tazobactam can be proposed as first line treatment for neutropenic patients with fever.
Marie
J P
JP
Services d'Hématologie: Hôtel-Dieu, Paris.
Vekhoff
A
A
Cony-Makhoul
P
P
Fière
D
D
Guy
H
H
Herbrecht
R
R
Milpied
N
N
Pico
J L
JL
Plantier
I
I
D000328:Adult; D000368:Aged; D000583:Amikacin / Q000009:adverse effects / Q000627:therapeutic use; D002442:Ceftazidime / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000627:therapeutic use*; D005334:Fever / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D010397:Penicillanic Acid / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D010878:Piperacillin / Q000009:adverse effects / Q000627:therapeutic use; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors
D065093:beta-Lactamase Inhibitors; D000583:Amikacin; D010397:Penicillanic Acid; D002442:Ceftazidime; D000078142:Tazobactam; D010878:Piperacillin
Association pipéracilline/tazobactam+amikacine versus ceftazidime+amikacine chez les patients neutropéniques et fébriles. Etude multicentrique ouverte. Groupe d'étude des Aplasies Fébriles (GAF).