[Piperacilline/tazobactam combination+amikacin versus ceftazidime+amikacin in patients with neutropenia and fever. An open multicenter study. Groupe d'étude des Aplasies Fébriles].

Abstract

OBJECTIVES:

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.

CONCLUSION:

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.

• Authors: J P Marie, A Vekhoff, P Cony-Makhoul, D Fière, H Guy, R Herbrecht, N Milpied, J L Pico, I Plantier
• Journal: Presse medicale (Paris, France : 1983) (Presse Med) Vol. 24 Issue 8 Pg. 397-401 (Feb 25 1995) ISSN: 0755-4982 [Print] France
• Vernacular Title: Association pipéracilline/tazobactam+amikacine versus ceftazidime+amikacine chez les patients neutropéniques et fébriles. Etude multicentrique ouverte. Groupe d'étude des Aplasies Fébriles (GAF).
• PMID: 7899419 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• beta-Lactamase Inhibitors
• Amikacin
• Penicillanic Acid
• Ceftazidime
• Tazobactam
• Piperacillin

Topics

• Adult
• Aged
• Amikacin (adverse effects, therapeutic use)
• Ceftazidime (adverse effects, therapeutic use)
• Drug Therapy, Combination (adverse effects, therapeutic use)
• Fever (complications, drug therapy, microbiology)
• Humans
• Middle Aged
• Neutropenia (complications, drug therapy, microbiology)
• Penicillanic Acid (adverse effects, analogs & derivatives, therapeutic use)
• Piperacillin (adverse effects, therapeutic use)
• Tazobactam
• beta-Lactamase Inhibitors