Drew J. Winston, MD; Winston G. Ho, MD; David A. Bruckner, ScD; Richard E. Champlin, MD
▪ Objective: To compare the efficacy, toxicity, and cost-effectiveness of double beta-lactam therapy with monotherapy.
▪ Design: A randomized, controlled trial.
▪ Patients: Febrile, granulocytopenic patients (429).
▪ Interventions: Patients were randomly assigned to receive iv cefoperazone (3 g every 12 hours) plus piperacillin (75 mg/kg body weight every 6 hours), ceftazidime (2 g every 8 hours) plus piperacillin (75 mg/kg every 6 hours), or imipenem alone (1.0 g or 0.5 g every 6 hours). Patients also received prophylactic vitamin K.
▪ Measurements: Clinical improvement, eradication of the infecting organism, and toxicity in 403 evaluable patients with one or more infections.
▪ Main Results: Cefoperazone and ceftazidime, when given in combination with piperacillin, were equally effective (response rates of 75% (104 of 138 patients) and 74% (101 of 137 patients), respectively). Monotherapy with imipenem had a response rate of 82% (111 of 136 patients) and was as effective as double beta-lactam therapy. Overall antibiotic-related toxicity was minimal, although seizures were associated with high doses of imipenem. Seizures occurred in 3 of 29 patients (10.3%) who were receiving 4 g/d of imipenem, in 3 of 136 patients (2.2%) who were receiving cefoperazone plus piperacillin, in 0 of the 132 patients who were receiving ceftazidime plus piperacillin, and in 1 of 106 patients (0.9%) who were receiving 2 g/d of imipenem (P < 0.005). The 2-g daily dose of imipenem was as effective as the 4-g daily dose. Diarrhea was more frequent in patients receiving cefoperazone, whereas nausea occurred more often with imipenem. No antibiotic-related hemorrhage or nephrotoxicity was observed. Superinfections caused by betalactam-resistant, gram-negative bacilli were uncommon but occurred more frequently with double beta-lactam therapy than with imipenem monotherapy (11 of 268 patients compared with 1 of 135 patients; P = 0.06). Xanthomonas maltophilia superinfections occurred only in patients receiving imipenem (3 of 135 patients compared with 0 of 268 patients; P = 0.03). Imipenem monotherapy was the least expensive therapy.
▪ Conclusions: Cefoperazone and ceftazidime were equally effective when used in combination antibiotic therapy with piperacillin. Twice-daily cefoperazone is less expensive than ceftazidime given three times daily. Monotherapy with imipenem, at a daily dose of 2 g, is as efficacious as double beta-lactam therapy and costs less than combination therapy.
Winston DJ, Ho WG, Bruckner DA, et al. Beta-Lactam Antibiotic Therapy in Febrile Granulocytopenic Patients: A Randomized Trial Comparing Cefoperazone plus Piperacillin, Ceftazidime plus Piperacillin, and Imipenem Alone. Ann Intern Med. 1991;115:849–859. doi: 10.7326/0003-4819-115-11-849
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Published: Ann Intern Med. 1991;115(11):849-859.
Diarrhea, Emergency Medicine, Gastroenterology/Hepatology, Hematology/Oncology, Infectious Disease.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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