Beta-Lactam Antibiotic Therapy in Febrile Granulocytopenic Patients

作者：Drew J. Winston, Winston G. Ho, David A. Bruckner, Richard E. Champlin · 发表于：Annals of Internal Medicine · 年份：1991 · DOI：10.7326/0003-4819-115-11-849 · 被引用次数：162 · 研究领域：Antibiotics Pharmacokinetics and Efficacy、Antibiotic Use and Resistance、Antibiotic Resistance in Bacteria

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 less than 0.005). The 2-g daily dose of imipenem was as effective as the...