title: Beta-lactam antibiotic therapy in febrile granulocytopenic patients. A randomized trial comparing cefoperazone plus piperacillin, ceftazidime plus piperacillin, and imipenem alone.
abstract: OBJECTIVE
  To compare the efficacy, toxicity, and cost-effectiveness of double beta-lactam therapy with monotherapy.
  
  
  METHODS
  A randomized, controlled trial.
  
  
  METHODS
  Febrile, granulocytopenic patients (429).
  
  
  METHODS
  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.
  
  
  METHODS
  Clinical improvement, eradication of the infecting organism, and toxicity in 403 evaluable patients with one or more infections.
  
  
  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 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 beta-lactam-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.
authors.affiliation: UCLA Center for Health Sciences.
authors.forename: D J
authors.initials: DJ
authors.lastname: Winston
authors.forename: W G
authors.initials: WG
authors.lastname: Ho
authors.forename: D A
authors.initials: DA
authors.lastname: Bruckner
authors.forename: R E
authors.initials: RE
authors.lastname: Champlin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000380:Agranulocytosis / Q000150:complications*; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000209:etiology; D002438:Cefoperazone / Q000627:therapeutic use; D002442:Ceftazidime / Q000627:therapeutic use; D003365:Costs and Cost Analysis; D004359:Drug Therapy, Combination / Q000627:therapeutic use; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D010878:Piperacillin / Q000627:therapeutic use; D015163:Superinfection / Q000209:etiology
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem; D002438:Cefoperazone; D002442:Ceftazidime; D010878:Piperacillin