title: Ceftazidime compared with piperacillin and tobramycin for the empiric treatment of fever in neutropenic patients with cancer. A multicenter randomized trial. The Intercontinental Antimicrobial Study Group.
abstract: OBJECTIVE
  To compare piperacillin and tobramycin with ceftazidime alone for the empiric treatment of fever in the neutropenic patient without evidence of skin infections or anaerobic infections.
  
  
  METHODS
  A multicenter, randomized, controlled trial.
  
  
  METHODS
  876 febrile, neutropenic episodes in 696 patients (83% acute leukemia or bone marrow transplantation); 92 episodes were excluded from analysis because of protocol violation.
  
  
  METHODS
  Patients received either intravenous ceftazidime (2 g every 8 h) or piperacillin (12 to 18 g/d in 4 to 6 divided doses plus tobramycin (1.7 to 2.0 mg/kg body weight every 8 h). Treatment could be modified at any time at the discretion of the investigator.
  
  
  METHODS
  Percentage of satisfactory response, eradication of the infecting organism, development of superinfections, and occurrence of adverse events.
  
  
  RESULTS
  As a single agent, ceftazidime was as effective as the combination of piperacillin and tobramycin (62.7% satisfactory responses compared with 61.1%; odds ratio, 1.07%; 95% Cl, 0.79 to 1.44; P > 0.2). Equivalent responses were also obtained in episodes of profound neutropenia (odds ratio, 0.76; Cl, 0.43 to 1.33; P > 0.2). Infectious mortality was 6% for ceftazidime and 8% for the combination therapy. Eradication of the infecting organisms was achieved in 79% of bacteremic episodes treated with ceftazidime compared with 68% of the episodes treated with the combination therapy (odds ratio, 1.76; Cl, 0.92 to 3.38; P = 0.08), and rates for gram-negative rod bacteremia were also similar (95% compared with 77%; odds ratio, 5.25; Cl, 1.0 to 27.5; P = 0.03). Superinfections developed in 38 episodes in each group. An adverse event occurred in 8% of episodes treated with ceftazidime compared with 20% of episodes treated with combination therapy (P < 0.001).
  
  
  CONCLUSIONS
  Ceftazidime alone was as effective but safer than the combination of piperacillin and tobramycin for the empiric treatment of febrile, neutropenic patients, even those with profound and prolonged granulocytopenia.
authors.affiliation: Division of Hematology, University Hospital St. Radboud, Nijmegen, The Netherlands.
authors.forename: B E
authors.initials: BE
authors.lastname: De Pauw
authors.forename: S C
authors.initials: SC
authors.lastname: Deresinski
authors.forename: R
authors.initials: R
authors.lastname: Feld
authors.forename: E F
authors.initials: EF
authors.lastname: Lane-Allman
authors.forename: J P
authors.initials: JP
authors.lastname: Donnelly
mesh_terms: D000328:Adult; D016470:Bacteremia / Q000188:drug therapy; D002442:Ceftazidime / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005334:Fever / Q000382:microbiology*; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D009503:Neutropenia / Q000150:complications* / Q000209:etiology; D016017:Odds Ratio; D010878:Piperacillin / Q000009:adverse effects / Q000627:therapeutic use; D015163:Superinfection / Q000209:etiology; D014031:Tobramycin / Q000009:adverse effects / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D002442:Ceftazidime; D014031:Tobramycin; D010878:Piperacillin