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Ceftazidime Compared with Piperacillin and Tobramycin for the Empiric Treatment of Fever in Neutropenic Patients with Cancer: A Multicenter Randomized Trial

Ben E. De Pauw, MD, PhD; Stanley C. Deresinski, MD; Ronald Feld, MD; Elizabeth F. Lane-Allman, CBiol; and J. Peter Donnelly, MBiol, PhD
[+] Article, Author, and Disclosure Information

For participating investigators and institutions, committee members, and current author addresses, see Appendix 1, Appendix 2, and end of text. For The Intercontinental Antimicrobial Study Group. Requests for Reprints: Ben E. De Pauw, MD, PhD, Division of Hematology, University Hospital St. Radboud, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands. Grant Support: Glaxo Group Research, Ltd., Greenford, Middlesex, United Kingdom, and its local subsidiaries financed the collection of data or supplied the study drugs free of charge.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1994;120(10):834-844. doi:10.7326/0003-4819-120-10-199405150-00004
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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.

Design: A multicenter, randomized, controlled trial.

Patients: 876 febrile, neutropenic episodes in 696 patients (83% acute leukemia or bone marrow transplantation); 92 episodes were excluded from analysis because of protocol violation.

Interventions: 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.

Measurements: 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% CI, 0.79 to 1.44; P > 0.2). Equivalent responses were also obtained in episodes of profound neutropenia (odds ratio, 0.76; CI, 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; CI, 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; CI, 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).

Conclusion: 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.


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Figure 2.
Kaplan-Meier plot of the time to first modification.P

The plots are effectively superimposed ( > 0.2).

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Figure 3.
Cumulative rate of defervescence.P

Only around one third of patients had become afebrile by day 3 of treatment, whereas rates of defervescence were virtually identical ( > 0.2).

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Figure 4.
Comparison of satisfactory responses among the different regions.

Odds ratios are shown together with their 95% CIs, indicating that neither regimen was favored.

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