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JAC Advance Access published online on August 12, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh403
© 2004 by The British Society for Antimicrobial Chemotherapy
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Received April 28, 2004
Revised June 30, 2004
Accepted July 19, 2004

Original article

Continuous and 4 h infusion of amphotericin B: a comparative study involving high-risk haematology patients

A. Y. Peleg 1* M. L. Woods 1

1 Infectious Diseases Unit, Department of Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia

* To whom correspondence should be addressed. E-mail: A.Peleg{at}alfred.org.au; antonpeleg@iprimus.com.au.


  Abstract

Objectives: To assess whether a continuous infusion of amphotericin B (CI-AmB) is less nephrotoxic than a 4 h infusion in haematology patients with fever and neutropenia, including bone-marrow transplant recipients. Efficacy was assessed as a secondary end-point.

Patients and methods: We conducted a retrospective cohort study over a 2 year period. A total of 1073 haematology admissions were reviewed (98.3% complete) and 81 admissions were eligible for study entry; 39 received CI-AmB and 42 a 4 h infusion of AmB.

Results: Renal impairment occurred significantly less frequently with CI-AmB compared with a 4 h infusion of AmB [10% versus 45%, respectively, odds ratio (OR) 0.14; 95% confidence interval (CI) 0.04-0.5, P<0.001]. The difference was maintained among allogeneic transplant recipients (P=0.007) and patients receiving concurrent nephrotoxic drugs (P<0.001). An AmB infusion rate of <0.08 mg/kg/h was associated with a significant reduction in renal impairment (P<0.001). A difference in survival was observed between the continuous and 4 h infusion of AmB (95% versus 79%, respectively, OR 5.1; 95% CI 1.02-25.1, P=0.03).

Conclusions: CI-AmB appears to be significantly less nephrotoxic than 4 h infusion AmB in haematology patients with fever and neutropenia--including high-risk bone-marrow transplant recipients--without increasing mortality. An AmB infusion rate of <0.08 mg/kg/h appears to be a safe threshold, associated with reduced renal impairment.

Keywords: neutropenia; fever of unknown origin; bone-marrow transplantation; nephrotoxicity; antifungal agents.
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