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Previous Volume 346:225-234 January 24, 2002 Number 4 Next

	Full Text PDF PDA Full Text Perspective by Corey, L. Editorial by Marr, K. A. Letters Letters Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited Related Article

ABSTRACT

Background Patients with neutropenia and persistent fever are often treated empirically with amphotericin B or liposomal amphotericin B to prevent invasive fungal infections. Antifungal triazoles offer a potentially safer and effective alternative.

Methods In a randomized, international, multicenter trial, we compared voriconazole, a new second-generation triazole, with liposomal amphotericin B for empirical antifungal therapy.

Results A total of 837 patients (415 assigned to voriconazole and 422 to liposomal amphotericin B) were evaluated for success of treatment. The overall success rates were 26.0 percent with voriconazole and 30.6 percent with liposomal amphotericin B (95 percent confidence interval for the difference, –10.6 to 1.6 percentage points); these rates were independent of the administration of antifungal prophylaxis or the use of colony-stimulating factors. There were fewer documented breakthrough fungal infections in patients treated with voriconazole than in those treated with liposomal amphotericin B (8 [1.9 percent] vs. 21 [5.0 percent], P=0.02). The voriconazole group had fewer cases of severe infusion-related reactions (P<0.01) and of nephrotoxicity (P<0.001). The incidence of hepatotoxicity was similar in the two groups. Patients receiving voriconazole had more episodes of transient visual changes than those receiving liposomal amphotericin B (22 percent vs. 1 percent, P<0.001) and more hallucinations (4.3 percent vs. 0.5 percent, P<0.001). Parenteral voriconazole was changed to the oral formulation in 22 percent of the voriconazole group, with a reduction in the mean duration of hospitalization by one day in all patients (P=0.17) but by two days in patients at high risk (P=0.03).

Conclusions Voriconazole is a suitable alternative to amphotericin B preparations for empirical antifungal therapy in patients with neutropenia and persistent fever.

Source Information

From the National Cancer Institute, Bethesda, Md. (T.J.W.); the University of Alabama, Birmingham (P.P.); the University of California, Los Angeles (D.J.W.); the University Hospitals of Cleveland, Cleveland (H.M.L.); the University of Utah, Salt Lake City (F.P.); New York Medical College, New York (J.R.); the Medical College of Virginia, Richmond (S.Y.); Loyola University Medical Center, Chicago (P.S.); the University of Kentucky, Lexington (R.G.); the University of Virginia, Charlottesville (G.D.); and the National Institute of Allergy and Infectious Diseases Mycoses Study Group, Birmingham, Ala. (J.L.).

Other authors were Mindy Schuster, M.D. (University of Pennsylvania, Philadelphia); Annette Reboli, M.D. (Cooper Hospital, Camden, N.J.); John Wingard, M.D. (University of Florida, Gainesville); Carola Arndt, M.D. (Mayo Clinic, Rochester, Minn.); John Reinhardt, M.D. (Medical Center of Delaware, Newark); Susan Hadley, M.D. (Beth Israel Deaconess Medical Center, Boston); Robert Finberg, M.D. (Dana–Farber Cancer Institute, Boston); Michél Laverdière, M.D. (Maisonneuve–Rosemont Hospital, Montreal); John Perfect, M.D. (Duke University, Durham, N.C.); Gary Garber, M.D. (University of Ottawa, Ottawa, Ont., Canada); Giuseppe Fioritoni, M.D. (Ospedaliero della ASL di Pescara, Pescara, Italy); and Eli Anaissie, M.D. (University of Arkansas, Little Rock).

Address reprint requests to Dr. Walsh at the Immunocompromised Host Section, National Cancer Institute, Bldg. 10, Rm. 13N240, Bethesda, MD 20892.

Full Text of this Article

Related Letters:

Voriconazole versus Liposomal Amphotericin B for Empirical Antifungal Therapy
Johnson J. R., Ullmann A. J., Heussel C. P., Cornely O. A., Apisarnthanarak A., Little J. R., Tebas P., Walsh T. J., Pappas P. G., Winston D. J.
Extract | Full Text | PDF  
N Engl J Med 2002; 346:1745-1747, May 30, 2002. Correspondence

Voriconazole versus Liposomal Amphotericin B in Patients with Neutropenia and Persistent Fever
Powers J. H., Dixon C. A., Goldberger M. J.
Extract | Full Text | PDF  
N Engl J Med 2002; 346:289-290, Jan 24, 2002. Correspondence

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