Correspondence

Echinocandins for Candidemia

N Engl J Med 2006; 355:2791-2792December 28, 2006

Article

To the Editor:

Bennett (Sept 14 issue)1 did not mention voriconazole as an option for the treatment of candidemia in adults without neutropenia. However, in December 2005, on the basis of a randomized, open-label, comparative, multicenter study involving 422 patients worldwide,2 the Food and Drug Administration approved the use of voriconazole for treating this infection. In this study, voriconazole was shown to be as effective as a regimen of amphotericin B followed by fluconazole. Treatment with voriconazole was better tolerated, and resulted in negative blood cultures as quickly as did treatment with amphotericin B and fluconazole.

Voriconazole has potent activity against pathogenic yeasts, including isolates with reduced susceptibility to fluconazole.3 In addition, it has excellent oral bioavailability. Thus, voriconazole should not be dismissed as an option for the treatment of candidemia. However, in the light of data showing clinically significant cross-resistance between older azole drugs and voriconazole,4 caution is advised when one is considering voriconazole therapy for candidemia in patients previously treated with fluconazole. A randomized trial comparing the efficacy of voriconazole with that of echinocandins for the treatment of candidemia is warranted.

Carolina Garcia-Vidal, M.D.
Jordi Carratalà, M.D.
Hospital Universitari de Bellvitge, 08907 Barcelona, Spain

Dr. Carratalà reports receiving lecture fees from Pfizer.

4 References

1. 1

   Bennett JE. Echinocandins for candidemia in adults without neutropenia. N Engl J Med 2006;355:1154-1159
   Full Text | Web of Science | Medline

2. 2

   Kullberg BJ, Sobel JD, Ruhnke M, et al. Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet 2005;366:1435-1442
   CrossRef | Web of Science | Medline

3. 3

   Ostrosky-Zeichner L, Rex JH, Pappas PG, et al. Antifungal susceptibility survey of 2000 bloodstream Candida isolates in the United States. Antimicrob Agents Chemother 2003;47:3149-3154
   CrossRef | Web of Science | Medline

4. 4

   Panackal AA, Gribskov JL, Staab JF, et al. Clinical significance of azole antifungal drug cross-resistance in Candida glabrata. J Clin Microbiol 2006;44:1740-1743
   CrossRef | Web of Science | Medline

Author/Editor Response

The recently published Swiss guidelines concur with the view of Garcia-Vidal and Carratalà that voriconazole should be considered as one of the second-line agents for treatment of candidemia in nonneutropenic patients with no prior exposure to an azole.1 However, I see no clear indication for selecting voriconazole over fluconazole for such patients. Candida species with reduced susceptibility to fluconazole have proportionally reduced susceptibility to voriconazole. The major indication for the use of voriconazole is its clinical efficacy against invasive mold infections.2 For candidemia, fluconazole is the preferred azole because of its superior safety profile, fewer known drug interactions, and lower cost, and because of the absence of restrictions on intravenous administration in patients with a creatinine clearance below 50 ml per minute.3

John E. Bennett, M.D.
National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892

3 References

1. 1

   Fluckiger U, Marchetti O, Bille J, et al. Treatment options of invasive fungal infections in adults. Swiss Med Wkly 2006;136:447-463
   Web of Science | Medline

2. 2

   Herbrecht R, Denning DW, Patterson TF, et al. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 2002;347:408-415
   Full Text | Web of Science | Medline

3. 3

   Kofla G, Ruhnke M. Voriconazole: review of a broad spectrum triazole antifungal agent. Expert Opin Pharmacother 2005;6:1215-1229
   CrossRef | Web of Science | Medline