Current Infectious Disease Reports

, Volume 8, Issue 1, pp 7–13 | Cite as

Empiric antifungal therapy in neutropenic cancer patients


Hematopoietic stem cell transplant recipients and those patients with acute leukemia are at greatest risk for invasive fungal infections particularly due to Candida and Aspergillus species during periods of profound neutropenia. Empiric antifungal therapy in persistently febrile neutropenic patients has been adopted as a standard of care. Antifungal therapeutic options include: amphotericin B, lipid formulations of amphotericin B, fluconazole, itraconazole, voriconazole, and caspofungin. Amphotericin B preparations offer a beneficial effect for survival, defervescence, and a decrease in breakthrough fungal infections. Lipid formulations of amphotericin B may provide beneficial effects over amphotericin B with regard to survival, treatment of baseline fungal infection, breakthrough fungal infection, and fewer discontinuations due to lack of efficacy. Amphotericin B compounds produce a trend for better outcomes in defervescence, treatment of baseline fungal infections, prevention of breakthrough infections, and avoidance of discontinuation compared with the azoles. Caspofungin is also effective. The optimal empiric antifungal agent and the precise time of initiation remain to be determined.


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References and Recommended Reading

  1. 1.
    Sobel JD: Practice guidelines for the treatment of fungal infections. For the Mycoses Study Group. Infectious Diseases Society of America. Clin Infect Dis 2000, 30:652.PubMedCrossRefGoogle Scholar
  2. 2.
    McNeil MM, Nash SL, Hajjeh RA, et al.: Trends in mortality due to invasive mycotic diseases in the United States, 1980–1997. Clin Infect Dis 2001, 33:641–647.PubMedCrossRefGoogle Scholar
  3. 3.
    Wisplinghoff H, Bischoff T, Tallent SM, et al.: Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis 2004, 39:309–317.PubMedCrossRefGoogle Scholar
  4. 4.
    Edmond MB, Wallace SE, McClish DK, et al.: Nosocomial bloodstream infections in United States hospitals: a three-year analysis. Clin Infect Dis 1999, 29:239–244.PubMedGoogle Scholar
  5. 5.
    Rotstein C, Cimino M, Winkley K, et al.: Nosocomial infection rates at an oncology center. Infect Control Hosp Epidemiol 1988, 9:13–19.CrossRefPubMedGoogle Scholar
  6. 6.
    Engelhart D, Glasmacher A, Exner M, Kramer MH: Surveillance for nosocomial infections and fever of unknown origin among adult hematology-oncology patients. Infect Control Hosp Epidemiol 2002, 23:244–248.PubMedCrossRefGoogle Scholar
  7. 7.
    Wingard JR, Leather HL: Empiric antifungal therapy for the neutropenic patient. Oncology 2001, 15:351–369.PubMedGoogle Scholar
  8. 8.
    De La Rosa GR, Champlin RE, Kontoiannis DP: Risk factors for the development of invasive fungal infections in allogeneic blood and marrow transplant recipients. Transpl Infect Dis 2002, 4:3–9.CrossRefGoogle Scholar
  9. 9.
    Wakayam M, Shibuay K, Ando T, et al.: Deep-seated mycosis as a complication in bone marrow transplantation patients. Mycoses 2002, 45:146–151.CrossRefGoogle Scholar
  10. 10.
    Bow E: Invasive fungal infections in patients receiving intensive cytotoxic therapy for cancer. Br J Haematol 1998, 101 (Suppl 1):1–4.PubMedGoogle Scholar
  11. 11.
    Montesinos J, Sola C, Maroto P, et al.: Fungal infections in patients with solid tumors treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Eur J Clin Microbiol Infect Dis 2001, 20:569–572.PubMedCrossRefGoogle Scholar
  12. 12.
    Bow EJ, Laverdiere M, Lussier N, et al.: Antifungal prophylaxis for severely neutropenic chemotherapy recipients: a meta-analysis of randomized-controlled clinical trials. Cancer 2002, 94:3230–3246.PubMedCrossRefGoogle Scholar
  13. 13.
    Rotstein C, Bow EJ, Laverdiere M, et al.: Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian Fluconazole Prophylaxis Study Group. Clin Infect Dis 1999, 28:331–340.PubMedGoogle Scholar
  14. 14.
    Baddley JW: Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis 2001, 32:1319–1324.PubMedCrossRefGoogle Scholar
  15. 15.
    Viscoli C: Candidemia in cancer patients: a perspective, multi-center surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis 1999, 28:1071–1079.PubMedGoogle Scholar
  16. 16.
    Groll AH, Walsh TJ: Uncommon opportunistic fungi: new nosocomial threats. Clin Microbiol Infect 2001, 7(Suppl 2):8–24.PubMedCrossRefGoogle Scholar
  17. 17.
    Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR 2000, 49(RR10):1–128.Google Scholar
  18. 18.
    Hughes WT, Armstrong D, Bodey GP, et al.: 2002 Guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin Infect Dis 2002, 34:730–751. These guidelines are for the use of antimicrobial agents in febrile neutropenic patients with cancer.PubMedCrossRefGoogle Scholar
  19. 19.
    Karp JE, Burch PA, Merz WG: An approach to intensive antileukemia therapy in patients with previous invasive aspergillosis. Am J Med 1988, 85:203–206.PubMedCrossRefGoogle Scholar
  20. 20.
    Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG: Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 1982, 72:101–111.PubMedCrossRefGoogle Scholar
  21. 21.
    EORTC International Antimicrobial Therapy Cooperative Group: Empiric antifungal therapy in febrile granocytopenic patients. Am J Med 1989, 86:668–672.CrossRefGoogle Scholar
  22. 22.
    Heussel CP, Kauczor HU, Heussel GE, et al.: Pneumonia in febrile neutropenic patients and in bone marrow and blood stem-cell transplant recipients: use of high-resolution computed tomography. J Clin Oncol 1999, 17:796.PubMedGoogle Scholar
  23. 23.
    Maertens J, VanEldere J, Verhaegen J, et al.: Use of circulating galactomannan screening for early diagnosis of invasive aspergillosis in allogeneic stem cell transplant recipients. J Infect Dis 2002, 186:1297–1306.PubMedCrossRefGoogle Scholar
  24. 24.
    Klont RR, Mennink-Kersten MA, Verweij PE: Utility of aspergillus antigen detection in specimens other than serum specimens. Clin Infect Dis 2004, 15:1467–1474.CrossRefGoogle Scholar
  25. 25.
    Bennett JE, Powers J, Walsh TJ, et al.: Forum report: issues in clinical trials of empirical antifungal therapy in treating febrile neutropenic patients. Clin Infect Dis 2003, 36(Suppl 3):S117-S122. This article discusses the deficiencies of clinical trials of empiric antifungal therapy.PubMedCrossRefGoogle Scholar
  26. 26.
    Lazarus HM, Lowder JN, Anderson JM, Herzig RH: A prospective randomized trial of central venous catheter removal versus intravenous amphotericin B in febrile neutropenic patients. J Parenter Enteral Nutr 1984, 8:501–505.CrossRefGoogle Scholar
  27. 27.
    Caillot D, Reny G, Solary E, et al.: A controlled trial of the tolerance of amphotericin B infused in dextrose in intralipid in patients with hematological malignancies. J Antimicrob Chemother 1994, 33:603–613.PubMedCrossRefGoogle Scholar
  28. 28.
    White MH, Bowden RA, Sandler ES, et al.: Randomized, double blind clinical trial of amphotericin colloidal dispersion vs amphotericin B in the empirical treatment of fever and neutropenia. Clin Infect Dis 1998, 27:296–302.PubMedGoogle Scholar
  29. 29.
    Prentice HG, Hann IM, Herbrecht R, et al.: A randomized comparison of liposomal vs conventional amphotericin B for the treatment of pyrexia of unknown origin in neutropenic patients. Br J Haemtol 1997, 98:711–718.CrossRefGoogle Scholar
  30. 30.
    Walsh TJ, Finberg RW, Arndt C, et al.: Liposomal amphotericin B for empirical therapy in patients with persistent fever and neutropenia. N Engl J Med 1999, 340:764–771.PubMedCrossRefGoogle Scholar
  31. 31.
    Powles R, Kulkarni S, Treleaven J, et al.: Phase III, randomized trial of nyotran liposomal nystatin or amphotericin B for the empiric antifungal therapy in febrile neutropenic patients [poster]. Presented at the American Society of Hematology, 41st Annual Meeting. New Orleans, LA; December 3–7, 1999:Poster 709.Google Scholar
  32. 32.
    Viscoli C, Castagnola E, Van Lint MT, et al.: Fluconazole vs amphotericin B as empirical antifungal therapy of unexplained fever in granocytopenic cancer patients: a pragmatic, multicentred, prospective in randomized clinical trial. Eur J Cancer 1996, 32A:814–820.PubMedCrossRefGoogle Scholar
  33. 33.
    Winston DJ, Hathorn JW, Schuster MG, et al.: A multicentre, randomized trial of fluconazole vs amphotericin B for empiric antifungal therapy of febrile neutropenic patients with cancer. Am J Med 2000, 108:282–289.PubMedCrossRefGoogle Scholar
  34. 34.
    Boogaerts M, Winston DJ, Bow EJ, et al.: Intravenous and oral itraconazole vs intravenous amphotericin B deoxycholate as empirical antifungal therapy for persistent fever in neutropenic patients with cancer who are receiving broad-spectrum antibacterial therapy. Ann Intern Med 2001, 135:412–422.PubMedGoogle Scholar
  35. 35.
    Walsh TJ, Pappas P, Winston DJ, et al.: Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med 2002, 346:225–234.PubMedCrossRefGoogle Scholar
  36. 36.
    Walsh TJ, Teppler H, Donowitz GR, et al.: Caspofungin vs liposomal amphotericin B for empirical antifungal therapy in patients with persistent fever and neutropenia. N Engl J Med 2004, 351:1391–1402.PubMedCrossRefGoogle Scholar
  37. 37.
    Goldstone AH, O’Driscoll A: Early AmBisome in febrile neutropenia in patients with hematological disorders. Bone Marrow Transplant 1994, 14(Suppl 5):S15–17.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2006

Authors and Affiliations

  1. 1.Henderson SiteHamilton Health SciencesHamiltonCanada

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