Prospective study ofCandida colonization, use of empiric amphotericin B and development of invasive mycosis in neutropenic patients

  • P. Martino
  • C. Girmenia
  • A. Micozzi
  • F. De Bernardis
  • M. Boccanera
  • A. Cassone


The association between colonization withCandida spp., subsequent occurrence of invasive candidiasis and empiric use of amphotericin B was investigated prospectively in 139 neutropenic patients with hematologic malignancies. Treatment with amphotericin B was required in 67 % of patients colonized in multiple non-contiguous body sites (multicolonized) versus 31 % of patients colonized in single or contiguous sites (monocolonized) and in 21 % of non-colonized patients (p=0.0037 and p=0.00026, respectively). Invasive candidiasis was documented in 22.2 % of multicolonized versus 4.8 % of monocolonized patients and in none of the non-colonized patients (p=0.035 and p=0.0036, respectively). Analysis of the spectrum of colonizingCandida spp. showed that multicolonized subjects were colonized with increased frequency byCandida albicans compared to monocolonized subjects, and that the association between multicolonization, invasive candidiasis and amphotericin B usage was statistically significant in patients colonized byCandida albicans but not in patients colonized by otherCandida species. The association betweenCandida multicolonization and the occurrence ofCandida infection seems to be confirmed by a double-blind placebo-controlled study performed in a small subgroup of the multicolonized patients treated with fluconazole.


  1. 1.
    Stein RS, Kayser J, Flexner JM: Clinical value of empirical amphotericin B in patients with acute myelogenous leukemia. Cancer 1982, 50: 2247–2251.PubMedGoogle Scholar
  2. 2.
    Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG: Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. American Journal of Medicine 1982, 72: 101–111.CrossRefPubMedGoogle Scholar
  3. 3.
    EORTC International Antimicrobial Therapy Cooperative Group: Empiric antifungal therapy in febrile granulocytopenic patients. American Journal of Medicine 1989, 86: 668–672.Google Scholar
  4. 4.
    Walsh TJ, Lee J, Lecciones J, Rubin M, Butler K, Francis P, Weinberger M, Roilides E, Marshall D, Gress J, Pizzo PA: Empiric therapy with amphotericin B in febrile granulocytopenic patients. Reviews of Infectious Diseases 1991, 13: 496–503.PubMedGoogle Scholar
  5. 5.
    Perfect JR, Pickard WW, Hunt DL, Palmer B, Schell WA: The use of amphotericin B in nosocomial fungal infections. Reviews of Infectious Diseases 1991, 13: 474–479.PubMedGoogle Scholar
  6. 6.
    Sandford GR, Merz WG, Wingard JR, Charache P, Saral R: The value of fungal surveillance cultures as predictors of systemic fungal infections. Journal of Infectious Diseases 1980, 142: 503–509.PubMedGoogle Scholar
  7. 7.
    Bodey GP: Fungal infections complicating acute leukemia. Journal of Chronic Diseases 1966, 19: 667–687.CrossRefPubMedGoogle Scholar
  8. 8.
    Meunier-Carpentier F, Kiehn TE, Armstrong D: Fungemia in the immunocompromised host. Changing patterns, antigenemia, high mortality. American Journal of Medicine 1981, 71: 363–370.CrossRefPubMedGoogle Scholar
  9. 9.
    De Gregorio MW, Lee WMF, Linker CA, Ries CA: Candida infections in patients with acute leukemia: ineffectiveness of nystatin prophylaxis and relationship between oropharyngeal and systemic candidiasis. Cancer 1982, 50: 2780–2784.PubMedGoogle Scholar
  10. 10.
    Martino P, Girmenia C, Venditti M, Micozzi A, Santilli S, Burgio VL, Mandelli F: Candida colonization and systemic infections in neutropenic patients. Cancer 1989, 64: 2030–2034.PubMedGoogle Scholar
  11. 11.
    Wingard JR, Merz WG, Saral R:Candida tropicalis: a major pathogen in immunocompromised patients. Annals of Internal Medicine 1979, 91: 539–543.PubMedGoogle Scholar
  12. 12.
    Meunier F: Prevention of mycoses in immunocompromised patients. Reviews of Infectious Diseases 1987, 9: 408–416.PubMedGoogle Scholar
  13. 13.
    Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, Shadduck RK, Shea TC, Stiff P, Friedman DJ, Powderly WG, Silber JL, Horowitz H, Lichtin A, Wolff SN, Mangan KF, Silver SM, Weinsdorf D, Winston G, Gilbert G, Buell D: A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. New England Journal of Medicine 1992, 326: 845–851.Google Scholar
  14. 14.
    Winston DJ, Chandrasekar PH, Lazarus HM, Goodman JL, Silber JL, Horowitz H, Shadduck RK, Rosenfeld CS, Winston GH, Islam MZ, Buell DN: Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Results of a randomized placebo-controlled, double-blind, multicenter trial. Annals of Internal Medicine 1993, 118: 495–503.PubMedGoogle Scholar
  15. 15.
    Menichetti F, Del Favero A, Martino P, Bucaneve G, Micozzi A, D'Antonio D, Ricci P, Carotenuto M, Liso V, Nosari AM, Barbui T, Fasola G, Mandelli F, andthe GIMEMA Infection Program: Preventing fungal infection in neutropenic patients with acute leukemia: fluconazole compared with oral amphotericin B. Annals of Internal Medicine 1994, 120: 913–918.PubMedGoogle Scholar
  16. 16.
    Venditti M, De Bernardis F, Micozzi A, Pontieri E, Chirletti P, Cassone A, Martino P: Fluconazole treatment of catheter-related right-sided endocarditis caused byCandida albicans and associated with endophthalmitis and folliculitis. Clinical Infectious Diseases 1992, 14: 422–426.PubMedGoogle Scholar
  17. 17.
    Aisner J, Murillo J, Schimpff SC, Steere AC: Invasive aspergillosis in acute leukemia: correlation with nose cultures and antibiotic use. Annals of Internal Medicine 1979, 90: 4–9.PubMedGoogle Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlagsgesellschaft mbH 1994

Authors and Affiliations

  • P. Martino
    • 1
  • C. Girmenia
    • 1
  • A. Micozzi
    • 1
  • F. De Bernardis
    • 2
  • M. Boccanera
    • 2
  • A. Cassone
    • 2
  1. 1.Section of Hematology, Department of Human BiopathologyUniversity “La Sapienza”RomeItaly
  2. 2.Department of Bacteriology and Medical MycologyIstituto Superiore di Sanita’RomeItaly

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