Abstract
Invasive fungal infections have become a major obstacle to the treatment of patients with malignancies. Candida spp. and Aspergillus spp. now rank among the ten most prominent pathogens in these patients. Currently, there are no adequate means of detecting these infections at an early stage, and optimal hygiene and elimination of well-known sources of infection remain the most important preventive measures. Due to the lack of reliable, randomized studies, the role of antifungal drugs in the prevention of invasive fungal infections is difficult to judge. The clinical impact of the older oral antifungal agents is questionable, and compliance with therapeutic regimens of these drugs is often limited. In prospective studies in bone marrow transplant recipients, fluconazole was effective in preventing candidiasis but offered no prophylaxis against infections due to Aspergillus spp. and other molds. Initial trials on the use of sprays and aerosols of amphotericin B and on infusions of low doses of this drug appeared beneficial, but the number of patients included was too small to allow any definite conclusion. Itraconazole offers promise, but it can only be given orally; adequate, reliable absorption is not yet guaranteed. While the lack of data justifies a wait-and-see approach in patients at low or moderate risk of developing a fungal infection, it seems reasonable to administer prophylaxis to high-risk patients, even though there is presently no single agent suitable for all prophylactic purposes.
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References
Saral R:Candida andAspergillus infections in immunocompromised patients. Reviews of Infectious Diseases 1991, 13: 487–492.
Bodey GP, Bueltmann B, Duguid W, Gibbs D, Hanak H, Mall G, Martino P, Meunier F, Milliken S, Naoe S, Okudaira M, Scevola D, van't Wout J: Fungal infections in cancer patients: an international autopsy survey. European Journal of Clinical Microbiology & Infectious Diseases 1992, 11: 99–109.
Martino P, Girmenia C, Venditti M, Girmenia C, Mandelli F:Candida colonization and systemic infection in neutropenic patients. Cancer 1989, 64: 2030–2034.
Verwey PE, Donnelly JP, Kullberg BJ, Meis JFGM, De Pauw BE: Amphotericin B versus amphotericin B plus 4-flucytosine: poor results in the treatment of proven mycoses in neutropenic patients. Infection 1994, 22: 81–85.
Working Party of the British Society for Antimicrobial Chemotherapy: Chemoprophylaxis for candidosis and aspergillosis in neutropenia and transplantation: a review and recommendations. Journal of Antimicrobial Chemotherapy 1993, 32: 5–21.
Palmblad J, Lonnqvist B, Carisson B, Grimfors G, Jarnmark G, Lerner R, Ljungman P, Nystrom-Rosander C, Pertini B, Oberg G: Oral ketoconazole prophylaxis forCandida infections during induction therapy for acute leukemia in adults: more bacteraemias. Journal of Internal Medicine 1992, 231: 363–370.
Goodman JL, Winston DJ, Greenfield RA, Chandrasekar PH, Fox B, Kaizer H, Shadduck RK, Shea T, Stiff P, Friedman DJ, Powderley WG, Silber JL, Horowitz H, Lichtin A, Wolff SN, Nangan KF, Silver SM, Weisdorf D, Ho WG, Gilver 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.
Slavin MA, Osborne B, Adams R, Levenstein MJ, Schoch HG, Feldman AR, Meyers JD, Bowden RA: Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation — a prospective, randomized double blind study. The Journal of Infectious Diseases 1995, 171: 1545–1552.
Alangaden G, Chandrasekar PH, Bailey E, Kaliq Y and the Bone Marrow Transplantation Team: Antifungal prophylaxis with low-dose fluconazole during bone marrow transplantation. Bone Marrow Transplantation 1994, 14: 919–924.
Ninane J, a Multicentre Study Group: A muticentre study of fluconazole versus oral polyenes in the prevention of fungal infection in children with hematological or oncological malignancies. European Journal of Clinical Microbiology & Infectious Diseases 1994, 13: 330–337.
Winston DW, Chandrasekar PH, Lazarus HM, Goodman JL, Silber JL, Horowitz H, Shadduck RK, Rosenfeld CS, Ho WG, 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.
Ellis ME, Clink H, Ernst P, Halim MA, Padmos A, Spence D, Kalin M, Hussain Qadri SM, Burnie J, Greer W: Controlled study of fluconazole in the prevention of fungal infections in neutropenic patients with haematological malignancies and bone marrow transplant recipients. European. Journal of Clinical Microbiology & Infectious Diseases 1994, 13: 3–11.
Philpott-Howard JN, Wade JJ, Mufti GJ, Brammer KW, Ehninger G: Randomized comparison of oral fluconazole versus oral polyenes for the prevention of fungal infection in patients at risk of neutropenia. Journal of Antimicrobial Chemotherapy 1993, 31: 973–984.
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, The GIMIMA 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.
Wingard JR, Merz WG, Rinaldi MG, Johnson TR, Karp JE, Saral R: Increase inCandida krusei infection among patients with bone marrow transplantation and neutropenia treated prophylactically with fluconazole. New England Journal of Medicine 1991, 325: 1274–1277.
Bodey GP, Anaissie EJ, Elting LS, Estey E, Obrien S, Kantarjian H: Antifungal prophylaxis during remission induction therapy for acute leukemia: fluconazole versus intravenous amphotericin B. Cancer 1994, 73: 2099–2106.
Conneally E, Cafferkey MT, Daly PA, Keane CT, McCann SR: Nebulized amphotericin B as prophylaxis against invasive aspergillosis in granulocytopenic patients. Bone Marrow Transplantation 1990, 5: 403–406.
Jeffery GM, Beard MEJ, Ikram RB, Chau J, Allen JR, Heaton DC, Hart DNJ, Schousboe MI: Intranasal amphotericin B reduces the frequency of invasive aspergillosis in neutropenic patients. American Journal of Medicine 1991, 90: 685–692.
Myers SE, Devine SM, Topper RL, Ondrey M, Chandler K, O'Toole K, Williams SF, Larson RA, Geller RB: A pilot study of prophylactic aerosolized amphotericin B in patients at risk for prolonged neutropenia. Leukemia & Lymphoma 1992, 8: 229–233.
Hertenstein B, Kern WV, Schmeiser T, Stefanic M, Bunies D, Wiesneth M, Novotny J, Heimpel H, Arnold R: Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia. Annals of Hematology 1994, 68: 21–26.
Rousey SR, Russler S, Gottlieb M, Ash RC: Low-dose amphotericin B prophylaxis against invasiveAspergillus infections in allogeneic marrow transplantation. American Journal of Medicine 1991, 91: 484–492.
Meunier F: New methods for delivery of antifungal agents. Reviews of infectious Diseases 1989, 11, Supplement 7: 1605–1612.
Perfect J, Klotman ME, Gilbert CC, Crawford DD, Rosner GL, Wright KA, Peters WP: Prophylactic intravenous amphotericin B neutropenic autologous bone marrow transplant recipients. Journal of Infectious Diseases 1992, 165: 891–897.
Riley DK, Pavia AT, Beatty PG, Petersen FB, Spruance JL, Stokes R, Evans TG: The prophylactic use of lowdose amphotericin B in bone marrow transplant patients. American Journal of Medicine 1994, 97: 509–514.
O'Donnell MR, Schmidt GM, Tegtmeier BR, Faucett C, Fahey JL, Ito J, Nademanee A, Niland J, Parker P, Smith EP, Snyder DS, Stein AS, Blume KG, Forman SJ: Prediction of systemic fungal infection in allogeneic marrow reciplents: impact of amphotericin prophylaxis in high-risk patients. Journal of Clinical Oncology 1994, 12: 827–834.
Behre G, Schwartz S, Lenz K, Ludwig W-D, Wandt H, Schilling E, Heinemann V, Link H, Trittin A, Boenisch O, Treder W, Siegert W, Hiddemann W, Beyer J: Aerosol amphotericin B inhalations for the prevention of invasive pulmonary aspergillosis in neutropenic cancer patients. Annals of Hematology 1995, 71: 287–291.
Tollemar J, Ringden O, Andersson S, Sundberg B, Ljungman P, Sparrelid E, Tyden G: Prophylactic use of liposomal amphotericin B (Ambisome) against fungal infections: a randomized trial in bone marrow transplant recipients. Transplantation Proceedings 1993, 25: 1495–1497.
Van't Wout JW, Novakova I, Verhagen CAH, Fibbe WE, De Pauw BE, Van der Meer JWM: The efficacy of itraconazole against systemic fungal infections in neutropenic patients: a randomized comparative study with amphotericin B. British Journal of Infection 1991, 22: 45–52.
Denning DW, Tucker RM, Hanson LH, Stevens DA: Treatment of invasive aspergillosis with itraconazole. American Journal of Medicine 1989, 86: 791–800.
Boogaerts MA, Verhoef GE, Zachee P, Demuynck H, Verbiest L, De Beule K: Antifungal prophylaxis with itraconazole in prolonged neutropenia: correlation with plasma levels. Mycoses 1989, 32, Supplement 1: 103–108.
Thunissen PLM, Sizoo W, Hendriks WDH: Safety and efficacy of itraconazole in prevention of fungal infections in neutropenic patients. Netherlands Journal of Medicine 1991, 39: 84–91.
Prentice AG, Bradford GR: Prophylaxis of fungal infections with itraconazole during remission induction therapy. Mycoses 1989, 32, Supplement 1: 96–102.
Vreugdenhil G, Van Dijke BJ, Donnelly JP, Novakova IRO, Raemaekers JMM, Hoogkamp-Korstanje MAA, De Pauw BE: Efficacy of itraconazole in the prevention of fungal infections among neutropenic patients with hematological malignancies and intensive chemotherapy. A double blind, placebo controlled study. Leukemia & Lymphoma 1993, 11: 353–358.
Boogaerts MA, Verhoef GE, Zachee P: Prophylaxis with itraconazole in prolonged neutropenia: correlation with plasma levels. Mycoses 1989, 32, Supplement 1: 103–108.
Prentice AG, Warnock DW, Johnson SA, Phillips MJ, Oliver DA: Multiple dose pharmacokinetics of an oral solution of itraconazole in autologous bone marrow transplant recipients. Journal of Antimicrobial Chemotherapy 1994, 34: 247–252.
Schaffner A, Böhler A: Amphotericin B refractory aspergillosis after itraconazole: Evidence for significant antagonism. Mycoses 1993, 36: 421–424.
EORTC International Antimicrobia Therapy Cooperative Group: Empiric antifungal therapy in febrile neutropenic patients. American Journal of Medicine 1989, 86: 668–672.
Sanford GR, Merz WG, Wingard JR, Sarache P, Saral R: The value of surveillance cultures as predictors of systemic fungal infections. Journal of Infectious Diseases 1980, 142: 503–509.
Guiot HFL, Fibbe WE, Van't Wout JW: Risk factors for fungal infection in patients with malignant hematological disorders: implications for empirical therapy and prophylaxis. Clinical Infectious Diseases 1994, 18: 525–532.
Morrison VA, Haake RJ, Weisdorf DJ: Non-candidal fungal infections after bone marrow transplantation: risk factors and outcome. American Journal of Medicine 1994, 96: 497–503.
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 1984, 72: 101–107.
Karp JE, Burch PA, Merz WG: An approach to intensive antileukemic therapy in patients with previous invasive aspergillosis. American Journal of Medicine 1988, 85: 203–206.
Cowie F, Meller ST, Cushing P, Pinkerton R: Chemoprophylaxis for pulmonary aspergillosis during intensive chemotherapy. Archives of Disease in Childhood 1994, 70: 136–138.
Denning DW, Lee JY, Hostetler JS, Papppas P, Kaufmann CA, Dewsnup DH, Galgiani JN, Graybill JR, Sugar AM, Catanzaro A, Gallis H, Perfect JR, Dockery B, Dismukes WE, Stevens DA: NIAID mycosis study group multicenter trial of oral itraconazole therapy for invasive aspergillosis. American Journal of Medicine 1994, 97: 135–144.
Martino R, Nomdedéu J, Altés A, Sureda A, Brunet S, Martinez C, Domingo-Albós A: Successful bone marrow transplantation in patients with previous invasive fungal infections: report of four cases. Bone Marrow Transplantation 1994, 13: 265–269.
Nosari A, Cantoni S, Muti G, Cairoli R, Cipriani D, De Cataldo F: Itraconazole in leukemic patients with invasive aspergillosis (IA): impact on intensive chemotherapy completion. European Journal of Haematology 1994, 53: 183–185.
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De Pauw, B.E. Practical modalities for prevention of fungal infections in cancer patients. Eur. J. Clin. Microbiol. Infect. Dis. 16, 32–41 (1997). https://doi.org/10.1007/BF01575119
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DOI: https://doi.org/10.1007/BF01575119