An open study on the safety and efficacy of fluconazole in the treatment of disseminated Candida infections in patients treated for hematological malignancy

Annals of Hematology - Tập 70 - Trang 83-87 - 1995
B. E. de Pauw1, J. M. M. Raemaekers1, J. P. Donnelly1, B. -J. Kullberg1, J. F. G. M. Meis1
1Departments of Hematology, Medical Microbiology, Internal Medicine, University Hospital St. Radboud, HB Nijmegen, The Netherlands

Tóm tắt

Disseminated candidiasis is a serious infectious complication with a mortality as high as 50%. Standard therapy consists of parenteral amphotericin B which is associated with major side effects and prolonged hospitalization. The aim of the study was to assess the efficacy and safety of fluconazole in an open, noncomparative study. Fluconazole, as a single agent, was given intravenously for the first 3 days at a dose of 200 mg twice daily, followed by 200 mg twice daily orally until resolution of signs and symptoms or evident treatment failure. The study group comprised 24 consecutive patients of whom nine had acute and 15 chronic disseminated candidiasis. A clinical response was achieved in 67% of cases of acute disseminated candidiasis and in 86% of cases of chronic disseminated candidiasis. The median duration of therapy was 15 days and 6 months, respectively. Superinfections withAspergillus fumigatus developed in five patients who were persistently neutropenic. No drug-related toxicity was registered.

Tài liệu tham khảo

Anaissie EJ, Bodey GP, Kantarjian H (1991) Fluconazole therapy for chronic disseminated candidiasis in patients with leukemia and prior amphotericin B therapy. Am J Med 91:142–150 Anaissie EJ, Darwiche R, Mera J, Gentry L, Abi-Said D, Bodey GP (1993) A prospective randomized multicenter study comparing fluconazole to amphotericin B for nosocomial candidiasis. Abstract book XVIII Intersc Conf Antimicrob Agents Chemother, New Orleans abstr. 808 Bodey GP, Bueltman B, Duguid W, et al (1992) Fungal infections in cancer patients; an international autopsy survey. Eur J Clin Microbiol Infect Dis 11:99–109 Bone RC, Fisher CJ, Clemmer TP, et al (1989) Sepsis syndrome: a valid clinical entity. Crit Care Med 17:389–393 Callen PW, Filly RA, Marcus FS (1980) Ultrasonography and computed tomography in the evaluation of hepatic microabscesses in the immunocompromised patient. Radiology 136:433–434 Espinall-Ingroff A, Kish CW, Kerkering TM, et al (1992) Collaborative comparison of broth macrodilution and microdilution antifungal susceptibility tests. J Clin Microbiol 30:3138–3145 Evans TG, Mayer J, Cohen S, et al (1991) Fluconazole failure in the treatment of systemic mycoses. J Infect Dis 164:1232–1235 Goodman JL, Winston DJ, Greenfield RA, et al (1992) A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med 326:845–851 Grant SM, Clissold SP (1990) Fluconazole. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses. Drugs 39:877–916 Haron E, Feld R, Tuffnell P, Patterson B, Hasselback R, Matlow A (1987) Hepatic candidiasis: an increasing problem in immunocompromised patients. Am J Med 83:17–26 Kaufman CA, Bradley SF, Ross SC, Weber DR (1991) Hepatosplenic candidiasis: successful treatment with fluconazole. Am J Med 91:137–141 Kappe R, Osterziel KJ, Rüchel R, Siehl S (1993) Fluconazole in patients at risk from invasive aspergillosis. J Med Vet Mycol 31:259–261 Linker CA, DeGregoria MW, Ries CA (1984) Computerized tomography in the diagnosis of systemic candidiasis in patients with acute leukemia. Med Pediatr Oncol 12:380–385 Meunier F., Aoun M, Bitar N (1992) Candidemia in immunocompromised patients. Clin Infect Dis 14 [Suppl 1]:S120-S125 Milatovic D, Voss A (1992) Efficacy of fluconazole in the treatment of systemic fungal infections. Eur J Clin Microbiol Infect Dis 11:395–402 Saral R (1991)Candida andAspergillus infections in immunocompromised patients: an overview. Rev Infect Dis 13:487–492 Sickles EA, Greene WH, Wiernik PH (1975) Clinical presentation of infection in granulocytopenic patients. Arch Intern Med 135:715–719 Thaler M, Pastakia B, Shawker TH, O'Leary T, Pizzo PA (1988) Hepatic candidiasis in cancer patients: the evolving picture of the syndrome. Ann Intern Med 108:88–100 Van 't Wout JW, Mattie H, Van Furth R (1988) A prospective study of the efficacy of fluconazole (UK-49,858) against deepseated fungal infections. J Antimicrob Chemother 21:665–672 Van 't Wout JW, Novakova I, Verhagen CAH, Fibbe WE, De Pauw BE, Van der Meer JWM (1991) The efficacy of itraconazole against systemic fungal infections in neutropenic patients: a randomised comparative study with amphotericin B. J Infect 22:45–52 Viscoli C, Castagnola E, Fioredda F, Ciravegna B, Barigione G, Terragna A (1991) Fluconazole in the treatment of candidiasis in immunocompromised children. Antimicrob Agents Chemother 35:365–367 Vreugdenhil G, Van Dijke BJ, Donnelly P, et al (1993) Efficacy of itraconazole in the prevention of fungal infections among neutropenic patients with hematological malignancies and intensive chemotherapy. A double-blind, placebo-controlled study. Leuk Lymphoma 11:353–358 Wingard JR, Merz WG, Rinaldi MG, Miller CB, Karp JE, Saral R (1993) Association ofTorulopsis glabrata infections with fluconazole prophylaxis in neutropenic bone marrow transplant patients. Antimicrob Agents Chemother 37:1847–1849 Winston DJ, Chandrasekar PH, Lazarus HM, et al (1993) Fluconazole prophylaxis of fungal infections in patients with acute leukemia. Ann Intern Med 118:495–503