Systemic Azole Antifungal Drugs — Into the 1990s

  • John R. Graybill
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 96)


Amphotericin B marked the beginning of the real antifungal era. Beginning with the 1960s, there was a broad spectrum antifungal drug that could be administered parenterally and could arrest the course of devastating systemic fungal infections. Amphotericin B revolutionized the treatment of the major endemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis) and also provided the first effective therapy for cryptococcal meningitis. Were efficacy the only relevant question today, it would still be difficult to find treatment significantly superior to amphotericin B. However, the toxicity of amphotericin B and the need for intravenous administration have made prolonged therapeutic regimens difficult to administer. In addition, the relative rarity of systemic fungal infections was an insufficient stimulus for pharmaceutical companies to undertake the increasingly costly investment required to identify and develop new classes of drugs for systemic mycoses.


Antimicrob Agent Neutropenic Patient Cryptococcal Meningitis Systemic Mycosis Antifungal Azole 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Arndt CAS, Walsh TJ, McCully CL, Balis FM, Pizzo PA, Poplack DG (1988) Fluconazole penetration into cerebrospinal fluid: implications for treating fungal infections of the central nervous system. J Inf Dis 157:178–180Google Scholar
  2. Bennett JE, Remington JS (1981) Miconazole in cryptococcosis and systemic candidiasis: a word of caution. Ann Int Med 94:708–709Google Scholar
  3. Bodey GP (1984) Candidiasis in cancer patients. Am J Med 77 ()Suppl 4 D:13–19Google Scholar
  4. Boogaerts MA, Van De Pitte K, Verhoef G, Zachee P, De Beule K (1988) Itraconazole (ITRA) prophylaxis of invasive fungal infection in prolonged neutropenia. Abstract 576. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los Angeles (Abstr 576)Google Scholar
  5. Borelli D (1987) A clinical trial of itraconazole in the treatment of deep mycoses and leishmaniasis. Rev Inf Dis 9: S57–S63Google Scholar
  6. Bradsher RW, Rice DC, Abernathy RS (1985) Ketoconazole therapy for endemic blastomycosis. Ann Int Med 103: 872–879PubMedGoogle Scholar
  7. Brass C, Galgiani JN, Blaschke TF, DeFelice R, O’Reilly RA, Stevens DA (1982) Disposition of ketoconazole, an oral antifungal, in humans. Antimicrob Agents Chemother 27:151–158Google Scholar
  8. Britton H, Shebab Z, Lightner E, New M, Chow D (1988) Adrenal response in children receiving high doses of ketoconazole for systemic coccidioidomycosis. J Pediatrics 112:488–492Google Scholar
  9. Bronnimann DA, Adam RD, Gagliani JN, Habib MP, Peterson EA, Porter B, Bloom JW (1987) Coccidioidomycosis in the acquired immunodeficiency syndrome. Ann Int Med 106:372–379PubMedGoogle Scholar
  10. Brown MW, Maldonado AL, Meredith CG, Speeg KV (1985) Effect of ketoconazole on hepatic oxidative drug metabolism. Clin Pharmacol Ther 37:290–297PubMedGoogle Scholar
  11. Bru JP, Lebeau B, Stahl JP, Micoud M (1988) Oral fluconazole treatment of urinary mycoses. Revista Ibérica de Micológia 5 (Supplement 1): 34 (abstract 0–94)Google Scholar
  12. Buchsbaum HW, Fahs JJ, Friedman BA (1985) Coccidioidal meningitis treated with high-dose ketoconazole. In: Einstein HE, Catazano A (eds) Coccidioidomycosis. Proceedings of the 4th International Conference. National Foundation for Infectious Diseases, Washington DC, p 438Google Scholar
  13. Calhoun DL, Galgiani JN, Stevens DA, Waskin H, Bonner JR, White MP, Mulholland JH, Rumans LW (1986) Ketoconazole treatment of Sporothrix schenckii arthritis and other infections. Abstract 780. Twenty-sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, New OrleansGoogle Scholar
  14. Catanzaro A, Einstein H, Levine B, Ross JB, Schillaci R, Fierer J, Friedman PJ (1982) Ketoconazole for treatment of disseminated coccidioidomycosis. Ann Int Med 96:436–440PubMedGoogle Scholar
  15. Cauwenbergh G, De Doncker P, Stoops K, De Dier AM, Goyvaerts H, Schuermans V (1987) Itraconazole in the treatment of human mycoses: review of three years of clinical experience. Rev Inf Dis 9: S146–S152Google Scholar
  16. Craven PC, Graybill JR, Jorgensen JH, Dismukes WE, Levine BE (1983) High-dose ketoconazole for treatment of fungal infections of the central nervous system. Ann Int Med 98:160–167PubMedGoogle Scholar
  17. Daneshmend TK, Warnock DW (1988) Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinetics 14:13–34Google Scholar
  18. DeFelice R, Galgiani JN, Campbell SC, Palpant SD, Friedman BA, Dodge RA, Weinberg MG, Lincoln LJ, Tennican PO, Barbee RA (1982) Ketoconazole treatment of nonprimary coccidioidomycosis. Am J Med 72: 681–687Google Scholar
  19. De Gans J, Eeftinck Schattenkert JKM, Van Ketel RJ (1988) Itraconazole as maintenance treatment for cryptococcal meningitis in the acquired immunodeficiency syndrome. Br Med J 296:339Google Scholar
  20. Deresinski SC, Stevens DA (1979) Bone and joint coccidioidomycosis treated with miconazole. Am Rev Resp Dis 120: 1101–1107PubMedGoogle Scholar
  21. Deresinski SC, Lilly RB, Levine HB, Galgiani JN, Stevens DA (1977) Treatment of fungal meningitis with miconazole. Arch Int Med 137: 1180–1185Google Scholar
  22. Deschamps MM, Pape JW, Verdier RI, De Hovits J, Thomas F, Johnson W, (1988) Treatment of Candida esophagitis in AIDS patients. Am J Gastroenterol 83: 20–21PubMedGoogle Scholar
  23. De Wit S, Weeris D, Hermans P, De Cock F, Clumeck N (1988) Double-blind randomized study of oral fluconazole (F) versus ketoconazole (K) in 40 episodes of oropharyngeal candidiasis (OC) in ARC/AIDS patients. Abstract 572. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherpay, Los AngelesGoogle Scholar
  24. Dieperink H, M0ller J (1982) Ketoconazole and cyclosporin. Lancet ii:1217Google Scholar
  25. Dismukes WE (1988) Cryptococcal meningitis in patients with AIDS. J Inf Dis 157:624–628Google Scholar
  26. Dismukes WE, Stamm AM, Graybill JR, Craven PC, Stevens DA, Stiller RL, Sarosi GA, Medoff G, Gregg CR, Gallis HA, Fields BT, Maner RL, Kerkering TA, Kaplowitz LG, Cloud G, Bowles C, Shadomy S (1983) Treatment of systemic mycoses with ketoconazole: emphasis on toxicity and clinical response in 52 patients. Ann Int Med 98: 13–20PubMedGoogle Scholar
  27. Duarte PA, Chow CC, Simmons F, Ruskin J (1984) Fatal hepatitis associated with ketoconazole therapy. Arch Int Med 144:1069–1070Google Scholar
  28. Dupont B, Drouhet E (1985) Cutaneous, ocular, and osteroarticular candidiasis in heroin addicts: new clinical and therapeutic aspects in 38 patients. J Inf Dis 152:577–591Google Scholar
  29. Dupont B, Drouhet E (1988) The treatment of aspergillosis with azole derivatives. In: Vanden Bossche H, Mackenzie DWR, Cauwenbergh G (eds) Aspergillus and aspergillosis. Plenum, New York, pp 243–251Google Scholar
  30. Eng RHK, Bishburg E, Smith SM, Kapila R (1986) Cryptococcal infections in patients with acquired immune deficiency syndrome. Am J Med 81:19–23PubMedGoogle Scholar
  31. Engelhard D, Stutman HR, Marks MI (1984) Interactions of ketoconazole with rifampin and isoniazid. N Engl J Med 311:1681–1683PubMedGoogle Scholar
  32. Fainstein V, Bodey GP (1980) Cardiorespiratory toxicity due to miconazole. Ann Int Med 93:432–433PubMedGoogle Scholar
  33. Fainstein V, Bodey GP, Elting L, Maksymiuk A, Keating M, McCredie KB (1987) Amphotericin B or ketoconazole therapy of fungal infections in neutropenic cancer patients. Antimicrob Agents Chemother 31:11–15PubMedGoogle Scholar
  34. Farrow PR, Brammer KW, Feczko JM (1987) Fluconazole: a new treatment for oropharyngeal candidiasis in AIDS and malignancy. Abstract 949. Twenty- seventh Interscience Conference on Antimicrobial Agents and Chemotherapy, New YorkGoogle Scholar
  35. Farwell AP, Devlin JT, Stewart JA (1988) Total suppression of Cortisol excretion by ketoconazole in the therapy of the ectopic adrenocorticotropic hormone syndrome. Am J Med 84:1063–1066PubMedGoogle Scholar
  36. Fazio RA, Wickremeshinghe PC, Arsura EL (1983) Ketoconazole treatment of Candida esophagitis: a prospective study of 12 cases. Am J Gastroenterol 78:261–264PubMedGoogle Scholar
  37. Ferguson RM, Sutherland DER, Simmons RL, Najarian JS (1982) Ketoconazole, cyclosporin metabolism, and renal transplantation. Lancet ii: 882–883Google Scholar
  38. Galgiani JN (1987) Antifungal susceptibility tests. Antimicrob Agents Chemother 31: 1867–1870PubMedGoogle Scholar
  39. Galgiani JN, Stevens DA, Graybill JR, Stevens DL, Tillinghast AJ, Levine HB (1984) Pseudallescheria boydii infections treated with ketoconazole. Clinical evaluations of seven patients and in vitro susceptibility results. Chest 86:219–224PubMedGoogle Scholar
  40. Galgiani JN, Stevens DA, Graybill JR, Dismukes WE, Cloud GA (1988) Ketoconazole therapy of progressive coccidioidomycosis. Comparison of 400- and 800-mg doses and observations at higher doses. Am J Med 84:603–610PubMedGoogle Scholar
  41. Ganer A, Arathoon E, Stevens DA (1987) Initial experience in therapy for progressive mycoses with itraconazole, the first clinically studied triazole. Rev Inf Dis 9:S77–S86Google Scholar
  42. Graybill JR (1988) Histoplasmosis and AIDS. J Inf Dis 158:623–626Google Scholar
  43. Graybill JR, Levine HB (1978) Successful treatment of cryptococcal meningitis with intraventricular miconazole. Arch Intern Med 138:814–816PubMedGoogle Scholar
  44. Graybill JR, Lundberg D, Donovan W, Levine HB, Rodriguez MD, Drutz DJ (1980) Treatment of coccidioidomycosis with ketoconazole: clinical and laboratory studies of 18 patients. Rev Inf Dis 2:661–673Google Scholar
  45. Graybill JR, Galgiani JN, Jorgensen JH, Strandberg DA (1983a) Ketoconazole therapy for fungal urinary tract infections. J Urol 129:68–70PubMedGoogle Scholar
  46. Graybill JR, Kaster SR, Drutz DJ (1983b) Comparative activities of BAY n7133, ICI 153,066, and ketoconazole in murine cryptococcosis. Antimicrob Agents Chemother 24:829–834PubMedGoogle Scholar
  47. Graybill JR, Stevens DA, Galgiani JN, Dismukes WE, Cloud G, Ganer A, Arathoon E, Fetchick R, Diaz M (1986) Itraconazole treatment of coccidioidomycosis. Abstract 788. Twenty-sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, New OrleansGoogle Scholar
  48. Graybill JR, Sharkey PK, Watson C (1988) Fluconazole treatment of funguria. Revista Ibérica de Micológia 5 (Supplement l):p 34 (abstract 0–93)Google Scholar
  49. Hann IM, Corringham R, Keaney M, Noone P, Fox J, Szawatkowski M, Prentice HG, Blacklock HA, Shannon M, Gascoigne E, Boesen E, Hoffbrand AV (1982) Ketoconazole versus nystatin plus amphotericin B for fungal prophylaxis in severely immunocompromised patients. Lancet i: 826–829Google Scholar
  50. Hardin TC, Graybill JR, Fetchick R, Woestenborghs R, Rinaldi MG, Kuhn JG (1988) Pharmacokinetics of itraconazole following oral administration to normal volunteers. Antimicrob Agents Chemother 32:1310–1313PubMedGoogle Scholar
  51. Harrison HR, Galgiani JN, Reynolds AF, Sprenger LW, Friedman AD (1983) Amphotericin B and imidazole therapy of coccidioidal meningitis in children. Pediatr Infect Dis 2:216–221PubMedGoogle Scholar
  52. Hector RF (1988) Evaluation of the azole BAY R 3783 in rodent models of candidiasis and cryptococcosis. Revista Ibérica de Micológia 5 (Suppl 1): 11 (abstract 0–4)Google Scholar
  53. Heel RC (1982) Coccidioidomycosis. In: Le vine HB (ed) Ketoconazole in the management of fungal disease. ADIS Press, New York, pp 132–135Google Scholar
  54. Hobbs MM, Wright KA, Perfect JR, Tso CY, Durack DT (1988) Efficacy of SCH39304 and fluconazole in the treatment of experimental fungal infections. Abstract 166. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  55. Horn R, Wong B, Kiehn TE, Armstrong D (1985) Fungemia in a cancer hospital: changing frequency, earlier onset, and results of therapy. Rev Inf Dis 7: 646–655Google Scholar
  56. Horsburgh CR, Cannady PB, Kirkpatrick CH (1983) Treatment of fungal infections in the bones and joints with ketoconazole. J Inf Dis 147: 1064–1069Google Scholar
  57. Houston JB, Humphrey MJ, Matthew DE, Tarbit MH (1988) Comparison of two azole antifungal drugs, ketoconazole and fluconazole, as modifiers of rat hepatic monooxygenase activity. Biochem Pharmacol 37:401–408PubMedGoogle Scholar
  58. Humphrey MJ, Jevons S, Tarbit MH (1985) Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug in animals and humans. Antimicrob Agents Chemother 28: 648–653PubMedGoogle Scholar
  59. Janssen PAJ, Symoens JE (1983) Hepatic reactions during ketoconazole treatment. Am J Med 74 (Suppl lB): 80–85PubMedGoogle Scholar
  60. Johnson PC, Khardori N, Najjar AF, Butt F, Mansell PWA, Sarosis GA (1988) Progressive disseminated histoplasmosis in patients with acquired immunodeficiency syndrome. Am J Med 85: 152–158PubMedGoogle Scholar
  61. Jordan WM, Bodey GP, Rodriguez V, Ketchel SJ, Henney J (1979) Miconazole therapy for treatment of fungal infections in cancer patients. Antimicrob Agents Chemother 16: 792–797PubMedGoogle Scholar
  62. Kobayashi G, Travis SJ, Medoff G (1988) In vitro evaluation of Sch39304, fluconazole (FLU), and amphotericn B (AmB) against 12 clinical isolates of Histoplasma capsulatum (Hc) and comparison of therapeutic efficacies in treating histoplasmosis in immunocompetent and immunosuppressed mice. Abstract 172. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  63. Kovacs JA, Kovacs AA, Polis M, Wright WC, Gill VJ, Tuazon CU, Gelmann EP, Lane HC, Longfield R, Overturf G, Macher AM, Fauci AS, Parillo JE, Bennett JE, Masur M (1985) Cryptococcosis in the acquired immunodeficiency syndrome. Ann Int Med 103:533–538PubMedGoogle Scholar
  64. Kramer W, Kim H, Symchowicz S, Perentesis G, Affrime M, Lin C (1988) Pharmacokinetics of SCH39304 in man. Abstract 165. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  65. Kwong YL, Yu YL, Chan FL, Lam KSL, Woo E, Huang CY (1987) High dose ketoconazole in the treatment of cerebral aspergilloma. Clin Neurol Neurosurg 89:193–196PubMedGoogle Scholar
  66. Lake-Bakaar G, Tom W, Lake-Bakaar D, Gupta N, Beidas S, Elsakr M, Straus E (1988) Gastropathy and ketoconazole malabsorption in the acquired immunodeficiency syndrome ( AIDS ). Ann Int Med 109:471–473PubMedGoogle Scholar
  67. Lavalle P, Súchil P, De Ovando F, Reynoso S (1987) Itraconazole for deep mycoses: preliminary experience in Mexico. Rev Inf Dis 9: S64–S70Google Scholar
  68. Lelawongs P, Barone JA, Colaizzi JL, Hsuan AM, Mechlinski W, Legendre RL, Guarnieri J (1988) Effect of food and gastric acidity on absorption of orally administered ketoconaole. Clin Pharmacol 7:228–235Google Scholar
  69. Lewis JH, Zimmerman HJ, Benson GD, Ishak KG (1984) Hepatic injury associated with ketoconazole therapy: analysis of 33 cases. Gastroenterology 86:503–513PubMedGoogle Scholar
  70. Loebenberg D, Parmegiani R, Cacciapuoti A, Antonacci C, Norris C, Menzel F, Moss EL, Yarosh-Tomaine T, Lin CC, Hare RS, Miller GH (1988) Sch 39304, a new antifungal agent. I. Oral treatment of systemic infections in mice. Abstract 167. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  71. Maksymiuk AW, Thongprasert S, Hopfer S, Luna M, Fainstein V, Bodey G (1984) Systemic candidiasis in cancer patients. Am J Med 77 (Suppl 4D): 20–27PubMedGoogle Scholar
  72. McKinsey DS, Gupta MR, Riddler SA, Driks MR, Smith DL, Kurtin PJ (1989) Long- term amphotericin B therapy for disseminated histoplasmosis in patients with the acquired immunodeficiency syndrome ( AIDS ): Ann Int Med 111:655–659Google Scholar
  73. Meunier-Carpentier F (1984) Chemoprophylaxis of fungal infections. Am J Med 76: 652–656PubMedGoogle Scholar
  74. Meunier-Carpentier F, Heymans C, Snoeck R, Taterman J (1983) Interaction of rifampin (Rif) with ketoconazole (Ke) and Bay n7133 (Bay) in normal volunteers. Abstract 987. Twenty-third Interscience Conference on Antimicrobial Agents and Chemotherapy, Las VegasGoogle Scholar
  75. Meyer RD, Sattler FR, Linne SR, Ruskin J (1978) Miconazole for treatment of disseminated coccidioidomycosis: unfavorable experience. Chest 73:25–831PubMedGoogle Scholar
  76. Miettinen TA (1988) Cholesterol metabolism during ketoconazole treatment in man. J Lipid Res 29:43–51PubMedGoogle Scholar
  77. Morgans ME, Thomas MEM, Mackenzie DWR (1979) Successful treatment of systemic cryptococcosis with miconazole. Br Med J 2:100–101PubMedGoogle Scholar
  78. Morgenstern GR, Powles R, Robinson B, McElwain TJ (1982) Cyclosporin interaction with ketoconazole and melphalan. Lancet ii:1342Google Scholar
  79. National Institute of Allergy and Infectious Diseases Mycoses Study Group (1985) Treatment of blastomycosis and histoplasmosis with ketoconazole. Ann Int Med 103:861–872Google Scholar
  80. Negroni R, Robles AM, Arechavala A, Tuculet MA, Galimberti R (1980) Ketoconazole in the treatment of paracoccidioidomycosis and histoplasmosis. Rev Inf Dis 2:643–649Google Scholar
  81. Negroni R, Palmieri O, Koren F, Tiraboschi IN, Galimberti R (1987) Oral treatment of paracoccidioidomycosis and histoplasmosis with itraconazole in humans. Rev Inf Dis 9:S47–S50Google Scholar
  82. Phillips P, Fetchick R, Weisman I, Foshee S, Graybill JR (1987) Tolerance to and efficacy of itraconazole in treatment of systemic mycoses: preliminary results. Rev Inf Dis 9:S87–S93Google Scholar
  83. Pillans PI, Cowan P, Whitelaw D (1985) Hyponatremia and confusion in a patient taking ketoconazole. Lancet i:821–822Google Scholar
  84. Pizzo PA, Robichaud KJ, Gill FA, Witebsky FG (1982) Empiric antibiotic and antifungal therapy for cancer patients with prolonged fever and granulocytopenia. Am J Med 72:101–111PubMedGoogle Scholar
  85. Plempel M, Büchel KH (1988) Antimycotic effects of BAY R 3783 in vitro and on dermatophytoses and opportunistic mycoses of the organs in vivo. Abstract 0–7. Revista Ibérica de Micológia 5 (Suppl 1): 11Google Scholar
  86. Pont A, Graybill JR, Craven PC, Galgiani JN, Dismukes WE, Reitz RE, Stevens DA (1984) High-dose ketoconazole therapy and adrenal and testicular function in humans. Arch Intern Med 144:2150–2153PubMedGoogle Scholar
  87. Restrepo A, Gomez I, Canio LE, Arango MD, Gutierrez F, Sanin A, Robledo MA (1983) Treatment of paracoccidioidomycosis with ketaconazole: a three year experience. Am J Med 74 (lB):48–52PubMedGoogle Scholar
  88. Restrepo A, Robledo J, Gomez I, Tabares AM, Gutierrez R (1986) Itraconazole therapy in lymphangitic and cutaneous sporotrichosis. Arch Dermatol 122:413–417PubMedGoogle Scholar
  89. Restrepo A, Gomez I, Robledo J, Patino MM, Cano LE (1987) Itraconazole in the treatment of paracoccidioidomycosis: a preliminary report. Rev Inf Dis 9:S51–S56Google Scholar
  90. Restrepo A, Gonzalez A, Gomez I, Arango M, De Bedout C (1988a) Treatment of chromoblastomycosis with itraconazole. Ann N Y Acad Sci 544:504–516PubMedGoogle Scholar
  91. Restrepo A, Munera MI, Atreaga ID, Gomez I, Tabares AM, Patino MM, Arango M (1988b) Itraconazole in the treatment of pulmonary aspergilloma and chronic pulmonary aspergillosis. In: Vanden Bossche H, Mackenzie DWR, Cauwenbergh G (eds) Aspergillus and aspergillosis. Plenum, New York, pp 253–265Google Scholar
  92. Restrepo BI, Ahrens J, Graybill JR (1988c) Efficacy of SCH393904 (SCH) in murine cryptococcosis. Abstract 170. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  93. Ross JB, Levine B, Catanzaro A, Einstein H, Schillaci R, Friedman PJ (1982) Ketoconazole for treatment of chronic pulmonary coccidioidomycosis. Ann Int Med 96:440–443PubMedGoogle Scholar
  94. Rozenberg-Arska M, Dekker AW, Verhoff J (1988) Efficacy of fluconazole (FL) for prevention of fungal infections (FI) in comparison to amphotericin B (AmB) in granulocytopenic patients (pts). Abstract 577. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  95. Saag MS, Dismukes WE (1988) Treatment of histoplasmosis and blastomycosis. Chest 93: 848–851PubMedGoogle Scholar
  96. Saag M, Bradsher R, Chapman S, Kauffman C, Girard W, Stevens D, Bowles-Patton C, Dismukes WE (1988) Itraconazole (I) therapy (Rx) for blastomycosis (B), histoplasmosis (H), and sporotrichosis (S). Abstract 574. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  97. Schmitt HJ, Barnard EM, Hauser M, Armstrong D (1988) Comparison of antifungal agents in a rat model of pulmonary aspergillosis. Abstract 171. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  98. Schulman J, Peyman G, Fiscella R, Small G, Coast M, Wajszczuk C, Steahly L (1987) Toxicity of intravitreal injection of fluconazole in the rabbit. Can J Ophthalmol 22:304–306PubMedGoogle Scholar
  99. Shale DJ, Faux JA, Lane DJ (1987) Trial of ketoconazole in noninvasive pulmonary aspergillosis. Thorax 42:26–31PubMedGoogle Scholar
  100. Sharkey PK, Rinaldi MG, Lerner C, Fetchick R, Dunn JF, Graybill JR (1988) High dose itraconazole in the treatment of severe mycoses. Abstract 575. Twenty- eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  101. Shehab ZM, Britton H, Dunn JH (1988) Imidazole therapy of coccidioidal meningitis in children. Pediatric Infect Dis J 7:40–44Google Scholar
  102. Shepp DH., Klosterman A, Siegel MS, Meyers JD (1985) Comparative trial of ketoconazole and nystatin for prevention of fungal infection in neutropenic patients treated in a protective environment. J Inf Dis 152:1257–1263Google Scholar
  103. Smith AG (1984) Potentiation of oral anticoagulants by ketoconazole. Br Med J 288: 188–189Google Scholar
  104. Smith JM, Hows JM, Gordon-Smith EC, Baughan A, Goldman JM (1983) Interaction of CyA and ketoconazole. Clin Sci 64:67P–68PGoogle Scholar
  105. Sonino N (1987) The use of ketoconazole as an inhibitor of steroid production. N Engl J Med 317:812–818PubMedGoogle Scholar
  106. Stern JJ, Hartman BJ, Sharkey PK, Rowland V, Squires KE, Murray HW, Graybill JR (1988) Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients. Am J Med 85:477–480PubMedGoogle Scholar
  107. Stevens DA (1977) Miconazole in the treatment of systemic fungal infections. Am Rev Resp Dis 116:801–806PubMedGoogle Scholar
  108. Stevens DA (1983) Miconazole in the treatment of coccidioidomycosis. Drugs 26:347–354PubMedGoogle Scholar
  109. Stevens DA, Stiller RL, Williams PL, Sugar AM (1983) Experience with ketoconazole in three major manifestations of progressive coccidioidomycosis. Am J Med 74 (Suppl lB):58–63PubMedGoogle Scholar
  110. Stockley RJ, Daneshmend TK, Bredow MT, Warnock DW, Richardson MD, Slade RR (1983) Ketoconazole pharmacokinetics during chronic dosing in adults with hematological malignancy. Eur J Clin Microbiol 5:513–517Google Scholar
  111. Sugar AM, Saunders C (1988) Oral fluconazole as suppressive therapy of disseminated cryptoccosis in patients with acquired immunodeficiency syndrome. Am J Med 85:481–489PubMedGoogle Scholar
  112. Sugar AM, Alsip S, Galgiani JN, Graybill JR, Dismukes WE, Cloud GA, Craven PC, Stevens DA (1987) Pharmacology and toxicity of high dose ketoconazole. Antimicrob Agents Chemother 31:1874–1878PubMedGoogle Scholar
  113. Sung JP, Grendahl JG, Fresno MA, Levine HB (1977) Intravenous and intratheal miconazole therapy for systemic mycosis. West J Med 126: 5–13PubMedGoogle Scholar
  114. Sung JP, Campbell GD, Grendahl JG (1978) Miconazole therapy for fungal meningitis. Arch Neurol 35:443–447PubMedGoogle Scholar
  115. Thaler M, Pastakia B, Shawker TH, O’Leary T, Pizzo PA (1988) Hepatic candidiasis in cancer patients: the evolving picture of the syndrome. Ann Int Med 108:88–100PubMedGoogle Scholar
  116. Thomas PA, Rajasekaran J (1988) Treatment of Aspergillus keratitis with imidazoles and related compounds. In: Vanden Bossche H, Mackenzie DWR, Cauwenbergh G (eds) Aspergillus and aspergillosis. Plenum, New York, pp 267–279Google Scholar
  117. Tricot G, Joosten E, Boogaerts MA, Vande Pitte J, Cauwenbergh G (1987) Ketoconazole vs itraconazole for antifungal prophylaxis in patients with severe granulocytopenia: preliminary results of two nonrandomized studies. Rev Inf Dis 9:S94–S99Google Scholar
  118. Tucker RM, Denning DW, Rinaldi MG, Hanson LH, Stevens DA (1988a) Itraconazole (IZ) therapy (Rx) of progressive coccidioidomycosis (C). Abstract 573. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  119. Tucker RM, Williams PL, Arathoon EG, Levine BE, Hartstein AI, Hanson LH, Stevens DA (1988b) Pharmacokinetics of fluconazole in cerebrospinal fluid and serum in human coccidioidal meningitis. Antimicrob Agents Chemother 32:369–373PubMedGoogle Scholar
  120. Tucker RM, Galgiani JN, Graybill JR, Denning DW, Hanson LH, Eckman MR, Salemi C, Stevens DA (1990) Treatment of coccidioidal meningitis with fluconazole. Rev Inf Dis (in press)Google Scholar
  121. Tucker WS, Snell BB, Island DP, Gregg CR (1985) Reversible adrenal insufficiency induced by ketoconazole. JAMA 253:2413–2414PubMedGoogle Scholar
  122. Van Cauteren H, Heykants J, De Coster R, Cauwenbergh G (1987) Itraconazole: pharmacologic studies in animals and humans. Rev Inf Dis 9:S43–S46Google Scholar
  123. Van Cutsem J (1983) The antifungal activity of ketoconazole. Am J Med 74 (Suppl 1B):9–15PubMedGoogle Scholar
  124. Van Cutsem J, Janssen PAJ (1988) Oral and parenteral treatment of invasive aspergillosis in non-predisposed and in immunocompromised guinea pigs with saperconazole (R66905) and parenteral treatment with amphotericin B. Abstract 176. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  125. Van Cutsem J, Van Gerven F, Janssen PAJ (1987) Activity of orally, topically, and parenterally administered itraconazole in the treatment of superficial and deep mycoses: animal models. Rev Inf Dis 9:S15–S32Google Scholar
  126. Vanden Bossche H (1985) Biochemical targets for antifungal azole derivatives: hypothesis on the mode of action. In: McGinnis M (ed) Current topics in medical mycology. Springer-Verlag, Berlin Heidelberg New York, pp 313–351Google Scholar
  127. Viviáni MA, Tortorano AM, Woenstenborghs R, Cauwenbergh G (1987) Experience with itraconazole in deep mycoses in northern Italy. Mykosen 30:233–244PubMedGoogle Scholar
  128. Walsh TJ, Aoki S, Mechinaud F, Foulds G, Rubin M, Pizzo PA (1988a) Treatment of disseminated candidiasis with fluconazole in persistently granulocytopenic rabbits. Abstract P-165. Revista Ibérica de Micológia 5 (Suppl 1): 92Google Scholar
  129. Walsh TJ, Lee JW, Peter J, Schaufele R, Rubin M, Pizzo PA (1988b) SCH-39304 in the treatment of disseminated candidiasis in persistently granulocytopenic and non-granulocytopenic rabbits. Abstract 169. Twenty-eighth Interscience Conference on Antimicrobial Agents and Chemotherapy, Los AngelesGoogle Scholar
  130. Weinstein L, Jacoby I (1980) Successful treatment of cerebral cryptococcoma and meningitis with miconazole. Ann Int Med 93:569–571PubMedGoogle Scholar
  131. White MC, Kendall-Taylor P (1985) Adrenal hypofunction in patients taking ketoconazole. Lancet i: 44–45Google Scholar
  132. Wingard JR, Vaughan WP, Braine HG, Merz WG, Sarai R (1987) Prevention of fungal sepsis in patients with prolonged neutropenia: a randomized, double-blind, placebo-controlled trial of intravenous miconazole. Am J Med 83:1103–1110PubMedGoogle Scholar
  133. Wise GJ, Goldberg PE, Kozinn PJ (1985) Do the imidazoles have a role in the management of genitourinary fungal infections? J Urol 133:61–64PubMedGoogle Scholar
  134. Zuger A, Schuster M, Simberkoff MS, Rahal JJ, Holzman RS (1988) Maintenance amphotericin B for cryptococcal meningitis in the acquired immunodeficiency syndrome ( AIDS ). Ann Int Med 109:592–593PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1990

Authors and Affiliations

  • John R. Graybill

There are no affiliations available

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