Oral fluconazole therapy for patients with acquired immunodeficiency syndrome and cryptococcosis: experience with 22 patients

• Published in: The American journal of medicine Vol. 85; no. 4; pp. 477 - 480
• Main Authors: Stern, John J., Hartman, Barry J., Sharkey, Patricia, Rowland, Veronica, Squires, Kathleen E., Murray, Henry W., Graybill, J. Richard
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.1988
• Subjects: Acquired Immunodeficiency Syndrome - complications; Administration, Oral; Adolescent; Adult; Antifungal Agents - administration & dosage; Antifungal Agents - adverse effects; Antifungal Agents - therapeutic use; Antigens, Fungal - analysis; Cryptococcosis - complications; Cryptococcosis - drug therapy; Cryptococcosis - microbiology; Cryptococcus neoformans; Cryptococcus neoformans - immunology; Cryptococcus neoformans - isolation & purification; Fluconazole; Humans; Male; Meningitis - complications; Meningitis - drug therapy; Meningitis - microbiology; Middle Aged; Pneumonia - complications; Pneumonia - drug therapy; Pneumonia - microbiology; Triazoles - administration & dosage; Triazoles - adverse effects; Triazoles - therapeutic use
• ISSN: 0002-9343; 1555-7162
• DOI: 10.1016/S0002-9343(88)80081-0

Cryptococcus neoformans causes infections in up to 10 percent of patients with the acquired immunodeficiency syndrome (AIDS). Nearly 50 percent of AIDS patients with previously treated cryptococcal meningitis will experience a relapse within six months. To reduce the likelihood of relapse, a maintenance regimen of amphotericin B is often administered weekly. However, the drug's intravenous route of administration and considerable toxicity have led to a search for alternative antifungal agents. In this report, we document our experience with fluconazole, a new oral triazole antifungal agent. Twenty-two patients with AIDS and various forms of cryptococcosis were treated in an open-label study with 50 to 400 mg/day of fluconazole. The following laboratory studies were done on a monthly basis: complete blood cell count, liver function tests, serum creatinine level, serum cryptococcal antigen level, and serum fluconazole level. Lumbar puncture was performed in patients with meningitis every four to eight weeks to evaluate cerebrospinal fluid cryptococcal antigen, India ink preparation findings, fungal culture, fluconazole level, and protein, glucose, and cell count. Of seven patients with active culturepositive infections, four showed clinical and microbiologic responses (three of four with meningitis, one of three with extraneural cryptococcosis). Fifteen patients who had already undergone successful amphotericin B therapy for either meningitis (n = 14) or pneumonia (n = 1) received fluconazole as prophylaxis against relapse. Fourteen patients remained free of infection during 11 to 64 weeks of suppressive therapy; one patient with meningitis experienced relapse after 26 weeks of treatment. Adverse reactions were limited to increases in hepatic enzyme levels in four patients. These results appear sufficiently encouraging to warrant further trials of this oral agent in the suppression of chronic cryptococcosis and perhaps in the treatment of acute infection.