RESPONSE TO ANTIFUNGAL THERAPY BY HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS WITH DISSEMINATED PENICILLIUM-MARNEFFEI INFECTIONS AND IN-VITRO SUSCEPTIBILITIES OF ISOLATES FROM CLINICAL SPECIMENS

Eighty-six patients with laboratory evidence of human immunodeficiency virus infection presented to Chiang Mai University Hospital in Chiang Mai, Thailand, between 1 June 1990 and 30 June 1992 with systemic inf ection caused by the dimorphic fungus Penicillium marneffei. Thirty is olates of P. mameffei from clinical specimens from these patients were tested for their in vitro susceptibilities to amphotericin B, 5-fluor ocytosine, miconazole, ketoconazole, itraconazole, and fluconazole. P. marneffei was highly susceptible to miconazole, itraconazole, ketocon azole, and 5-fluorocytosine. Amphotericin B showed intermediate antifu ngal activity, while fluconazole was the least active; some strains of the fungus were resistant to fluconazole. The clinical and microbiolo gical responses correlated with the overall patterns of in vitro susce ptibility to the azoles, whereas results with amphotericin B were more difficult to assess. Antibiotic failures of initial therapy occurred in 8 of 35 (22.8%) patients treated with amphotericin B, 3 of 12 (25%) patients treated with itraconazole, and 7 of 11 (63.6%) patients trea ted with fluconazole. Itraconazole or ketoconazole should be considere d to be the drug of first choice in the treatment of mild to moderatel y severe P. marneffei infection. Parenteral therapy with amphotericin B may be required for seriously ill patients. Since at least 12 patien ts who responded to initial therapy relapsed within 6 months regardles s of initial antifungal therapy, maintenance oral therapy with itracon azole or ketoconazole may be necessary.