title: Combination therapy with fluconazole and flucytosine for pulmonary cryptococcosis.
abstract: We investigated, in vitro, the combined effects of fluconazole (FLCZ) and flucytosine (5-FC) against different strains of Cryptococcus neoformans, and retrospectively analyzed the clinical efficacy of combination therapy of FLCZ and 5-FC in patients with pulmonary cryptococcosis. The minimum inhibitory concentrations (MICs) of antifungal agents and drug interaction were determined by the broth microdilution method and checkerboard titration. FLCZ and 5-FC showed synergistic activity against 8 (32%) of 25 strains of C. neoformans. The clinical efficacy of the 2 drugs when combined together was good in 9 (90%) patients and fair in 1 (10%) patient with pulmonary cryptococcosis. Renal dysfunction occurred in 1 patient. Our results suggest that a combination therapy using FLCZ and 5-FC is clinically useful in patients with pulmonary cryptococcosis who otherwise show a limited response to monotherapy.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: S
authors.initials: S
authors.lastname: Maesaki
authors.forename: H
authors.initials: H
authors.lastname: Kakeya
authors.forename: K
authors.initials: K
authors.lastname: Yanagihara
authors.forename: H
authors.initials: H
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hirakata
authors.forename: K
authors.initials: K
authors.lastname: Tomono
authors.forename: T
authors.initials: T
authors.lastname: Tashiro
authors.forename: S
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage*; D003453:Cryptococcosis / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage*; D005437:Flucytosine / Q000008:administration & dosage*; D006801:Humans; D008172:Lung Diseases, Fungal / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000935:Antifungal Agents; D015725:Fluconazole; D005437:Flucytosine