Journal Article

Emergence of Resistance to Fluconazole as a Cause of Failure during Treatment of Histoplasmosis in Patients with Acquired Immunodeficiency Disease Syndrome

L. Joseph Wheat, Patricia Connolly, Melinda Smedema, Edward Brizendine and Richard Hafner

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 33, issue 11, pages 1910-1913
Published in print December 2001 | ISSN: 1058-4838
Published online December 2001 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/323781
Emergence of Resistance to Fluconazole as a Cause of Failure during Treatment of Histoplasmosis in Patients with Acquired Immunodeficiency Disease Syndrome

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In sequential clinical trials of treatment for histoplasmosis in patients with acquired immunodeficiency syndrome, therapy with fluconazole failed in a higher proportion of patients than did therapy with itraconazole. To determine the cause for failure with fluconazole, antifungal susceptibility testing that used modified National Committee on Clinical Laboratory Standards procedures was performed on all baseline and failure isolates. Failure occurred more frequently in patients with baseline isolates with fluconazole minimum inhibitory concentrations (MICs) ≥5 μg/mL versus lower MICs; 29% versus 3%, respectively. There was at least a 4-fold increase in fluconazole MIC in the isolates from 10 (59%) of 17 patients for whom paired pretreatment and failure or relapse isolates were available. Cross-resistance to itraconazole was not seen. In conclusion, fluconazole is less active than itraconazole for Histoplasma capsulatum and induces resistance during therapy, which accounted for treatment failure in some patients.

Journal Article.  2324 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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