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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| Abstract |
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) > or =5 microg/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.
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| Authors | L J Wheat, P Connolly, M Smedema, E Brizendine, R Hafner, AIDS Clinical Trials Group and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases |
| Journal | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 33 Issue 11 Pg. 1910-3 (Dec 01 2001) ISSN: 1537-6591 [Electronic] United States |
| PMID | 11692303 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.) |
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