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Antimicrobial Agents and Chemotherapy, January 2002, p. 248-250, Vol. 46, No. 1
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.1.248-250.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Antigen Clearance during Treatment of Disseminated Histoplasmosis with Itraconazole versus Fluconazole in Patients with AIDS

L. Joseph Wheat,1,2,3,{ddagger}* Patricia Connolly,1,3 Nicholas Haddad,3,{dagger} Ann Le Monte,1,3 Edward Brizendine,3 and Richard Hafner4,{ddagger}

Histoplasmosis Reference Laboratory,1 Veterans’ Affairs Medical Cente, Indianapolis, Indiana,2 Indiana University School of Medicine,3 Indiana Division of AIDS, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, Maryland4

Received 25 July 2001/ Returned for modification 17 September 2001/ Accepted 10 October 2001

Antifungal treatment reduces the concentration of Histoplasma antigen in blood and urine, supporting a hypothesis that antigen clearance could be used to compare the activity of new agents for treating histoplasmosis. In separate trials in patients with AIDS, clinical response was similar with itraconazole (85%) and fluconazole (74%). Fungal blood cultures at week 4, however, were negative in a significantly higher proportion of patients treated with itraconazole (92.3%) than in those treated with fluconazole (61.9%) (P = 0.017). Baseline antigen concentrations were similar in the two groups: serum, P = 0.7235; and urine, P = 0.1360. After 4 weeks of treatment, the decline in antigen from baseline in serum was similar in the two treatment groups (P = 0.5237), as it was in urine (P = 0.4679). At week 12, the decline in antigen from baseline in serum also was similar in the two groups (P = 0.4911) and in urine (P = 0.2786). More rapid clearance of fungemia suggests that itraconazole is more effective than fluconazole in treating histoplasmosis. This study demonstrates that clearance of fungemia is a better measure of antifungal effect than clearance of antigen.

* Corresponding author. Mailing address: Indiana University School of Medicine, Histoplasmosis Reference Laboratory, 1001 West Tenth St., OPW 430, Indianapolis, IN 46202-2879. Phone: (317) 630-6262. Fax: (317) 630-7522. E-mail: lwheat{at}iupui.edu.

{ddagger} Member of the AIDS Clinical Trials Group and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases.

{dagger} Present address: Washington University School of Medicine, St. Louis, Mo.

Antimicrobial Agents and Chemotherapy, January 2002, p. 248-250, Vol. 46, No. 1
0066-4804/01/$04.00+0     DOI: 10.1128/AAC.46.1.248-250.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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