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Antimicrobial Agents and Chemotherapy, July 2000, p. 1850-1854, Vol. 44, No. 7
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Comparison of the Echinocandin Caspofungin with Amphotericin B for Treatment of Histoplasmosis following Pulmonary Challenge in a Murine Model

Steve Kohler,1,2 L. Joseph Wheat,1,2,3,4,* Patricia Connolly,2,3 Carol Schnizlein-Bick,3 Michelle Durkin,2,3 Melinda Smedema,2,3 Janet Goldberg,2,3 and Edward Brizendine3

Department of Veterans' Affairs Hospital,1 Departments of Medicine,3 and Pathology,4 Indiana University School of Medicine, and Histoplasmosis Reference Laboratory,2 Indianapolis, Indiana

Received 30 December 1999/Returned for modification 9 February 2000/Accepted 29 March 2000

Twenty clinical isolates of Histoplasma capsulatum were tested for their in vitro susceptibilities to caspofungin in comparison to those to amphotericin B by following National Committee for Clinical Laboratory Standards guidelines for yeasts. The mean MICs were 16.6 µg/ml (range, 8 to 32 µg/ml) for caspofungin and 0.56 µg/ml (range, 0.5 to 1.0 µg/ml) for amphotericin B. Survival experiments used a 105 dose in a pulmonary challenge model with B6C3F1 mice. All mice that received amphotericin B at 2 mg/kg of body weight every other day (q.o.d.), 30% of mice that received caspofungin at 8 mg/kg/day, and 20% of mice that received caspofungin at 4 mg/kg/day survived to day 15, while mice that received caspofungin at 2 mg/kg/day and all control mice that received the vehicle died by day 14. Amphotericin B at 2 mg/kg q.o.d. markedly reduced the fungal burden in the lungs and spleens, as measured by Histoplasma antigen detection techniques and quantitative cultures, for each comparison. Caspofungin at 10 mg/kg twice a day (b.i.d.) did not reduce the fungal burden, as measured by antigen detection techniques, but slightly reduced the levels of fungi in both the lungs and spleens, as determined by quantitative cultures. Caspofungin at 5 mg/kg b.i.d. did not affect fungal burden. Overall, caspofungin had only a slight effect on survival or fungal burden.

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

Antimicrobial Agents and Chemotherapy, July 2000, p. 1850-1854, Vol. 44, No. 7
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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