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Antimicrobial Agents and Chemotherapy, September 1999, p. 2165-2169, Vol. 43, No. 9
0066-4804/99/$04.00+0

Effects of the Hematoregulatory Peptide SK&F 107647 Alone and in Combination with Amphotericin B against Disseminated Candidiasis in Persistently Neutropenic Rabbits

Caron A. Lyman,1,* Corina Gonzalez,1 Mark Schneider,2 James Lee,1 and Thomas J. Walsh1

Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland 20892,1 and Department of Molecular Virology and Host Defense, SmithKline Beecham, Collegeville, Pennsylvania 194262

Received 4 January 1999/Returned for modification 1 March 1999/Accepted 29 June 1999

The effects of the hematoregulatory peptide SK&F 107647 were examined in a persistently and profoundly neutropenic rabbit model of disseminated candidiasis in order to determine its potential to enhance resistance against infection and its role as an adjunct to conventional antifungal chemotherapy. In healthy animals, SK&F 107647 elicited a time-dependent increase in CD11b-positive monocytes and neutrophils. When administered to neutropenic rabbits infected with Candida albicans, no significant differences in the number of CFU per gram in any of the tissues tested compared with the number in untreated control rabbits were detected. However, when SK&F 107647 was administered in combination with low doses of amphotericin B, there was a significant reduction in organism burden in the lungs, liver, spleen, and kidneys compared with the burdens in the organs of untreated control animals and in the lungs and kidneys compared with the burdens in the lungs and kidneys of animals treated with amphotericin B alone. These data suggest a potential role for this peptide as adjunctive therapy in combination with conventional antifungal agents in the treatment of disseminated candidiasis in the setting of profound and persistent neutropenia.

* Corresponding author. Mailing address: Immunocompromised Host Section, Pediatric Oncology Branch, National Cancer Institute, Building 10, Room 13N240, Bethesda, MD 20892. Phone: (301) 496-8061. Fax: (301) 402-0575. E-mail: lymanc{at}mail.nih.gov.

Antimicrobial Agents and Chemotherapy, September 1999, p. 2165-2169, Vol. 43, No. 9
0066-4804/99/$04.00+0




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