The Evaluation of Nystatin on the Course of Coccidioidomycosis in Mice

Abstract

Nystatin (Fungicidin) was first isolated and reported in 1949 by Brown and Hazen (1) and they have presented its chemical, biological and fungicidal properties in several subsequent articles (2—4). It is obtained from an unidentified species of Streptomyces which in their collection was designated as strain No. 48240. The source of the drug is unique in that it is obtained from the pellicle formed by the growth of the organism in liquid medium and not from the culture filtrate. The known physical, chemical and biological properties of Nystatin distinguish it from any of the antibiotics reported in the literature. However, Raubitacheck, et al. (5), has recently isolated an antifungal antibiotic from the culture filtrate of a strain closely related to Streptomyces aureus which was found to be similar to Nystatin. Nystatin in amounts of 1.56 to 6.25 g/ml of broth was found in vitro to effectively inhibit the growth of a large variety of nonpathogenic and pathogenic fungi including Coccidioides immitis. The agent has not shown activity in concentrations as high as 100 g/ml. against some of the common bacterial pathogens. The incubation of Nystatin in the presence of defibrinated horse blood or serum does not modify its activity. The approximate LD50 of crude Nystatin when administered intraperitoneally to mice was between 20 and 26 mg/kg. Mice injected with large numbers of Cryptococcus neoformans and Histo plasma capsulatum and given repeated parenteral doses of Nystatin had a milder form of infection and their life was prolonged beyond that of the controls. The purpose of this paper is to present the preliminary results obtained from an evaluation of Nystatin both in vitro and in vivo against Coccidioides immitis.