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Antimicrob Agents Chemother. 1976 August; 10(2): 318-321
Copyright © 1976 American Society for Microbiology. All Rights Reserved.

Treatment of Murine Coccidioidomycosis with Polymyxin B

¹ Department of Medical Microbiology, School of Medicine, University of California, Davis, California 95616

ABSTRACT

An agar dilution method was employed to test the susceptibility of 12 strains of Coccidioides immitis to polymyxin B (PB). After 3 days of incubation, eight strains were markedly inhibited by 5.0 µg of PB per ml and four strains did not grow. PB at 10 µg/ml inhibited the growth of all strains through 20 days of incubation. To determine whether PB has anticoccidioidal activity in vivo, mice in groups of 30 were infected intraperitoneally with a mean lethal dose (LD₅₀) or 20 LD₅₀ of arthrospores of C. immitis ATCC 28868 (Silveira). Treatment by intraperitoneal injection of PB (2.5 mg/kg) was begun 2 or 5 days after challenge. By 40 days after infection, 47 and 7% of the untreated mice challenged with an LD₅₀, respectively, were alive. Of mice infected with an LD₅₀ or 20 LD₅₀ and treated with PB beginning 2 days after the challenge, 90% of each group were alive by day 40. Initiation of PB therapy 5 days after infection permitted survival of 84% of the mice infected with an LD₅₀; however, only 27% of the mice infected with 20 LD₅₀ survived by day 40. In this latter group there was evidence that PB prolonged life since 56% of the treated mice were alive by day 15 as compared with 30% of the controls. PB in vivo was fungistatic since the majority of treated mice had C. immitis in the liver, lungs, and spleen.