Inhibition of Coccidioides immitis in vitro and enhancement of anticoccidioidal effects of amphotericin B by polymyxin B

Growth of the spherule phase of Coccidioides immitis in liquid glucose mineral salts medium was suppressed for 13 days by 5 to 10 μg of polymyxin B per ml. Inhibition of growth was also noted when filter paper disks containing polymyxin B were placed on the surface of arthrospore seeded defined medium solidified with refined agar. The antibiotic evidently damaged the cytoplasmic membrane inasmuch as spherules suspended in distilled water containing 10 μg of polymyxin B per ml rapidly lost nucleotides. Leakage of nucleotides was prevented by 0.1 M Ca²⁺. The anticoccidioidal activity of amphotericin B (0.02 to 0.08 μg/ml) was enhanced by 2.5 μg of polymyxin B per ml. Colistin (polymyxin E) methanesulfonate did not inhibit spherule growth at concentrations as high as 50 μg/ml. This may be because colistin, though structurally similar to polymyxin B, is not cationic because its γ amino groups are masked by methanesulfonate radicals.