Inhibition of Coccidioides immitis In Vitro and Enhancement of Anticoccidioidal Effects of Amphotericin B by Polymyxin B

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Abstract
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 Ca 2+ . 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.