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

Abstract

Growth of the spherule phase of Coccidioides immitis in liquid glucose-mineral salts medium was suppressed for 13 days by 5 to 10 mug 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 mug 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 mug/ml) was enhanced by 2.5 mug of polymyxin B per ml. Colistin (polymyxin E) methanesulfonate did not inhibit spherule growth at concentrations as high as 50 mug/ml. This may be because colistin, though structurally similar to polymyxin B, is not cationic because its gamma-amino groups are masked by methanesulfonate radicals.