Effects of Sublethal Concentrations of Amphotericin B on Candida albicans

Abstract
Because sublethal concentrations of antibiotics can have important effects on bacteria and may aid host defenses, even in the absence of direct microbial killing, the effect of brief sublethal exposures to amphotericin B on Candida albicans blastoconidia was evaluated. Amphotericin B (0.01–1.0 μg/ml for 60 min) inhibited germ tube formation and yeast adherence to both serum-coated plastic surfaces and fibrin matrices. These effects were not reversed by cation (K+ or Mg++ supplementation. Amphotericin B pretreatment accelerated clearance of C. albicans from the peritoneal surfaces of mice and reduced the inflammatory stimulus associated with this clearance, at least as measured by neutrophil influx. However, pretreatment did not facilitate killing of C. albicans by either neutrophils or monocytes in vitro. Thus sublethal concentrations of amphotericin B inhibit two activities of C. albicans that probably contribute to surface colonization and tissue invasion. These results provide one explanation for the clinical benefits observed with short courses of amphotericin B therapy for surface-limited candidal infections (e.g., esophagitis).