Evaluation of the anticryptococcal activity of the antibiotic polymyxin B in vitro and in vivo

Polymyxin B (PMB), a cationic lipid oligopeptide used to treat Gram-negative bacterial infections, was previously identified to possess broad-spectrum antifungal activity and to work synergistically with azole antifungals in vitro. Here we evaluated the efficacy of PMB against Cryptococcus neoformans in vitro and in vivo and explored the mechanism of the hypersensitivity of this fungus to this compound. Using comparative time-course assays, PMB was found to kill both proliferative and quiescent cryptococcal cells in vitro. Presence of the polysaccharide capsule, a characteristic feature of Cryptococcus, significantly enhances the susceptibility of this fungus to the fungicidal activity of PMB. Furthermore, PMB is able to reduce the tissue fungal burden both in intravenous and inhalation models of murine cryptococcosis at a level comparable with the commonly used antifungal fluconazole. These findings suggest that PMB could provide an additional option for treatment against systemic cryptococcosis.