Therapeutic Properties of Oral Ambruticin (W7783) in Experimental Pulmonary Coccidioidomycosis of Mice

Oral administration of ambruticin (W7783) (by gavage) was lifesaving in mice infected intranasally with arthrospores of Coccidioides immitis. Doses of 25 and 50 mg/kg of body weight, given twice daily by different schedules for from 17 to 60 days, eradicated the fungus from 71 to 100 percent of the infected mice. Lower doses (5 or 10 mg/kg once or twice daily by an intermittent 50-day regimen) prevented death in all instances but produced many fewer biologic cures. The animals tolerated all these doses well but were adversely affected by doses of 200 mg/kg given daily. Resistance to the drug was not induced by prolonged treatment Dose-related fungicidal and fungistatic properties in vitro correlated with doses that were life-sustaining or curative (or both) in vivo.