Comparative efficacy of forphenicinol, cyclosporine, and amphotericin B in experimental murine coccidioidomycosis

Cohorts of ten mice, uninfected and infected (intratracheal injection of coccidioidal arthroconidia), were treated for 23 days by intravenous injections of either 5% glucose solution, an immunostimulant (forphenicinol), an immunodepressant (cyclosporine), or amphotericin B. All mice were autopsied (survivors at 26 days postinoculation) and suspensions of lungs, livers, and spleens were cultured. All uninfected animals survived and gained weight, whereas, only 20% of the infected controls survived, and all lost weight. Treatment with forphenicinol had no effect on survival or weight. Cyclosporine secured 90% survival at the lowest dose and 60% at the higher doses, with no net loss of weight; however, all cultures of organs yielded heavy growth of Coccidioides immitis . With amphotericin B, all mice survived and gained weight; four mice from each of the two treatment groups yielded modest growth of C . immitis from the lungs, and one mouse of each group yielded sparse growth from liver and spleen. The paradox of no effect from an immunostimulant and therapeutic effect from an immunodepressant correlated with susceptibility testing of C . immitis in vitro.