Evaluation of an experimental animal model for testing antifungal substances.

Accumulated evidence indicates that infection by fungi capable of causing systemic disease usually results in a relatively strong acquired resistance. The working hypothesis for this study was that an antifungal substance, even one with only slight fungistatic activity, could be an effective chemotherapeutic agent by arresting progression of the infection until acquired resistance became effective. The present study involved establishing and evaluating an experimental animal model (coccidioidomycosis in mice) which could be used to test this hypothesis. This model was reasonably similar to the natural disease. Results with infected nontreated animals indicated that the plot of mortality frequency against survival time did not follow a normal distribution curve. Thus, nonparametric procedures were used for evaluation. Use of this model with an established antibiotic (amphotericin B), with a crude preparation of a new antibiotic (CB-310), and with synthetic organoselenium compounds demonstrated that even low levels of antifungal activity could be detected. The model should be useful not only to test the original hypothesis but also to screen antifungal substances for their potential as chemotherapeutic agents.