EVALUATION OF POSSIBLE CORRELATIONS BETWEEN ANTIFUNGAL SUSCEPTIBILITIES OF FILAMENTOUS FUNGI IN-VITRO AND ANTIFUNGAL TREATMENT OUTCOMES IN ANIMAL INFECTION MODELS

Nine isolates of filamentous fungi previously tested in 11 different l aboratories for their susceptibilities to amphotericin B and itraconaz ole in vitro were injected intravenously into mice and guinea pigs, an d responses to treatment with both agents were studied, The experiment s were done in a single laboratory, Mean survival times, the percentag es of animals surviving 12 days after infection, and culture results f or samples of deep organs obtained postmortem were used as markers of antifungal efficacy, Because of variations in organism pathogenicity, interpretable test systems in vivo could not be established for Fusari um spp, in mice or guinea pigs or for Pseudallescheria boydii in mice, even with the use of immunosuppressive pretreatments, Among the infec tions that could be evaluated, some degree of response to the correspo nding treatment in vivo was seen in animals infected with each of two Rhizopus arrhizus isolates susceptible to amphotericin B at < 0.5 mu g /ml and Aspergillus spp, isolates susceptible to itraconazole at < 1.0 mu g/ml. Conversely, no responses were apparent with infecting strain s for which MICs were greater than or equal to 2 mu g/ml (amphotericin B) or greater than or equal to 1 mu g/ml (itraconazole). However, the limitations of the intravenous challenge systems studied mean that no firm conclusion relating MICs in vitro to the lowest effective doses in vivo could be drawn.