The susceptibilities of 216 isolates of pathogenic and commensal yeasts to 5-fluorocytosine were tested by a disk diffusion technique with use of 1- and 10-microgram disks. Minimal inhibitory concentrations (MICs) were determined by an agar dilution procedure with yeast morphology agar, pH 5.0, supplemented with 0.25 mg of thiamine/dl. Zones of inhibition produced by the two disks were correlated with paired MIC values. An MIC of 16 micrograms/ml, the upper limit of probable clinical susceptibility, correlated with zones of 14 mm and 25 mm, respectively, for the 1- and 10-microgram disks. With these values as interpretative breakpoints, the 1-microgram disk would have failed to predict clinical susceptibility with 25% of the suceptible isolates of Candida species other than Candida albicans, with 14% of the susceptible isolates of Cryptococcus neoformans, with 7% of the susceptible isolates of C. albicans, and with one of the 25 susceptible isolates of Torulopsis glabrata. The 10-microgram disk would have failed to predict susceptibility with only two isolates of Candida species.

Ambruticin (W7783) was evaluated in vivo in mice subacutely or nonlethally infected with Histoplasma capsulatum. Results were compared with those obtained with amphotericin B, the drug of choice in human histoplasmosis. In one experiment, ambruticin was shown to be capable of curing infected animals as evidenced by totally negative liver and spleen cultures obtained when mice were sacrificed after 4 weeks of oral treatment with 150 mg of drug per kg per day. The 50% cure dose for ambruticin was between 75 and 150 mg/kg per day; the 50% cure dose for oral amphotericin B in this experiment was between 1.56 and 6.25 mg/kg per day. In a second experiment, both oral ambruticin (150 mg/kg per day) and oral amphotericin B (25 mg/kg per day) were again curative, but to a lesser degree than in the first experiment. Biological cures were obtained with both drugs after 3 and 4 weeks of treatment but not after 2 weeks.Ambruticin (W7883) has been shown to be a relatively broad-spectrum antifungal agent active in vitro against a variety of filamentous and dimorphic fungal pathogens (4-6). It already has been shown to be active in vivo in mice experimentally infected with Coccidioides immitis and, moreover, capable both of protecting experimental animals against infection with this organism and of producing biological cures (1, 2). The studies to be reported here compared the in vivo efficacy of orally administered ambruticin with that of orally administered amphotericin B in mice experimentally infected with Histoplasma capsulatium. Cultural studies. In both experiments, cultural studies were performed on target organs of surviving animals at the end of the treatment period. In these studies, spleens and livers were removed from sacrificed survivors, placed in 3-to 4-nil volumes of saline contained in plastic bags, and squashed to produce suspensions which were then plated on Mycosel agar (BBL) with added chloramphenicol. Approximately 1 ml, or 25% of each organ suspension, was plated. The inoculated plates were incubated at 28°C until sufficient growth was present to permit accurate mycological identification. Growth was scored on the basis of + (-10 colonies), ++ (10 to 100 colonies), and +++ to ++++ (greater than 100 colonies, or confluent growth with few or no discrete colonies). Identifications for at least one-third of all positive plates from each group of animals were confirmed by microscopic examination. MATERIALS AND METHODSIn the second experiment, 10 treated, infected mice from each of the two treatment regimen groups as well as the group of placebo-treated mice were sacrificed at the end of each week of treatment. One group of 10 infected but untreated mice was sacrificed on the first day of treatment. Livers and spleens were removed from these animals and processed as above for cultural studies.

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Antibiotic medium 20 FDA and antibiotic medium 3 FDA were compared to determine if antibiotic medium 3 would be suitable for in vitro susceptibility testing with amphotericin B.

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