In vitro and in vivo activities of Sch 39304, fluconazole, and amphotericin B against Histoplasma capsulatum.
The antifungal activities of amphotericin B and two triazoles, Sch 39304 and fluconazole, were tested against Histoplasma capsulatum. In this study Sch 39304 compared favorably with amphotericin B in treating histoplasmosis in normal and leukopenic mice, whereas fluconazole was much less active. The differences in the efficacies of the triazoles appeared to be due to differences in their pharmacokinetics and the dosage schedule that was used. For amphotericin B there was a good correlation between in vitro and in vivo efficacy, but this was not true of the triazole derivatives. These results further demonstrate that, with the methods used in this study, in vitro susceptibility testing of triazoles may not be predictive of in vivo activity against isolates of H. capsulatum.
Kobayashi
G S
GS
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Travis
S J
SJ
Rinaldi
M G
MG
Medoff
G
G
D000666:Amphotericin B / Q000097:blood / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D015725:Fluconazole / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006658:Histoplasma / Q000187:drug effects; D006660:Histoplasmosis / Q000150:complications / Q000188:drug therapy*; D007970:Leukopenia / Q000150:complications; D051379:Mice; D008826:Microbial Sensitivity Tests; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use
D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304; D000666:Amphotericin B; D015725:Fluconazole