Pneumocystis carinii is resistant to imidazole antifungal agents.
Because Pneumocystis carinii is closely related to fungi, drugs useful for treating mycoses have been considered for use in the treatment of P. carinii pneumonia. Six antifungal imidazole drugs were tested for their activities against P. carinii in a short-term culture screen and in animals. None of the imidazoles tested was effective in inoculated infected rats, and only miconazole showed slight effects in culture at the high concentration of 10 micrograms/ml. Analysis of cell membranes from culture-grown P. carinii showed that ergosterol, the target for this class of antifungal agents, was absent, so that the lack of effect of these agents is rational.
Bartlett
M S
MS
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis 46202-5120.
Queener
S F
SF
Shaw
M M
MM
Richardson
J D
JD
Smith
J W
JW
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D004875:Ergosterol / Q000032:analysis; D005260:Female; D015725:Fluconazole / Q000494:pharmacology; D008401:Gas Chromatography-Mass Spectrometry; D017964:Itraconazole / Q000494:pharmacology; D007654:Ketoconazole / Q000494:pharmacology; D008825:Miconazole / Q000494:pharmacology; D011010:Pneumocystis / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014230:Triazoles / Q000494:pharmacology
D000935:Antifungal Agents; D014230:Triazoles; C056513:Sch 39304; D017964:Itraconazole; D008825:Miconazole; D015725:Fluconazole; D007654:Ketoconazole; D004875:Ergosterol