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Pneumocystis carinii is resistant to imidazole antifungal agents
M S Bartlett1, S F Queener, M M Shaw
1Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis 46202-5120.
Abstract:
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.
Insights
Imidazole antifungal drugs are ineffective against Pneumocystis carinii pneumonia. This is because P. carinii lacks ergosterol, the primary target of these antifungal agents.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Pharmacology
Background:
- Pneumocystis carinii pneumonia (PCP) is a serious opportunistic infection.
- Given the fungal relationship of P. carinii, antifungal imidazole drugs were investigated for PCP treatment.
Purpose of the Study:
- To evaluate the efficacy of six imidazole antifungal drugs against P. carinii.
- To determine the mechanism behind the ineffectiveness of imidazoles against P. carinii.
Main Methods:
- In vitro screening of six imidazole drugs against P. carinii in short-term cultures.
- In vivo testing of imidazole drugs in infected rats.
- Analysis of P. carinii cell membranes for the presence of ergosterol.
Main Results:
- None of the tested imidazole drugs demonstrated significant efficacy in vivo in infected rats.
- Only miconazole exhibited minimal activity in vitro at a high concentration (10 µg/ml).
- Cell membrane analysis revealed the absence of ergosterol in P. carinii.
Conclusions:
- Imidazole antifungal drugs are not effective for treating P. carinii pneumonia.
- The absence of ergosterol in P. carinii explains the lack of response to imidazole therapy.