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Uniform susceptibility of various strains of Coccidioides immitis to amphotericin B
Abstract:
The susceptibility of 12 strains of Coccidioides immitis to amphotericin B (amB) was studied in vitro and in vivo. The minimal inhibitory concentration (MIC) of the mycelial phase of these strains was 0.078 to 0.16 mug/ml after 3 days of incubation, but by 15 days all strains were inhibited by 2.5 mug/ml. Mice infected intraperitoneally with these strains were sucessfully treated with 0.5 mg of amB per kg per day. These strains included several studied by others and which reportedly varied widely in susceptibility (MIC from 0.24 to 24.01 mug/ml) to amB. Four of these strains representing this putative broad range of susceptibility were used to infect mice intranasally. Regardless of infecting strain, mice were sucessfully treated with 0.38, 0.75, and 1.5 mg/kg, but 0.19 mg/kg was only partially effective. Thus, in vivo as well as in vitro there was a uniform response of C. immitis strains to amB.
Insights
This study investigated Coccidioides immitis susceptibility to amphotericin B (amB). All tested strains showed a uniform response to amB in vitro and in vivo, indicating consistent treatment efficacy for coccidioidomycosis.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Coccidioides immitis is a fungal pathogen causing coccidioidomycosis.
- Antifungal susceptibility testing is crucial for effective treatment.
- Previous studies suggested variable susceptibility of C. immitis to amphotericin B (amB).
Purpose of the Study:
- To evaluate the in vitro and in vivo susceptibility of multiple C. immitis strains to amphotericin B.
- To determine if C. immitis strains exhibit uniform or variable responses to amB.
- To inform treatment strategies for coccidioidomycosis.
Main Methods:
- In vitro antifungal susceptibility testing using minimal inhibitory concentration (MIC) assays.
- In vivo efficacy studies in murine models of coccidioidomycosis (intraperitoneal and intranasal infection).
- Testing of 12 distinct C. immitis strains with varying reported susceptibilities.
Main Results:
- In vitro, all 12 C. immitis strains showed consistent inhibition by amB, with MICs ranging from 0.078 to 2.5 mug/ml over 15 days.
- In vivo, mice infected with amB-susceptible and -resistant strains responded uniformly to amB treatment.
- Therapeutic success was achieved with amB doses of 0.38 mg/kg and higher in intranasal infection models.
Conclusions:
- Coccidioides immitis strains demonstrate a uniform susceptibility profile to amphotericin B.
- Amphotericin B is consistently effective against various C. immitis strains in both laboratory and animal models.
- These findings support the reliable use of amB for treating coccidioidomycosis regardless of isolate source.