Activity of two polyene and two imidazole antimicrobics on Candida albicans in human fibrin clots
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Abstract:
The vegetations of infective fungal endocarditis were simulated by preparing human fibrin clots containing 10(5) CFU of Candida albicans per clot. Clots were incubated in human serum without drugs (controls) or with equimolar concentrations (2.5 to 20 nmol/ml) of four antifungal antimicrobics: AMB and miconazole (both colloidal suspensions) and DAB and KET (both molecularly dispersed). Over a period of 4 days of incubation, clots were resuspended in freshly prepared serum-antimicrobic every 12 hr. Cohorts of control and drug-exposed clots were cultured quantitatively at 24 hr intervals. Neither imidazole at any concentration tested prevented growth of C. albicans to an extent that was significantly different from growth in the control clots. Both polyenes reduced the CFU/clot, with AMB significantly more active than DAB.
Insights
Antifungal drugs were tested against Candida albicans in simulated infective fungal endocarditis. Amphotericin B (AMB) and dAb showed antifungal activity, while imidazoles were ineffective.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Infective fungal endocarditis is a severe condition often caused by Candida species.
- Fungal vegetations on heart valves pose a significant treatment challenge.
- Evaluating antifungal efficacy within a simulated vegetation model is crucial.
Purpose of the Study:
- To assess the in vitro efficacy of four antifungal agents against Candida albicans within simulated human fibrin clots.
- To compare the activity of polyenes (Amphotericin B, dAb) and imidazoles (miconazole, ketoconazole) in this model.
Main Methods:
- Human fibrin clots inoculated with Candida albicans (10^5 CFU/clot) were prepared.
- Clots were incubated in human serum with varying concentrations of Amphotericin B, dAb, miconazole, or ketoconazole for 4 days.
- Clots were serially transferred to fresh drug-containing serum every 12 hours.
- Quantitative cultures were performed every 24 hours to determine Colony Forming Units (CFU/clot).
Main Results:
- Imidazole antifungals (miconazole, ketoconazole) did not significantly inhibit Candida albicans growth compared to controls.
- Both polyene antifungals, Amphotericin B (AMB) and dAb, reduced CFU/clot.
- Amphotericin B demonstrated significantly greater antifungal activity than dAb in this model.
Conclusions:
- Polyene antifungals are more effective than imidazoles against Candida albicans in a simulated fungal endocarditis vegetation model.
- Amphotericin B exhibits superior efficacy compared to dAb in reducing fungal burden within the simulated vegetations.