Obfuscation of the Activity of Antifungal Antimicrobics by Culture Media

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Abstract
The potential of six culture media in current use for antagonism of the antifungal activity of amphotericin B, 5-fluorocytosine, and clotrimazole was assessed by comparison with a totally defined, nutritionally adequate, well-buffered, synthetic amino-acid medium, SAAMF. Of the six conventional media, only one was a synthetic formulation; although it was nutritionally adequate, it was essentially unbuffered. The remaining five media were complex, undefined, and undefinable. All five undefined media were nutritionally adequate, two were modestly well buffered, but all nullified the activity of one or more of the three antimicrobics studied. The obfuscatory capacity of each medium was quantitated by determination of the absolute minimal inhibitory concentration (M'IC) of each antimicrobic for a strain of Candida albicans. With 5-fluorocytosine and clotrimazole, but not with amphotericin B, there was significant increase in M'IC values as incubation was continued. By adding (individually) pyrimidines and pyrimidine ribosides to SAAMF, it was shown that cytosine and uridine blocked expression of the anticandidal activity of 5-fluorocytosine. Meaningful data cannot be obtained from susceptibility testing of fungi in vitro unless the potential for interaction between antimicrobic and culture medium is recognized and compensated for, most expeditiously, through use of a totally defined culture medium.

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