Rapid fungicidal action of tioconazole and miconazole
Sir, Recent studies in our laboratory clearly showed that 4 โข 10 -5 M tioconazole or miconazole (i.e. 15-16/xg/ml) caused rapid 2-to 3-log reductions in colony forming units (CFU)/ml when added to early logarithmic phase yeast cultures of Candida albicans or Candida parapsilosis growing at 37 ~ with aeration (1, 2). In a more recent report concerned with effects of antifungal azoles on the ATP content of C albicans, Odds, Cheesman & Abbott (3) incidentally mentioned that they were unable to demonstrate the lethal action observed in our experiments. More specifically, it was stated that: 'in our hands neither miconazole nor tioconazole caused the rapid diminution of viable counts described by Beggs, even with exponential-phase yeast cells (E C. Odds & A. B. Abbott, unpublished results)'. Here I wish to provide the most probable explanation of this apparent discrepancy.
In our azole drug studies we routinely use a pH 7.0 liquid medium containing yeast nitrogen base, Lasparagine, and glucose (1). After dissolving these three major components in deionized water, the broth is adjusted from pH 5.3 to pH 7.0 with 2 N NaOH and filter sterilized. Cultures are incubated at 37 ~ with shaking at 150 rpm. Details of the unpublished viability studies mentioned by Odds et al. (3) were not given, but in the methods section they stated: 'Yeast-form cells were grown in a broth containing Mycological peptone (Oxoid), 10 g 1-1 and glucose, 40 g 1.2 shaken at 160 rpm and 37~ in air'. The pH of this mycological peptone medium was not stated, but in company literature prepared in England and obtained from Oxoid U.S.A. Inc. (Columbia, Maryland) a dilute solution of the peptone is reported to be at pH 5.4. Details of the viable count time-kill type of experiment presented in Fig. 1 were outlined in our earlier report (1). Data graphically summarized in Fig. 1 clearly show that the fungicidal action of tioconazole against C albicans that occurred in pH 7.0 medium did not occur when the same medium was used at pH 5.5. We recently have made similar observations with miconazole and have confirmed the findings with another strain of C albicans (i.e. ATCC 26790). Thus, the rapid fungicidal action of tioconazole, miconazole, and probably certain other azoles appears to be a highly pH-dependent phenomenon that does not occur under even moderately acidic conditions.