Antifungal activity of miconazole against recent clinical isolates of Candida spp., as determined by minimum inhibitory concentration

Abstract number: 1733_1477

Ghannoum M.A.

Objectives: Miconazole (MICON) has long been used for the topical treatment of Candidavaginitis and other fungal infections of the skin. As such, existing susceptibility data for MICON is quite old and was generated before standard methodology was established. Currently there is an increased incidence of oropharyngeal candidiasis among immunocompromised patients, especially in the HIV positive population, for which a new delivery system of MICON has been developed. With Miconazole Lauriad^® tablets currently in Phase III clinical trials, it is important to establish a susceptibility profile for MICON against recent clinical Candida isolates using standard methodology. The objective of this study was to test MICON against a large number of Candida isolates to determine whether there has been any development of resistance to this antifungal in the patient population. The antifungal activity of MICON, as determined by minimum inhibitory concentration (MIC) was compared to amphotericin B (AM), caspofungin (CAS), clotrimazole (CLOT), fluconazole (FLU), itraconazole (ITRA), nystatin (NYS), and voriconazole (VOR).

Methods: MICs were determined according to CLSI M27A2. Inhibition endpoints were read as a 50% reduction in growth compared to the growth control after 24 hours incubation (AM was read at 100% inhibition).

Results: MICON demonstrated potent inhibitory activity against all of the Candida strains tested. The overall MIC range for MICON was 0.004–1.0 mg/mL, while the MIC₅₀ and MIC₉₀, defined as the minimum concentration that inhibited 50% and 90% of isolates tested, were 0.06 and 0.5 mg/mL, respectively. With the exception of FLU, all of the comparator drugs demonstrated activity against the panel of test isolates. The MICON MIC₉₀ for all species was comparable to that of AM, CAS, CLOT, ITRA, NYS, and VOR (within three dilutions), and was four dilutions lower than FLU. Importantly, MICON demonstrated MICs three to eight fold lower than FLU against FLU-resistant strains.

Conclusion: Our data showed that MICON demonstrated potent inhibitory activity against all of the Candida isolates tested, including those with known FLU resistance. This indicates that recent clinical isolates remain susceptible to this antifungal and do not reflect increased resistance. This has important implications to the new application of MICON in the treatment of oropharyngeal candidiasis.