Relationship Between Antifungal Resistance and Switching in Candida Albicans Isolates

Candida albicans is the causative agent of oropharyngeal candidiasis, the most common oral complication in HIV/AIDS patients. As the use of antifungals increases in response to the large number of infections caused by C. albicans in AIDS patients, yeast isolates that are resistant in vitro and in vivo to fluconazole and Amphotericin B have emerged. C. albicans is capable of high-frequency, phenotypic switching, distinguishable by colony morphology. There is evidence to suggest that this phenotypic switching may play a role in antifungal resistance. This resistance can hold serious clinical consequences if a resistant organism spreads among a particular immunocompromised cohort of patients such as HIV/AIDS children in an orphanage. Objectives: The purpose of this study was to determine whether the observed phenotypic switching is related to antifungal resistance. Methods: Ninety-one oral C. albicans isolates collected from HIV/AIDS children residing in orphanages in Gauteng and a hospital out-patient clinic were screened for phenotypic switching. Forty(44%) of those isolates exhibited switching characteristics, and were selected for antifungal resistance testing against amphotericin B and fluconazole utilizing the E-test method. Results: Of the 40 switched isolates, 3 (7.5%) were found to be resistant to fluconazole with a MIC of >64µg/ml. Of these 3 isolates, 2(67%) were from children residing in orphanages, and 1(33%) was from the out-patient clinic. In addition, 1 (2.5%) was found to be resistant to amphotericin B with a MIC >1µg/ml, and was from the out-patient clinic. The remaining 36(90%) isolates were found to be sensitive to both amphotericin B and fluconazole. Forty-four percent (44%) of oral C. albicans isolates revealed phenotypic switching and 7.5% of the switched isolates exhibited resistance to fluconazole, while 2.5% exhibited resistance to amphotericin B. Conclusions: The switching-related fluconazole resistance is of concern because of the confined cohort of immunocompromised children in which it occurred.