Emergence of fluconazole-resistant strains of Candida albicans in patients with recurrent oropharyngeal candidosis and human immunodeficiency virus infection

Abstract

After repeated use of fluconazole for therapy of oropharyngeal candidosis, the emergence of in vitro fluconazole-resistant Candida albicans isolates (MIC, 2 25 ,ig/ml) together with oral candidosis unresponsive to oral dosages of up to 400 mg of fluconazole were observed in patients with human immunodeficiency virus (H1V) infection. Antifungal susceptibility testing was done by broth microdilution and agar dilution techniques on C. albicans isolates recovered from a cohort of patients with symptomatic HIV infection who were treated repeatedly with fluconazole for oropharyngeal candidosis. In vitro findings did show a gradual increase in the MICs for C. albicans isolates recovered from selected patients with repeated episodes of oropharyngeal candidosis. Primary resistance of C. albicans to fluconazole was not seen. Cross-resistance in vitro occurred between fluconazole and other azoles (ketoconazole, itraconazole), but to a lesser extent. The results of the study suggest that the development of clinical resistance to fluconazole could be clearly correlated to in vitro resistance to fluconazole. Itraconazole may still serve as an effective antifungal agent in patients with HIV infection and oropharyngeal candidosis nonresponsive to fluconazole.

Synergistic mechanisms of retigeric acid B and azoles against Candida albicans

“…Candida albicans and other Candida species are common pathogens that frequently cause infection of skin, oral cavity and oesophagus, gastrointestinal tract, vagina and vascular system of humans (Calderone and Fonzi 2001). The past decade has also witnessed a significant increase in the prevalence of resistance to antifungal agents (Ruhnke et al 1994). In C. albicans, overexpression of Cdr1p is the most frequently reported mechanism of resistance to azole drugs (Cowen et al 2000).…”

Difference in virulence between fluconazole‐susceptible and fluconazole‐resistant Candida albicans in a mouse model

“…The development of fluconazole-resistant (FLU-R) Candida albicans isolates during treatment of oropharyngeal candidosis (OPC) has been frequently described in AIDS patients. [1][2][3][4] Acquired FLU resistance has thus been identified as an important cause of clinical failure and relapse in FLU-treated AIDS patients with OPC. Several molecular mechanisms for development of resistance have been described: (i) decreased intracellu-lar accumulation due to activation of the efflux pumps caused by (ii) overexpression of the CDR genes as well as the MDR1 gene and (iii) alterations in lanosterol demethylase due to point mutations in the ERG genes.…”

Heterogeneity in antifungal susceptibility of clones of Candida albicans isolated on single and sequential visits from a HIV‐infected southern Chinese cohort

“…Candida albicans is still the major Candida species responsible for oropharyngeal candidiasis (6)(7)(8)(9). However, due to inadequacy of treatment regimens to eradicate oropharyngeal candidal carriage and partly due to genetic shifts, resistant strains of C. albicans and other non-albicans species such as C. glabrata and C. krusei are emerging worldwide (6,10,11).…”

“…For instance, of HIV-infected patients with symptomatic candidiasis, 80-100% recover within 5-10 days of fluconazole therapy (2,4,6,10) although 20-100% of such patients relapse within a month once treatment is stopped (2,3,6,10). In the latter group, the fluconazole resistance of C. albicans strains isolated increases dramatically [e.g., minimum inhibitory concentration (MIC) increases from 6.3 mg/ml to 100 mg/ml] (7,8,11,20,28). There is no satisfactory explanation for this phenomenon, and the monitoring of comparative susceptibility data for isolates recovered before and during treatment may help identify the origin of such fluconazole resistance.…”