Replacement of Candida albicans with C. dubliniensis in Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis Treated with Fluconazole

Abstract

Candida dubliniensis is an opportunistic yeast that has been increasingly implicated in oropharyngeal candidiasis (OPC) in human immunodeficiency virus (HIV)-infected patients but may be underreported due to its similarity with Candida albicans. Although most C. dubliniensis isolates are susceptible to fluconazole, the inducibility of azole resistance in vitro has been reported. Thus, the use of fluconazole prophylaxis in the treatment of these patients may have contributed to the increasing rates of isolation of C. dubliniensis. In this study, yeast strains were collected from the oral cavities of HIV-infected patients enrolled in a longitudinal study of OPC. Patients received fluconazole for the suppression or treatment of OPC, and isolates collected at both study entry and end of study were chosen for analysis. Samples were plated on CHROMagar Candida medium for initial isolation and further identified by Southern blot analysis with the species-specific probes Ca3 (for C. albicans) and Cd25 (for C. dubliniensis). Fluconazole MICs were determined by using NCCLS methods. At study entry, susceptible C. albicans isolates were recovered from oral samples in 42 patients who were followed longitudinally (1 to 36 months). C. albicans strains from 12 of these patients developed fluconazole resistance (fluconazole MIC, >64 g/ml). C. dubliniensis was not detected at end of study in any of these patients. Of the remaining 30 patients, eight (27%) demonstrated a replacement of C. albicans by C. dubliniensis when a comparison of isolates obtained at baseline and those from the last culture was done. For the 22 of these 30 patients in whom no switch in species was detected, the fluconazole MICs for initial and end-of-study C. albicans isolates ranged from 0.125 to 2.0 g/ml. For the eight patients in whom a switch to C. dubliniensis was detected, the fluconazole MICs for C. dubliniensis isolates at end of study ranged from 0.25 to 64 g/ml: the fluconazole MICs for isolates from six patients were 0.25 to 2.0 g/ml and those for the other two were 32 and 64 g/ml, respectively. In conclusion, a considerable number of patients initially infected with C. albicans strains that failed to develop fluconazole resistance demonstrated a switch to C. dubliniensis. C. dubliniensis in this setting may be underestimated due to lack of identification and may occur due to the impact of fluconazole on the ecology of oral yeast species.

Fluconazole impacts the extracellular matrix of fluconazole-susceptible and -resistant Candida albicans and Candida glabrata biofilms

“…Resistance to antifungal agents can be defined as the persistence or progression of infection after application of antimicrobial treatment [16,17]. Some studies have observed the emergence of resistant microorganisms during long-term or prophylactic treatment [18,19]. Intrinsic or primary resistance occurs when a microorganism has low susceptibility to a medication, before its exposure to the agent.…”

Distribution of Candida dubliniensis from Denture Membrane Surfaces

“…dubliniensis (19). It did not occur in the replacement of both species in this study because the subjects were healthy individuals.…”

In vitro activities of antifungal agents alone and in combination against fluconazole-susceptible and -resistant strains of Candida dubliniensis

“…TRB+VRZ resulted on 53.33% of indifference and synergy decreased The increased use of antifungal agents may have contributed to the development of highly resistant microorganisms or those which are more prone to develop resistance to drugs such fluconazole. 11 Although most C. dubliniensis clinical isolates are susceptible to azole derivatives, resistant strains have been recovered from oral cavities of human immunodeficiency virus (HIV)-infected patients with oropharyngeal candidiasis and prior exposure to fluconazole. 8,12 Thus, combining antifungal agents has been suggested as an alternative strategy, and the use of terbinafine in combination with azoles has been suggested as a potential therapeutic option.…”