Replacement of Candida albicans with C. dubliniensis in human immunodeficiency virus-infected patients with oropharyngeal candidiasis treated with fluconazole.
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 micro 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 micro 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 micro g/ml: the fluconazole MICs for isolates from six patients were 0.25 to 2.0 micro g/ml and those for the other two were 32 and 64 micro 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.
Department of Medicine, Division of Infectious Diseases, The University of Texas Health Science Center at San Antonio, 78245, USA.
Marcos
M
Martinez
José L
JL
López-Ribot
William R
WR
Kirkpatrick
Brent J
BJ
Coco
Stefano P
SP
Bachmann
Thomas F
TF
Patterson
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy* / Q000382:microbiology; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002175:Candida / Q000145:classification* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D002176:Candida albicans / Q000145:classification* / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D002180:Candidiasis, Oral / Q000188:drug therapy* / Q000382:microbiology; D016172:DNA Fingerprinting; D025141:Drug Resistance, Fungal; D015725:Fluconazole / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007621:Karyotyping / Q000379:methods; D008826:Microbial Sensitivity Tests; D016533:Mycological Typing Techniques; D009960:Oropharynx / Q000382:microbiology
D000935:Antifungal Agents; D015725:Fluconazole