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

Abstract

The increased frequency and severity of candidal infections in human immunodeficiency virus (HIV)-infected individuals has prompted the wide use of antifungals, such as amphotericin B, ketoconazole, and fluconazole, resulting in the emergence of drug-resistant strains of Candida albicans. To study this phenomenon in an ethnic Chinese cohort, we isolated multiple colonies of Candida from the oral cavities of 16 HIV-infected patients on single and subsequent sequential visits over a period of 12 months. Ten of the 16 patients had sporadic episodes of oropharyngeal candidiasis (Group A), while the remainder were asymptomatic with respect to this condition (Group B). Oral rinses were collected and immediately processed in the laboratory for the isolation of C. albicans in a standard manner. A total of 433 C. albicans isolates were tested for their susceptibility to amphotericin B, ketoconazole and fluconazole by an agar diffusion method using the commercially available E-test. All tested isolates demonstrated variable susceptibility to amphotericin B, ketoconazole and fluconazole. The minimum inhibitory concentration (MIC) of the isolates for amphotericin B, ketoconazole and fluconazole ranged from <0.002-1.5 microg/ml, <0.002-4.0 microg/ml and <0.016-32 microg/ml, respectively. Sequential isolates of a few patients demonstrated variable susceptibility to all the antifungals, and no discernible MIC pattern emerged either in group A or B over time. Interestingly, significant variation in antifungal susceptibility was also noted in isolates obtained from the same patient on a single visit. Sequential yeast isolates in 9 of 16 patients (56%) demonstrated significant differences in MIC within and between visits for both amphotericin B and ketoconazole, while a lower percentage--44%(7/16)--exhibited this trait for fluconazole. Our study demonstrates the diversity in antifungal susceptibility in either commensal or "infective" oral strains of C. albicans in HIV disease, and shows the need for vigilance for the emergence of resistant strains, and for frequent antifungal susceptibility studies.

A prospective analysis of the genotypic diversity and dynamics of the Candida albicans colonizing flora in neutropenic patients with de novo acute leukemia

“…Altogether, there was no evidence in favor of the selection of resistant clones or the replacement of the original strain upon antifungal drug pressure in our study, suggesting that these events are rare in neutropenic leukemia patients receiving topical amphotericin B along with clear indications for systemic antifungals over a period of up to 6 months. This is in contrast with studies conducted in patients with human immunodeficiency virus infection, 20,40 which found that different subpopulations of colonizing or infecting strains could co-exist at a given time in the same patient and exhibit different patterns of susceptibility to antifungal drugs. We believe that such a discrepancy could reflect the different populations of patients studied (i.e.…”

`Genotypic shuffling’ of sequential clones of Candida albicans in HIV-infected individuals with and without symptomatic oral candidiasis

“…This, in turn, implies that subclones of C. albicans with variable genotypes may colonize the oral cavity simultaneously. In this event, it is difficult to determine with certainty the contribution, if any, of individual clones to infection (Soll et al ., 1988; Johnson et al ., 1995) and, further, the presence of more than one clonal type may have important therapeutic implications, as some may have different susceptibilities to antifungal agents (Korting et al ., 1988; Pfaller et al ., 1994; Samaranayake et al ., 2001). However, little is known of clonal variations in C. albicans during either recurrent episodes of oral candidiasis or asymptomatic carriage over prolonged periods in HIV disease.…”

Oral candidal carriage correlates with CD4+ cell count but not with HIV and highly active antiretroviral therapy status

“…Microbiological samples were obtained using the concentrated oral rinse method previously described by Samaranayake et al Samples were inoculated on Sabouraud's chloramphenicol agar and incubated aerobically at 37°C for 48 hours. Presumptive identification of the Candida colonies isolated was carried out through Gram stain, germ tube test and culture on CHROMagar (Himedia).…”

“…Microbiological samples were obtained using the concentrated oral rinse method previously described by Samaranayake et al 7…”