Correlation between in vitro susceptibility ofCandida albicans and fluconazole-resistant oropharyngeal candidiasis in HIV-infected patients

Abstract

Twenty-five patients seen consecutively at an HIV outpatient clinic who had clinical evidence of oropharyngeal candidiasis and two or more oral swabs positive for yeasts on culture were studied retrospectively. For each of the 65 isolates susceptibility to fluconazole was evaluated by the disk diffusion test and determination of the minimal inhibitory concentration (MIC). A correlation was sought between clinical resistance and in vitro susceptibility data. Seven patients were non-responders and 19 were responders (one patient figuring in both groups). Significant differences were observed between the two groups with respect to the median interval after the diagnosis of AIDS (27 months in non-responders and 2 months in responders; p = 0.001), the median CD4+ cell count (6 and 21 cells/mm3 respectively; p = 0.005) and the median number of previous episodes of oropharyngeal candidiasis treated with fluconazole (13 and 2 episodes respectively; p = 0.001). Candida albicans was identified in 64 of 65 cultures. The correlation between MIC values and diameters of inhibition was good (r = 0.85; p < 0.001). The degree of in vitro susceptibility of the isolates to fluconazole showed a significant difference between non-responders and responders (mean inhibition diameters 13 and 36 mm respectively; p < 0.001) with a tentative cut-off value of 25 mm. An advanced stage of HIV infection and previous exposure to fluconazole could be risk factors for the development of fluconazole-resistant oropharyngeal candidiasis. Candida albicans strains with decreased in vitro susceptibility to fluconazole were responsible for the clinical resistance which could be predicted by a simple disk diffusion test.

Population pharmacokinetics of fluconazole given for secondary prevention of oropharyngeal candidiasis in HIV-positive patients

“…The susceptibility of Candida Albicans towards¯uconazole was determined at each visit with a disk di usion agar test using 50 lḡ uconazole [7]. The inhibition diameter (mm) was measured, and microbiological resistance was de®ned as an inhibition diameter on an agar plate smaller than 25 mm.…”

“…This strategy presents advantages with respect to cost, compliance and drug interactions [6]. However, increased resistance tō uconazole has been reported during prophylactic therapy [7].…”

Evaluación de la susceptibilidad de especies de Candida al fluconazol por el método de difusión de disco.

“…Pero tal vez más notorias fueron las fallas observadas a partir de 1985 en pacientes con sida y mucositis candidiásica bajo tratamiento con fluconazol, quienes desarrollaban candidiasis orofaríngea crónica refractaria a la terapia (9)(10)(11). Esta resistencia fue comprobada por las altas concentraciones inhibitorias mínimas (CIM) de los correspondientes aislamientos (12)(13)(14)(15) …”

Fluconazole and Voriconazole Multidisk Testing of Candida Species for Disk Test Calibration and MIC Estimation

“…This emergence of resistance to drugs has led to a growing demand for susceptibility testing of clinical yeast isolates (14,32,41,43). Comparisons between the standardized NCCLS broth macrodilution method (27) and microdilution methods (12,22,33,38), Etests (7,8,12,25,33,38), and disk diffusion methods (2,3,26,35,36,41) suggest a possibility of using the less expensive disk method in clinical microbiology laboratories. We have extended the analysis of azole disk diffusion tests by using singlestrain regression analysis (SRA) for studying azole regression lines among Candida species and for calibration of the disk test.…”

“…Particularly in AIDS patients with oropharyngeal and/or esophageal candidiasis there have been reports of increased azole resistance among Candida isolates (6,14,24,29,(32)(33)(34)44). This emergence of resistance to drugs has led to a growing demand for susceptibility testing of clinical yeast isolates (14,32,41,43). Comparisons between the standardized NCCLS broth macrodilution method (27) and microdilution methods (12,22,33,38), Etests (7,8,12,25,33,38), and disk diffusion methods (2,3,26,35,36,41) suggest a possibility of using the less expensive disk method in clinical microbiology laboratories.…”