الفهرس 
Candida speciesOnly 14 pages are availabe for public view
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Abstract
This work was done in attempt to investigate the distribution of the Candida species among immunocompromised patients, to determine their susceptibilities to azole antifungal agents including fluconazole, itraconazole and voriconazole, to assess the size of problem of azole resistant Candida in MUH especially among immunocompromised patients and to detect causes that contribute to azole resistance in Candida species. In this present study, 468 immunocompromised patients were categorized into 4 groups and subjected to; Proper samples were taken from each case of the 4 studied groups; Mycological examination; Antifungal susceptibility testing were done for isolated Candida spp. to detect azole resistant Candida by M-27 A2 (microbroth dilution) and M-44 A (disk diffusion) according to CLSI; Amplification of ERG 11 gene in azole resistant Candida was done by PCR followed by sequencing to detect point mutation in ERG 11 which code for 14 α demethylase (target site for azoles). In group I (patients with solid tumors receiving radiotherapy), the highest recovery rate of Candida infection was UTI (11.9%). C. albicans was the most common Candida spp. causing oropharyngeal candidiasis (57.1%) and skin infections (66.75%), while C. tropicalis was the most common Candida spp. causing blood stream infection (40%) and UTI (30%). In group II (patients with leukemias and lymphomas), the most common recovery rate of Candida infection was oropharyngeal infection (3.99%). C. albicans was the most common Candida spp. causing skin infections (100%) and LRTI (37.55%), while C. glabrata was the most common Candida spp. causing oropharyngeal infection (33.3%) and C. tropicalis was the most common Candida spp. causing UTI (66.7%) and blood stream infection (50%). In group III (neonates in neonatal ICU), the most common recovery rate of Candida infection was BSI (17.4%). C. albicans was the most common Candida spp. causing skin infections (100%) and, blood stream infection (53.3%) while C. parapsilosis was the most common Candida spp. causing UTI (60%). In group IV (children in children’s ICU), the most common recovery rate of Candida infection was UTI (15.3%). C. albicans was the most common Candida spp. causing UTI (36.4%) and LRTI each (60%) and both C. albicans and C. parapsilosis were the most common Candida spp. causing BSI (each 33.3%). In all groups, the recovery rate of C. albicans was highest with prophylactic quinolones followed by 3rd generation cephalosporines. The recovery rate of NAC was higher in patients receiving empirical fluconazole than other patients. Azole resistance rate according to CLSI broth microdilution was highest with fluconazole (28%) and least with voriconazole (9%). While, azole resistance rate by disk diffusion method was highest with fluconazole (24%) and least with voriconazole (3%). C. kreusi was the most resistant species to azoles followed by C. glabrata then C. albicans. While, C. tropicalis, C. parapsilosis and C. dubliensis were the most sensitive species. Fluconazole resistance was higher among patients receiving empirical fluconazole (53.7%) than others. Nine Candida isolates (2 C. albicans, 3 C. glabrata and 4 C. kreusi isolates) showed cross resistance against fluconazole, itraconazole and voriconazole. Two point mutations (subsitution) causing nucleotide substitutions with misense mutation were present in 2 strains (C. albicans and C. glabrata). While, the other 7 cross resistant strains subjected to the study were found to have no point mutation in ERG 11. Empirical fluconazole in C. albicans isolates with ERG11 point mutation and in C. albicans isolates without ERG11 point mutation carry OR =1 (equal risk). While in C. glabrata and C. kreusi empirical fluconazole carry OR less than 1. Conclusions: We have shown that NAC was higher than C. albicans especially with empirical fluconazole, although at individual species level, the C. albicans is the predominant species in MUH. Fluconazole, remain effective agent as empirical therapy against most major Candida isolates in MUH except C. glabrata and C. kreusi. Empirical quinolones and 3rd generation cephalosporines were associated with increased risk of invasive candidiasis. Voriconazole was more effective than fluconazole with low resistant rates among fluconazole resistant Candida. Disk diffusion showed good agreement with microbrothdilution method for antifungal susceptibility testing as regarding sensitivity and specificity. Among azole cross resistant Candida isolates ERG 11 mutations were detected.