| Candida spp was the important opportunistic pathogen in the clinic, including Candida albicans, Candida tropicalis, Candida glabrata, and Candida krusei four of which is above of 90% for overall yeast isolates. Systemic Candida infections is a related to advances in medical treatment and increasing numbers of immunocompromised patients, particularly the AIDS, comprehensive application of antibiotics and steroids, invasive manipulation, hypoimmnuity, cancer chemotherapy, and organ and bone marrow transplantation. Fluconazole is the most frequently employed agent. However, longterm fluconazole treatment often lead to the rapid development of resistance and cross-resistance in azole drugs.Many different types of mechanisms are known to contribute to a azole-resistant phenotype in Candida. The most frequent resistance mechanisms include i .upregulation of ERG 11,which encodes the azole drug target enzyme C14ot-demethylase and is importance enzyme of the ergosterol biosynthetic pathway. ii .the decreased affinity of azoles to cellular targets, often due to amino acid substitutions in the cytochrome P-450 C14x-demethylase. A defective C14x -demethylase will result in the accumulation of 14x-methyl sterols, especially 14a -methyl fecosterol. In azole-treated cells, the presence of 14x-methyl sterols can modify the function and fluidity of the plasma membrane., iii.increased efflux of the drug from the cell by overexpressing efflux pumps. Two types of efflux pumps are known to related with azole-resistance and are ATP binding cassette transporter superfamily(cdr1 cdr2) and major facilitators superfamily(mdrl).Recently, Problems with an increase in the incidence of systemic fungal infections make to emphasiz the prevention and surveillance of nosocomial systemic fungal infection, study the epidemiology and resistance mechanisms of yeast. In order to obtain the data of the epidemiology of Candida in Tianjin for controlling infections and know the fungal resistance of Candida for the guidance of rational use of antifungal-drug, this study collected clinical isolates of systemic Candida infection from five Tianjin hospitals in 2002 and anylazed them. To study the rapid accurate gene identification method of commom pathogenic Candida species and lay the foundation of molecular diagnosis for clinical systemic candidiasis and investigate the susceptible sites of nosocomial systemic Candida albicans infection in Tianjin area, explore the genotype and corresponding susceptibility analysis. We also preliminary study the Molecular mechanisms of resistance to fluconazole in Candida tropicalis clinical strains.Part 1: The study on the surveillance of clinical isolates of Candida species in TianjinObjective: To investigate the epidemiology and the antifungal drug resistance of systemic Candida infectious clinical isolates from five Tianjin hospitals in 2002 for the guidance of rational use of antifungal and control of hospital infection. Methods: All collected Candida clinical isolates were analyzed by WHONET5 software. Antimicrobial susceptibility was tested by microdilution broth procedure. The standards followed NCCLS.Results: We collected 53 Candida clinical isolates. Candida albicans were 47.17%,which was most, secondly was Candida tropicalis of 26.42%.The major systemic Candida infection site was lung which was 69.81%, and geriatric group (54.72%) was more vulnerable and all with other primary disease. Comprehensive application of antibiotics and steroids, invasive manipulation and hypoimmnuity were risky factors. Candida were all susceptibility for ketoconazole and 5-flucytosin. Candida albicans and Candida tropicalis were more susceptibility for fluconazole than Candida krusei and Candida glabrata, susceptibility rate was 100%,92.9%,40%,62.5% respectively. Four Candida genus were some resistant to amphotericin B, susceptibility rate was Candida albicans 84%> Candida tropicalis 64. 3% Candida glabrata 75% Candida krusei 60%, respectively. Conclusion: Candida spp is a major opportunistic pathogen that...
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