Research On Clinical Risk Factors Of Candidemia And Mutation Analysis Of ERG11 Gene In Azole-Resistant Candida Tropicalis

PART1 Analysis of clinical characteristics and risk factors of death with candidemiaObjective To understand the clinical characteristics of candidemia,the risk factors of death,Candida distribution,and antifungal susceptibility,and to promote effective clinical prevention,early diagnosis,and rational drug use.Methods From January 2014 to January 2020,all inpatients over 16 years of age who were positive for the blood culture of Candida in a tertiary hospital were included.Clinical profiles and microbiology materials of the patients were collected from the hospital case system and laboratory system,and used statistical methods to analyze their epidemiological characteristics and risk factors.Results A total of 137 episodes of candidemia were evaluated.The median age of patients was 54.0(43.0,71.0)years,and 57.7% were males.32.1% of all episodes suffered from diabetes.The main predisposing factors were indwelling catheter(63.5%),blood transfusion(60.6%),and admission to ICU(46.7%).27.7% of the patients used antifungal drugs,65.8% of them survived.26.3% of candidemia was caused by Candida albicans,and Candida glabrata was the dominant species(30.7%).Candida tropicalis had the highest resistance rate to antifungal drugs.The separation rate(43.1%)and the fatality rate(56.1%)of ICU wards were both the highest.Diabetes(OR=5.562,P=0.002),hypoalbuminemia(OR=8.464,P=0.000),deep vein catheterization(OR=5.228,P=0.006),and use of hormones/immunosuppressants(OR=3.809,P=0.046)increased the risk of death,and preventive antifungal therapy(OR=0.306,P=0.048)can improve the prognosis of patients.Conclusion The patients with candidemia were older,more complicated,more widely distributed,more invasive procedures,higher mortality rate and higher drug resistance rate.Diabetes,hypoalbuminemia,deep vein catheterization,and the use of hormones/immunosuppressants were independent risk factors for the death of patients with candidemia,moreover,the prophylactic use of antifungals was only a protective factor for survival of patients with candidemia.PART2 Mutation analysis of ERG11 gene in zaole-resistant Candida tropicalisObjective To analyze the mutation of ERG11 gene in clinical isolates of Candida tropicalis and explore its relationship with azole resistance.Methods 52 isolates of Candida tropicalis were randomly selected from the bacteria preservation library of the laboratory of a hospital.After drug sensitivity verification of all strains,the ERG11 gene was amplified by PCR,and the amplified products were sequenced in two directions.The sequencing results were compared with the standard sequences in NCBI Gen Bank,and the mutation sites were analyzed.Results The mutations of the ERG11 gene in azole-resistant and susceptible strains of Candida tropicalis were different.It was found that A395 T and C461T(corresponding to y132 f and s154 f amino acid substitution sites respectively)existed in the ERG11 gene of azole-resistant strains,while only synonymous mutations occurred in the ERG11 gene of susceptible strains.Conclusion Mutation of the ERG11 gene in Candida tropicalis is involved in the occurrence of azole resistance.