Study On The Resistance Mechanism Of Invasive Candida Albicans To The Drug Resistance Of Azole

Background:In recent years,with the rapid development of medical technology,various kinds of intubation,immunosuppressive agents,radiotherapy and chemotherapy have been used to increase the incidence of candidiasis in hospitals.The patients and their families are burdened with great pain and high financial burden because of the many basic diseases,poor therapeutic effect and high fatality rate.As the frequency of preventive and therapeutic use of antifungal drugs has increased significantly in the past,drug resistance of candida isolates has also appeared.In order to better prevention and control nosocomial infection beads the incidence of bacteremia,formulate scientific and reasonable prevention and control measures,at the same time explore candida of azole antifungal drug resistance mechanism,better reasonable use of antifungal drugs,this study collected the first affiliated hospital of nanchang university in February 2015 to August 2016 beads bacteremia in patients with blood separation of pathogenic fungi,identified in vitro susceptibility test for azole antifungal drug resistance of c.albicans and tropical candida,by PCR amplification ERG11 gene and ERG3 and two-way sequencing,to compare the results with the gene pool standard strain analysis,find the mutation,explore candida of azole antifungal drug resistance mechanisms,for clinical early prevention,early diagnosis,early treatment and improve prognosis provide evidence-based basis.Purpose:1,The collection of pathogenic fungi,candida hematic disease patients to carry on the strain identification and drug sensitivity test in vitro,select azole antifungal drug resistance of c.albicans,tropical candida strains;2.To explore the resistance mechanism of candida albicans and candida albicans to azole antifungal drugs.Methods:To collect the first affiliated hospital of nanchang university hospital patients,separation of fungi in the blood,the morphology,molecular biology identification,identified as c.albicans and tropical candida,then apply the American institute of standardization of clinical trials M27-in vitro medicine sensitive experiment scheme A3,and screened azole antifungal drug resistance of resistant strains.Gene ERG11 and ERG3 were amplified by PCR amplification,and the mutation sites were identified by comparison analysis in NCBI gene,and the correlation between the mutation and drug resistance was analyzed.Results:1,Isolated from candida hematic disease patient’s blood the CPC 52 strains of candida,17 tropical candida strains(32.69%),16 strains of c.albicans(30.77%),smooth candida 14 strains(26.92%),other 2 strains of candida.One strain of candida albicans and 6 strains of candida albicans were found.2.6 strains of candida albicans and 6 strains of candida albicans were screened by in vitro drug susceptibility test.3.One strain of candida albicans did not detect missense mutations;Two(T381C,T432C)synonymous mutations were found.ERG11 gene found 2(T394C,C615A)missense mutations,resulting in the 132 nd tyrosine mutation as histidine,the 205 th tyrosine mutation to glutamic acid,and 2(T485A,C795T)synonymous mutations;3,6 strains of candida tropical ERG11 found 2(A395T C461 T,)missense mutation,leading to 132 th tyrosine mutation of phenylalanine,154 th serine mutations of phenylalanine,and three(T225C G264 A,T35G)synonymous mutations;ERG3 genes found seven(T35G,334 g,A527 G,T35A,C815 A,C820A,T38A)missense mutation: lead to 12 th leucine mutations of histidine,112 th glycine,serine mutations 176 th as aspartic acid,alanine mutations 272 th proline mutated into glutamine,274 th histidine mutations of asparagine,13 th mutated into tyrosine,phenylalanine 205 th tyrosine mutations of histidine,and 4(A366G T912 A,C528A,T531C)synonymous mutations.Conclusion:1.The proportion of candida albicans in our hospital was the highest,followed by candida albicans,and candida albicans was the first in our hospital.2.Candida albicans,candida albicans and candida albicans,have a certain proportion of resistance to azole antifungal drugs.3.The resistance mechanism of candida albicans and candida albicans was related to the mutations of ERG11 and ERG3 genes.