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Analysis Of The Drug Resistance Mechanism,epidemiology And Combined Drug Regimen Of Carbapenem-resistant Acinetobacter Baumannii

Posted on:2021-01-31Degree:MasterType:Thesis
Country:ChinaCandidate:Z W WuFull Text:PDF
GTID:2404330614964421Subject:Clinical Laboratory Science
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Objective :(1)Understanding the resistance of carbapenem-resistant Acinetobacter baumannii(CRAB)which is isolated from our hospital from 2015 to 2019,summarizing the detection rate of CRAB,and analyzing the departmental distribution and specimens of CRAB Source situation.(2)We collecting 42 strains of CRAB in intensive care unit(ICU)from January to June 2019 to study the mechanism of drug resistance and analyze its molecular epidemiological characteristics.(3)Exploring a combined drug regimen for CRAB to provide a reliable basis for clinical anti-infection treatment and to improve patient prognosis.Method:(1)Using Whonet5.6 to retrospectively analyze CRAB drug resistance in our hospital from 2015 to 2019,and comparing the drug sensitivity results of Acinetobacter baumannii(AB)and CRAB isolates in the past five years,summarizing the detection rate of CRAB and analyzing the CRAB Specimen source and department distribution,Analyzing and organize data through SPSS20.0(2)Detection of carbapenemase genes(OXA-23,OXA-24,OXA-48,OXA-51,OXA-58,KPC,VIM,IMP,NDM)in CRAB by polymerase chain reaction(PCR).(3)The expression of CRAB efflux pump was analyzed by efflux pump suppression experiment.(4)The multi-site sequence typing(MLST)technique was used to analyze the clone correlation and molecular epidemiological characteristics of CRAB.(5)The drug susceptibility test of the four combined drug regimens was carried out by using the micro checkerboard dilution method to analyze the antibacterial activity of different antibacterial drug combinations against CRAB.The combined programs are:imipenem + polymyxin E,imipenem + tigecycline,minocycline + polymyxin E,ciprofloxacin + tigecycline.Results:(1)Drug resistance analysis shows that CRAB’s resistance to commonly used antibacterials was higher each year from 2015 to 2019.The comparison of drug susceptibility results of AB and CRAB isolates in the past five years shows that AB has the lowest resistance rate to levofloxacin and compound sinomine,which are40.52% and 58.06%,respectively.The resistance rates to other antibacterial drugs are all > 72.48%.In addition to CRAB,except for slightly lower resistance rates to levofloxacin(50.95%)and compound neonomine(72.62%),the resistance rates to 12 other conventional antibiotics were all> 93.04%.The antibacterial activity of levofloxacin against CRAB in quinolone antibiotics was higher than that of ciprofloxacin.The resistance rates of the two were 50.95% and 99.45%,respectively,and the difference was statistically significant(P <0.05).The resistance rate of CRAB to 14 antibacterial drugs in this study was higher than AB,except for ceftizolin,cefuroxime,cefotetan,and furantoin,the differences were statistically significant(P<0.05).(2)The detection rate of CRAB from 2015 to 2019 was 76.95%,and the annual detection rate showing a decreasing trending year by year,and the difference was statistically significant(P < 0.05).(3)Departments were the largest in ICU(30.26%),neurosurgery(17.82%),and respiratory medicine(15.01%),the source of specimens was mainly sputum(81.15%).(4)The 42 CRAB strains in this study all carried the genes OXA-23 and OXA-51,of which OXA-51 was an inherent gene of Acinetobacter baumannii.No OXA-24,OXA-48,OXA-58,KPC,VIM,IMP and NDM genes.(5)The efflux pump phenotypic test results shows that the minimum bacteriostatic concentration(MIC)of imipenem decreased by 4-8 times for 16 strains after the addition of carbonyl cyanochlorophenylhydrazone(CCCP).The positive rate of phenotypic pump phenotype of the experimental strains was 38.1%(16/42).(6)42strains of CRAB were divided into 10 ST types,mainly ST1145(13 strains),ST1417(8 strains)and ST208(7 strains),and the remaining types were ST1658 4 strains,ST540 3 strains,2 strains each of ST 938 and ST 195,1 strain each of ST 1779,ST1696 and ST 1646.Only two alleles(gpi and rec A)are different between ST1417 and ST208.Only one allele gpi differs between ST1145 and ST1417.The allele profiles of ST1145 and ST208 are also rec A The difference is that the remaining six alleles are consistent,indicating that there is a certain degree of parentage among the resistant strains.(7)The combined drug sensitivity results shows that the MIC value of the combined drug group of most strains was lower than that of the single drug treatment.The four combination schemes can be considered in clinical practice to achieve better bactericidal effects,especially only the performance Synergistic and additive effects of imipenem + polymyxin E group and minocycline + polymyxin E group.Conclusions:(1)The resistance of CRAB isolates in our hospital to commonly used antibacterial drugs is severe.In the past five years,the detection rate of CRAB has decreased.The distribution of CRAB departments was the highest in ICU(30.26%).The source of the specimens was mainly sputum(81.15%).(2)CRAB’s resistance mechanism is mainly carbapenemase producing the OXA-23 genotype,followed by efflux pump expression.(3)The 42 CRAB strains are mainly ST1145(30.95%),ST1417(19.05%),and ST208(16.67%),and only one or two alleles differ between different ST types gene,genetically related clone.(4)The combination of imipenem +polymyxin E and minocycline + polymyxin E have better antibacterial effect on CRAB and can be used as a clinical anti-infective treatment New idea.
Keywords/Search Tags:Carbapenem-resistant Acinetobacter baumannii, Resistance mechanism, Epidemiology, Combined drug sensitivity test
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