| Objective:Through the analysis of Jilin province mycobacterium tuberculosis(MTB)in drug resistance present situation and the related gene mutation characteristics,especially for Jilin province tuberculosis of multi-drug resistant tuberculosis(MDR-TB)ratio of clinical medicine and preventive control strategy to provide important technical support,to control the growth rate of drug-resistant TB,for optimizing the clinical use of drugs,in order to improve the treatment success rate,reduce the recurrence,and promote resistance management of patients with TB prevention and control is of great significance.Methods:1091 cases of MTB from January 2016 to September 2018 were collected and sent to the TB reference laboratory in Jilin province,along with relevant information on the source of the cases.The drug susceptibility test was conducted by proportion method,including isoniazid(INH),rifampicin(RFP),streptomycin(SM),ethambutol(EMB),kanamycin(KM),amikacin(AMK),capreomycin(CPM)and OFX(OFX),a total of 8 drugs.A total of83 strains(43 resistant strains and 40 sensitive ones)were studied for second-line drug resistance genes,and a total of 9 related drug resistance genes(rrs,eis,tlyA,gyrA,Rv0148,Rv2005c,Rv2744c,ppnk,bfrB)were studied.Measurement data are expressed as)43(ąS.The rate or composition ratio of counting data was expressed,and the rate of drug resistance among different characteristics was compared by chi-square test,the factors affecting drug resistance were analyzed by Logistic regression,the sequence splicing of gene fragments was conducted by DNAstar software,and the comparison of genes was conducted by MEGA5 software.P<0.05 was considered statistically significant.Results:1.Overall resistance:in 1091 MTB,at least one anti-tuberculosis drug was resistant to 423 strains,and the drug resistance rate was 38.77%.The resistance rate of primary treatment was 35.67%,and the rate of retreatment was 53.09%.2.Drug resistance of various types:the single drug resistance rates of first-line anti-tb drugs INH,RFP,EMB and SM were 3.85%,3.48%,1.28%and 9.07%,respectively.The single-drug resistance rates of second-line anti-tb drugs KM,AMK,OFX and CPM were 1.01%,0.37%,7.06%and 0.73%,respectively.MDR-TB was10.54%,poly-drug resistance was 8.89%,and XDR-TB was 1.74%.The drug resistance rates of INH,RFP,EBM,SM,AMK,KM,OFX and CPM in any form were 19.62%,17.05%,9.81%,24.75%,3.76%,4.95%,9.53%and 3.39%,respectively.MDR accounted for 61.8%in RR-TB.Drug resistance sequence:the top five were:SM(24.75%),INH(19.62%),RFP(17.05%),EBM(9.81%),OFX(9.53%)?3.Analysis of influencing factors:(1)there was a significant difference in the type of drug resistance between the two groups(?~2=20.385,P<0.001).(2)the types of cases and residence were the influencing factors of MDR.Retreatment patients are 3.373 times more likely to develop MDR(OR=3.373,95%CI:2.123~5.119)than newly treated patients.People living in cities are 1.846 times more likely to develop MDR than rural patients(OR=1.846,95%CI:1.241~2.744).(3)The age difference of MDR TB was statistically significant(?~2=15.847,P<0.05).(4)the types of cases and residence were the influencing factors of RR-TB.Retreatment patients are 3.101times more likely to develop RR-TB(OR=3.101,95%CI:2.172~4.427)than newly treated patients.People living in cities are 1.409 times more likely to develop RR-TB than rural patients(OR=1.409,95%CI:1.013~1.959).4.Gene mutation:(1)all rrs genes were mutated at A1401G,and the mutation rates of AMK,KM and CPM resistant strains were 100%,93.33%and 87.5%,respectively.The eis gene was mutated at two sites in one sensitive strain.Rv2005c gene mutation occurred in 51 strains of MTB,and the mutation site of 50 strains was from position 279 C to T,but there was no difference between drug resistance and sensitivity.Rv2744c gene mutation occurred in 7 strains of MTB.A total of 68strains of bfrB gene were mutated,and 67 of them were detected to mutate from A to G at 468,but there was no difference between drug resistance and sensitivity.The Rv0148 gene had multilocus mutation in 3 strains.(2)No tlyA gene or ppnk gene mutations were detected in the 16 CPM resistant strains,and there were individual mutations in the sensitive strains.(3)mutation was detected in 25 strains of gyrA gene,with mutation rate of 78.13%,mutation codon range of 90-100,mutation frequency of the most was 90th and 94th,no mutation was found in the sensitive strain.Conclusion:1.The total drug resistance rate of 1091 strains of MTB was 38.77%,RR-TB17.05%,MDR-TB was 10.54%,poly-drug resistance rate was 8.89%,and XDR-TB was 1.74%.2.The drug resistance rate of the four first-line drugs was 37.30%,and the drug resistance rate of the four second-line drugs was 13.93%.3.The sequence resistance top five order from high to low was:SM(24.75%),INH(19.62%),RFP(17.05%),EBM(9.81%),OFX(9.53%).4.Drug resistance rates are different in pathological types,multi-drug resistance is different in age,case type and residence are the influencing factors of MDR-TB and RR-TB.5.AMK,KM and CPM show high cross-resistance.The mutation rates of rrs gene in AMK,KM and CPM resistant strains were 100%,93.33%and 87.5%,respectively,and A1401G mutation occurred in all strains.6.No mutation was found in eis,Rv2005c,Rv2744c,bfrB,Rv0148,tlyA and ppnk genes that could be used as drug resistance markers.7.The mutation rate of the OFX drug-resistant gyrA gene was 78.13%,and the mutation sites were mainly concentrated at the 90th,91st and 94th positions of the codon. |
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