| Objective:This study aimed to better understand the drug resistance characteristics of Mycobacterium tuberculosis in Jiangxi from 2018 to 2021,focusing on the recent transmission,drug resistance characteristics and epidemiological characteristics of multidrug-resistant tuberculosis strains.Methods:1.A total of 414 the isolated strains of clinical specimens diagnosed with pulmonary tuberculosis and sputum smear-positive patients in Jiangxi Provincial Chest Hospital from January 2018 to December 2021 were collected,and baseline data,epidemiological data,medical history data and other information of all study subjects were recorded.The PCR-reverse dot blot method was used for culture identification.The BACTEC MGIT 960 instrumental method was used to perform phenotypic drug susceptibility detection（DST）for anti-tuberculosis drugs,to analyze the characteristics of drug resistance and drug resistance trend of Mycobacterium tuberculosis.The drug resistance characteristics of multidrug-resistant Mycobacterium tuberculosis were described,univariate analysis was used to screen for risk factors for multidrug-resistant tuberculosis（MDR-TB）,and then multivariate logistic regression was used to determine the independent risk factors for MDR-TB.2.From the data in the first part,103 MDR-TB strains were selected.We extracted DNA by CTAB method and whole genome sequencing was performed based on Illumina’s Hi Seq2000 sequencing platform.Based on the data from whole genome sequencing,we can identify genetic diversity in samples.Based on genomic SNP differences,we can construct a phylogenetic tree and further analyze the risk factors influencing MDR-TB transmission.Results:1.（1）Among the 414 cases of tuberculosis,the number of men（72.71%,301/414）was significantly higher than that of women（27.29%,113/414）,and the proportion of patients over 60 years old was the highest among patients of all ages（28.26%,117/414）.（2）The 414 Mycobacterium tuberculosis isolates had the highest rates of arbitrary resistance to INH（37.68%,156/414）and monodrug resistance（2.90%,12/414）.The rates of arbitrary resistance to INH,RIF,EMB and SM in the retreated group were significantly higher than those in the treatment-na?ve group（INH:χ2=69.01,P<0.001;RIF:χ2=88.12,P<0.001;EMB:χ2=41.02,P<0.001;SM:χ2=28.99,P<0.001）.The multidrug resistance rate in the retreated group was significantly higher than that in the treatment-na?ve group（χ2=75.88,P<0.001）.（3）Among the 130 MDR-TB strains,the random drug resistance rate to SM was the highest（71.54%,93/130）,and the random drug resistance rate to Clr was the lowest（1.18%,1/85）.There was a statistically significant difference in the drug resistance rate of amikacin（Am）between MDR-TB patients in the initial treatment group and MDR-TB patients in the retreatment group（χ2=6.62,P=0.01）.There was no significant difference in drug resistance rate（all P>0.05）.（4）The resistance rate of 414 tuberculosis patients to 7 single anti-tuberculosis drugs fluctuated from 2018 to 2021,with no significant increase or decrease,and no significant difference in statistical analysis.The prevalence of broad drug resistance was associated with year variation,with a slight upward trend with year(χ2trend=4.0,P trend=0.045).（5）Univariate analysis of MDR-TB-related influencing factors showed that farmers or unemployed people,people with junior high school education and below,patients with holes in imaging examinations,people with moderate and poor nutritional status,and patients with retreated patients had a higher risk of multidrug resistance.Other factors such as sex,age,BMI,underlying diseases,smoking,alcohol consumption,and delayed diagnosis had little effect on the incidence of MDR-TB（all P>0.05）.The above influencing factors were included in the multivariate logistic regression analysis,the results showed that moderate nutrition or malnutrition were independent risk factors for the occurrence of MDR-TB（AOR=2.48,P=0.001）.The risk of MDR-TB in retreated patients was 4.50-fold higher than that of treatment-na?ve patients（AOR=5.50,P<0.001）.2.（1）Most of the 103 patients with MDR-TB included in the study were men（70.87%,73/103）,more than half of the patients were farmers or unemployed people（59.22%,61/103）,and the population with junior high school education or below accounted for a large proportion（62.14%,64/103）.The phenotypic susceptibility profiles of 103 strains of Mycobacterium tuberculosis showed that the resistance rate of two fluoroquinolones（FQs）was highest among second-line anti-TB drugs（Lfx:53.4%;Mfx:52.4%）.（2）Based on whole genome sequencing technology,it can be known that90.29%（93/103）of MDR-TB strains belong to Lineage2,that is East Asian genotypes,and all belong to Lineage2.2,that is Beijing genotype（100%,93/93）,and9.71%（10/103）of MDR-TB strains belong to Lineage4（European and American genotypes）.（3）Based on the size of the SNP distance between strains,26 of the 103MDR-TB strains formed 11 clusters,and the range of cluster cases ranged from 2 to 5cases.A univariate analysis of factors related to recent transmission of 103 MDR-TB cases showed that farmers or unemployed people were more likely to pose transmission risk than other occupations（OR=2.93,P=0.03）,and retreated patients were closely related to the recent transmission of MDR-TB（OR=3.50,P=0.02）.The results of multivariate analysis showed that retreated patients were an important risk factor for the recent transmission of MDR-TB（AOR=3.17,P=0.04）.（4）There were no significant differences in the resistance rate,pre-extensive drug resistance rate and extensive drug resistance rate of genetic lineage to anti-tuberculosis drugs（P value>0.05）.Conclusion:1.The drug resistance of Mycobacterium tuberculosis in Jiangxi Province is very serious,especially the incidence of MDR-TB.Although the overall trend of drug resistance has remained stable in recent years,the phenomenon of cross-resistance in anti-tuberculosis drugs is widespread and needs attention.2.The resistance rate of fluoroquinolones is high,and their clinical application should be further standardized.3.Retreated patients and malnourished patients are important risk factors for the occurrence of MDR-TB,and they should be focused on and rationally managed and treated in the process of clinical diagnosis and treatment to reduce the risk of MDR-TB.4.Beijing genotype is the main epidemic strain of MDR-TB in this region,and transmission is the main cause of MDR-TB epidemic,it is recommended to pay attention to the prevalence and spread of Beijing genotype.5.Retreated patients are the main driver of the MDR-TB epidemic,and some interventions can be taken,such as early detection of cases,key control of retreated patients,and early screening of close contacts of MDR-TB patients to curb their spread. |
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