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Objective:To explore the precision treatment effect of multidrug-resistant pulmonary tuberculosis (MDR-PTB) based on the proportion method for drug susceptibility test, and to provide a scientific basis for formulating MDR-PTB treatment plan.Methods:One hundred and eighty patients with MDR-PTB treated in Shenzhen Center for Chronic Disease Control from January 5, 2016 to April 30, 2018 were enrolled. The initial treatment plan after diagnosis was six months of amikacin (AM), pyrazinamide (Z), levofloxacin (LFX), ethambutol (E), prothionamide (PTO) and 18 months of Z, LFX, E, PTO. According to whether proportion method for drug susceptibility test for 10 commonly used drugs was implemented, patients were divided into precision treatment group and empirical treatment group. In the precision treatment group, the treatment plans were adjusted according to the results of the drug susceptibility test. The treatment plans and disease outcomes of the two groups of patients were retrospectively analyzed. Chi-square test was used for statistical analysis.Results:Among the 180 patients, there were 113 patients in the precision treatment group and 67 patients in the empirical treatment group. The drug resistance rates of the precision treatment group from low to high were: capromycin (CM) (0, 0/113), AM (2.65%, 3/113) and kanamycin (KM) (2.65%, 3/113), para-aminosalicylic acid (PAS) (7.96%, 9/113), PTO (11.50%, 13/113), ofloxacin (OFX)(38.05%, 43/113), E (39.82%, 45/113), and streptomycin(S) (76.99%, 87/113). In the precision treatment group, the drugs were adjusted for 104 person-times according to the proportion method for drug susceptibility test during the treatment, from low to high: AM (3 person-times), PTO (13 person-times), LFX (43 person-times) and E (45 person-times). The treatment success rate of the precision treatment group was 78.8%(89/113), which was higher than that of the experience treatment group (52.2%(35/67)), the difference was statistically significant ( χ2=13.805, P=0.000 2). In the precision treatment group and empirical treatment group, there were no statistically significant differences of alanine aminotransferase elevated (32.3%(31/96) vs 34.0%(18/53)), serum creatinine elevated (4.2%(4/96) vs 5.7%(3/53)), and white blood cell count decreased (24.0%(23/96) vs 22.6%(12/53)) (all P>0.05). Conclusion:The traditional treatment plan based on the proportion method for drug susceptibility test has a high success rate in the treatment of MDR-PTB, which is still a worthy choice.
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Objective:To evaluate the clinical-application values of whole genome sequencing (WGS) technology to detect the drug resistance feature of second-line injectable drugs (SLIDs) for multidrug-resistant tuberculosis treatment.Methods:The proportional-method drug sensitivity test and the whole gene sequencing technology were used to simultaneously examine the resistance of three SLIDs: kanamycin (Km) and Amikacin(Am) and capreomycin (Cm) in 172 multidrug-resistant tuberculosis (MDR) strains preserved in the strain bank of the Tuberculosis Laboratory of Shenzhen Chronic Disease Prevention and Control Center from 2013 to 2017. The proportional-susceptibility tests were considered as the gold standard to evaluate the sensitivity, specificity and consistency of WGS results. The samples with differences between the two methods were compared with the minimum inhibitory concentration detection method. The McNemar test was used to statistically analyze the detection rates of the two methods, and a P value<0.05 indicated the significant difference between two groups. Results:A total of 172 MDR strains were included in this study. Two mutated genes were identified by the WGS examination: rrs and eis. Among these genes, rrs-A1401G mutation occurred in 58.3% in Am resistant strains, 14/18 in Km resistant strains or 14/14 in Cm resistant strains, respectively. The sensitivity, specificity and consistency of WGS predicted Am were 14/15, 93.6%, and 68.0%, 15/15, 98.1%, and 90.0% in Km, or 14/15, 100%, and 96.0% in Cm. There were 13 strains with inconsistent results by the two methods. One strain was retested by MIC as a drug-resistant strain and other 12 strains were sensitive. There were 11 strains with inconsistent Am test results, and WGS test results showed that 8 strains had rrs-514-A/C mutations, while DST and MIC tests were sensitive. Conclusion:WGS is enough is sensitive and specific for diagnosing SLIDs resistance.