Analysis of resistant genetic mutations and characteristics of multidrug-resistant/rifampicin-resistant Mycobacterium tuberculosis in Wenzhou
WU Lianpeng1, 2, XU Ke1, 2, HE Guiqing2, 3.
1.Department of Clinical Laboratory Medicine, the Dingli Clinical Institute of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou 325000, China; 2.Key Laboratory for Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou, Wenzhou 325000, China; 3.Department of Infectious Disease, the Dingli Clinical Institute of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou 325000, China
WU Lianpeng,XU Ke,HE Guiqing. Analysis of resistant genetic mutations and characteristics of multidrug-resistant/rifampicin-resistant Mycobacterium tuberculosis in Wenzhou[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2023, 53(4): 305-310.
Abstract：Objective: To analyze by whole genome sequencing (WGS) the drug resistance of multi-drug resistant/rifampicin-resistant Mycobacterium tuberculosis (MDR/RR-MTB) in Wenzhou in order to provide reference for the prevention and treatment of drug-resistant tuberculosis. Methods: The strains and clinical data of 54 patients with MDR/RR-TB treated in Wenzhou Central Hospital from January 2021 to September 2022 were collected and WGS was performed. The drug resistance of strains to 15 kinds of anti-tuberculosis drugs was analyzed. Simultaneously, a string diagram of bacterial resistance and a heat map were used to visualize drug resistance spectrum of all strains and pre-XDR-MTB/XDR-MTB strains, respectively. Results: Of 54 patients,75.93% were male and 50.00% over 45 years old; Wenzhou local residents accounted for 83.33%, non-fixed occupation 92.59%, and retreatment accounted for 40.74% of the treatment types. There was significant difference in sex, age, household registration and occupation (P<0.05), but there was no significant difference in the type of treatment (P>0.05). The drug resistance rate of 54 strains to drugs ranking from high to low was rifampicin (100.00%, 54/54), isoniazid (83.33%, 45/54), streptomycin (50.00%, 27/54), ethambutol (38.89%, 21/54), pyrazinamide (35.19%, 19/54), fluoroquinolones (24.07%, 13/54), prothionamide (24.07%, 13/54), and kanamycin (9.26%, 5/54), amikacin (9.26%, 5/54), capreomycin (9.26%, 5/54), para-aminosalicylic acid (7.41%, 4/54), linezolide (1.85%, 1/54), did not produce resistance to bedaquiline, cycloserine and chlorfazimine. A total of 65 types of gene mutations were detected, and mutations were most common in katG_S315T (77.78%, 35/45), rpoB_S450L (48.15%, 26/54), embB_M306V (52.38%, 11/21),rpsL_K43R (77.78%, 21/27), and gyrA_D94G (30.77%, 4/13). There were 3 XDR-TB strains (5.56%, 3/54) and 10 Pre-XDR-TB strains (18.52%, 10/54) were detected. Conclusion: Most of the MDR/RR-TB patients in Wenzhou are local middle-aged and elderly men with no fixed occupation, and the proportion of retreatment is high. The resistance rate of the strains to first-line anti-tuberculosis drugs, fluoroquinolones and prothionamide is high, mainly to katG, rpoB, embB, rpsL, pncA and gyrA gene mutations, but low to berdaquinoline, linezolid, cycloserine and chlorfazimine. The proportion of Pre-XDR-TB in MDR/RR-TB is high, so clinical treatment should refer to the results of drug sensitivity test for the sake of reasonable drug use.
