摘要
目的:通过全基因组测序(WGS)分析温州市耐多药/利福平耐药结核分枝杆菌(MDR/RR-MTB)的耐药情况,为耐药结核病的防治提供参考依据。方法:收集2021年1月至2022年9月温州市中心医院收治的54例MDR/RR-TB患者的菌株与临床资料,对菌株进行WGS。分析菌株对15种抗结核药物的耐药情况,同时绘制耐药情况弦图,以及准广泛耐药结核(Pre-XDR-TB)与广泛耐药结核(XDR-TB)菌株耐药情况热图。结果:54例患者中,男性占75.93%,>45岁占50.00%,温州本地户籍占83.33%,无固定职业占92.59%,治疗类型中复治占40.74%。患者性别(男、女)间,年龄(<30、30~45、>45岁)间,户籍(本地、外地)间,职业(无固定职业及体力劳动者、非体力劳动者)间比较差异有统计学意义(P<0.05),初治与复治比例比较差异无统计学意义(P>0.05)。54株菌株对药物的耐药率从高到低依次为利福平(100.00%,54/54)、异烟肼(83.33%,45/54)、链霉素(50.00%,27/54)、乙胺丁醇(38.89%,21/54)、吡嗪酰胺(35.19%,19/54)、氟喹诺酮类(24.07%,13/54)、丙硫异烟胺(24.07%,13/54)、卡那霉素(9.26%,5/54)、阿米卡星(9.26%,5/54)、卷曲霉素(9.26%,5/54)、对氨基水杨酸(7.41%,4/54)、利奈唑胺(1.85%,1/54);对贝达喹啉、环丝氨酸、氯法齐明未产生耐药。共检出65种基因突变类型,以kat G_S315T(35株,占77.78%)、rpo B_S450L(26株,占48.15%)、embB_M306V(11株,占52.38%)、rps L_K43R(21株,占77.78%)、gyr A_D94G(4株,占30.77%)突变多见。检出3株(5.56%)XDR-TB菌株和10株(18.52%)Pre-XDR-TB菌株。结论:温州市MDR/RR-TB患者以本地、中老年、无固定职业、男性为主,复治比例较高。菌株对一线抗结核药物、氟喹诺酮类药物、丙硫异烟胺的耐药率较高,以kat G、rpo B、emb B、rps L、pnc A、gyr A基因突变为主,对贝达喹啉、利奈唑胺、环丝氨酸、氯法齐明等耐药率较低。MDR/RR-TB中Pre-XDR-TB比例较高。
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.
作者
吴联朋
徐克
何贵清
WU Lianpeng;XU Ke;HE Guiqing(Department of Clinical Laboratory Medicine,the Dingli Clinical Institute of Wenzhou Medical University,Wenzhou Central Hospital,Wenzhou 325000,China;Key Laboratory for Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou,Wenzhou 325000,China;Department of Infectious Disease,the Dingli Clinical Institute of Wenzhou Medical University,Wenzhou Central Hospital,Wenzhou 325000,China)
出处
《温州医科大学学报》
CAS
2023年第4期305-310,共6页
Journal of Wenzhou Medical University
基金
浙江省基础公益研究计划项目(LGF20H010003)
温州市基础性科研项目(Y20210722)。
关键词
结核分枝杆菌
耐药性
全基因组测序
基因突变
Mycobacterium tuberculosis
drug resistance
whole genome sequencing
genetic mutation
