Research progress on the drug action and resistance mechanism in Mycobacterium tuberculosis

Tuberculosis(TB)is a chronic infectious disease caused by Mycobacterium Tuberculosis(MTB).It is the second largest single cause of death besides novel coronavirus pneumonia.Along with the abuse of antibiotics and extensive use of anti-tuberculosis drugs,multidrug-resistant(MDR)TB,drug-resistant(XDR)TB and totally drug-resistant(TDR)TB became obstacles to the tuberculosis eradication worldwide.According to the World Health Organization(WHO)statistics,China is not only a high burden tuberculosis country in the world,but also a country with a serious epidemic of MDR.Traditional drugs fail to meet the needs of tuberculosis control.Therefore,it is urgent to find new targets of anti-tuberculosis drugs and develop new anti-tuberculosis drugs.Hence,this paper systematically summarizes the mechanism of traditional and newly developed anti-tuberculosis drugs,in which stressing the research progress of drug resistance mechanisms.This work provides us with new insights of new anti-tuberculosis drug developments,and may contribute to a reduction in the harm that tuberculosis brings to society.

Meta‑analysis of influencing factors associating with treatment outcome of multidrug resistant tuberculosis

Objective:To systematically review the influencing factors of the treatment outcome of multidrug-resistant pulmonary tuberculosis and provide reference for the prevention and treatment of multidrug-resistant pulmonary tuberculosis.Method:Case control studies on the factors influencing the treatment outcome of multidrug-resistant pulmonary tuberculosis in Chinese databases(CNKI,VIP,Wanfang,Sinomed)and English databases(Pubmed,Web of science,Medline,Embase,Scopus)were searched and collected by computer.The search period was from the establishment of the database to January 2023.After screening and quality evaluation,RevMan5.4 was used for meta-analysis.Result:Totally 18 articles were ultimately included,with a sample size of 7328 people.The results showed that retreatment,complications,adverse reactions,and gender were related to the treatment outcome of multidrug-resistant pulmonary tuberculosis.The OR values and 95%CI of each factor were 0.22(0.17-0.29),0.38(0.32-0.46),0.27(0.17-0.44),and 0.43(0.33-0.56),respectively.Conclusion:Complications,retreatment,adverse reactions,and male gender are effective risk factors for the treatment outcome of multidrug-resistant pulmonary tuberculosis.In clinical practice,more targeted measures are needed for different types of patients.Due to the limitations of the number of studies,the above conclusions require more research to support them.

Prevalence of Adverse Drug Reactions to Second Line Anti Tuberculosis Drugs in Nigeria: A Cross-Sectional Study

Introduction: Multidrug resistant tuberculosis (MDR-TB) is treated with second line antituberculosis drugs. These drugs are notorious for inflicting serious adverse drug reactions (ADRs), which many studies have shown causes a wide range of economic and health problems including death. Aim: The study examined the prevalence of ADRs, associated risk factors, socio-demographic association and outcomes among patients treated for MDR-TB at a comprehensive tuberculosis treatment center in Nigeria. Method: The study was conducted at the Government Chest Hospital, Jericho, Ibadan. We applied a retrospective assessment of patient treatment data and ADRs reports stored at the study site from March 2013 and February 2016. Subsequently, a prospective study of ADRs was conducted on patients admitted into the same hospital. Causality relationship between the drugs and the reported ADRs was determined with a specially validated tool. The outcomes assessed include recovery from the ADRs, death and permanent deafness from the ADRs. Extracted data were analyzed using SPSS version 22.0. Risk Ratio was calculated for the influence of risk factors for adverse drug reactions. Logistic regression was performed to test for the strength of relationships between risk factors and incidence of ADRs among patients. Result: Almost all the participants in this study reported adverse drug reaction [99% (118/119)]. However, ototoxicity was the most prevalent ADR (35.3%), followed by electrolyte imbalance (12.6%), gastrointestinal track (10.1%) and psychiatric disorders (10.1%). Being older than 35 years and HIV negative or having a healthy BMI were not significant risk factors for developing ADRs. Duration of ADR above one month was significantly associated with the outcome of ADR. Conclusion: Ototoxicity, electrolyte imbalance, psychiatric disorders and gastrointestinal tract problems were the most frequently reported ADRs. Healthcare providers, government and donor agencies supporting the treatment should ensure that hearing aids and other forms of support are readily made available for the affected patients.

上海市耐多药结核病患者经济负担研究

目的基于上海市近年结核病诊疗费用减免政策,探索耐多药结核病(multidrug resistant tuberculosis,MDR-TB)患者疾病经济负担及其影响因素,为优化MDR-TB诊疗费用减免政策和综合管理模式提供依据。方法收集上海市2017—2019年确诊MDR-TB患者情况和诊疗费用减免情况数据,开展针对疾病经济负担的问卷调查,建立涵盖患者人口和社会经济情况、临床特征、疾病经济负担和诊疗费用减免情况数据库,明确患者疾病经济负担和灾难性卫生支出(catastrophic health expenditure)发生情况。以多元线性回归法分析可能影响患者疾病经济负担的因素,以多因素logistic回归法分析不同比例下灾难性卫生支出发生的影响因素。结果196例纳入研究分析的MDR-TB患者平均年龄为(44±16)岁,男性139例(占70.9%),上海户籍占46.4%,49%的患者为家庭主要劳动力。治疗期间,患者自付诊疗费用中位数为4.0(四分位数区间2.0~6.5)万元。113例患者获得减免诊疗,减免费用中位数为2.6(四分位数区间1.3~4.9)万元。若自付费用占家庭年收入的40%及以上,有47.8%的患者会发生灾难性支出;若不考虑减免政策,有59.8%的患者发生灾难性卫生支出。上海户籍(OR=0.3,95%CI为0.1~1.0)、更低家庭收入水平(P_(trend)=0.002)、医疗保险类型[(农村合作医疗保险/外来人口综合保险(OR=13.3,95%CI为1.0~171.2),无医疗保险(OR=17.5,95%CI为2.7~113.0)]和既往结核病治疗史(OR=3.3,95%CI为1.1~10.0)可能影响灾难性卫生支出的发生。结论上海市MDR-TB患者的自付诊疗费用较高。医疗保障力度较小和家庭经济情况不佳的患者更易发生高额自付费用,导致灾难性卫生支出。上海市MDR-TB诊疗费用减免政策有效降低了患者的经济负担。

Sirturo(Bedaquiline):The first new anti tubercular drug in decades

Tuberculosis(TB) is an infection caused by Mycobacterium tuberculosis and is one of the world's deadliest diseases. Multidrug resistant TB(MDR-TB) is a serious form of TB and it implies resistance for at least two essential first-line agents like, Isoniazid and Rifampicin. The US Food and Drug Administration(FDA) granted accelerated approval to Janseen Therapeutics "Sirturo(Bedaquiline)", a diarylquinoline anti mycobacterial drug on December 28, 2012 as part of combination therapy in adults(≥ 18 years) to treat MDR-TB when other alternatives are not available. The FDA also granted Sirturo fast track designation, priority review and orphanproduct designation. Bedaquiline inhibits mycobacterial ATP(adenosine 5'-triphosphate) synthase, an enzyme that is essential for the generation of energy in Mycobacterium tuberculosis.