Novel 6-Month Treatment for Drug-Resistant Tuberculosis,United States

The US Food and Drug Administration approved a 6-month regimen of pretomanid, bedaquiline, and linezolid for extensively drug-resistant or multidrug-intolerant tuberculosis after a trial in South Africa demonstrated 90% effectiveness 6 months posttreatment. We report on a patient who completed the regimen using a lower linezolid dose.     

Bedaquiline and delamanid in the treatment of multidrug-resistant tuberculosis: Promising but challenging

Improving treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) is partly hampered by inadequate effective antitubercular agents. Development of bedaquiline and delamanid has potentially changed the treatment landscape for MDR-TB. This review provides an update on the progress of these novel antitubercular agents. We review published studies aimed at evaluating clinical efficacy and effectiveness of bedaquiline and delamanid. Five prospective clinical studies and seven retrospective studies on bedaquiline showed that patients treated with a bedaquiline-containing regimen had a high culture conversion rate ranging from 65 to 100% and a satisfactory treatment outcome. The combined use with linezolid might add to the effectiveness of bedaquiline. Controversies about bedaquiline resistance are discussed. Three clinical trials have reported outcomes on delamanid and showed that introducing delamanid to a background regimen improved culture conversion rate at 2 months from 29.6% to more than 40%. A higher favorable treatment rate was also observed among patients who received delamanid for more than 6 months, but about a quarter of patients defaulted in the control group. Seven retrospective studies were summarized and found a treatment benefit as well. More reliable evidence from randomized clinical trials reporting on the treatment outcomes is needed urgently to support a strong recommendation for the use of delamanid. Advances in the combined use of bedaquiline and delamanid are also reviewed, and the combination may be well tolerated but requires electrocardiograph monitoring.     

An overview of new antitubercular drugs,drug candidates,and their targets

The causative agent of tuberculosis (TB), Mycobacterium tuberculosis and more recently totally drug-resistant strains of M. tuberculosis, display unique mechanisms to survive in the host. A four-drug treatment regimen was introduced 40 years ago but the emergence of multidrug-resistance and more recently TDR necessitates the identification of new targets and drugs for the cure of M. tuberculosis infection. The current efforts in the drug development process are insufficient to completely eradicate the TB epidemic. For almost five decades the TB drug development process remained stagnant. The last 10 years have made sudden progress giving some new and highly promising drugs including bedaquiline, delamanid, and pretomanid. Many of the candidates are repurposed compounds, which were developed to treat other infections but later, exhibited anti-TB properties also. Each class of drug has a specific target and a definite mode of action. These targets are either involved in cell wall biosynthesis, protein synthesis, DNA/RNA synthesis, or metabolism. This review discusses recent progress in the discovery of newly developed and Food and Drug Administration approved drugs as well as repurposed drugs, their targets, mode of action, drug-target interactions, and their structure-activity relationship.     

2020—2022年安徽省胸科医院抗结核药物使用情况分析

目的 统计2020—2022年安徽省胸科医院抗结核药物使用情况并分析其变化趋势,为规范其合理应用提供一定参考。方法 对2020年1月—2022年12月安徽省胸科医院抗结核药物销售金额、用药频度（DDDs）、日均费用（DDC）以及金额排序/DDDs排序比（B/A）等进行统计分析。结果 2020—2022医院抗结核药物销售金额总体呈增长趋势,新型类抗结核药物销售金额2022年较2020年增幅333.43%,注射类降幅72.68%,贝达喹啉、注射用利奈唑胺、环丝氨酸、氯法齐明排名靠前,其中贝达喹啉连续2年销售金额排名第1位。DDDs每年总体基本稳定,排名靠前的为一线口服类抗结核药物：异烟肼、乙胺丁醇、吡嗪酰胺、利福平,2022年DDDs贝达喹啉排名第1位。利奈唑胺等40.00%抗结核药物DDC降低。每年一线口服类抗结核药物B/A均大于1,2022年B/A＞0.9的药物占比达60.00%。结论 安徽省胸科医院抗结核药物使用基本合理,仍然需要加强监督管理,减小耐药结核发生率。     

Preliminary Favorable Outcome for Medically and Surgically Managed Extensively Drug-Resistant Tuberculosis,France, 2009–2014

We report 20 cases of extensively drug-resistant tuberculosis managed in France. Treatment was individualized and included bedaquiline and linezolid for most patients and surgery in 8 patients. At last follow-up (22 months), 19 patients had achieved conversion from positive to negative on culture testing. These promising results of comprehensive management obtained in a small series deserve confirmation.     

含贝达喹啉的联合治疗方案治疗耐多药肺结核患者的长期效果及不良反应

目的探讨含贝达喹啉的联合治疗方案治疗耐多药肺结核患者的长期效果及不良反应。方法2018年6月至2020年1月,对我院采用个体化抗结核药物治疗的30例耐多药肺结核患者(对照组)与采用个体化抗结核药物联合贝达喹啉治疗的30例耐多药肺结核患者(观察组)的临床资料进行回顾性分析,比较两组的治疗效果。结果观察组的病灶吸收率、空洞闭合率、痰菌转阴率均显著高于对照组(P<0.05)。治疗后,观察组的IL-6、CRP、PCT水平均显著低于对照组(P<0.05)。治疗后,观察组的生理、心理、环境、社会关系评分均显著高于对照组(P<0.05)。两组的不良反应总发生率无显著差异(P>0.05)。结论贝达喹啉用于耐多药肺结核患者抗结核药物治疗中,可增强抗结核作用,更加有效地促使结核病灶吸收、肺部空洞闭合、痰菌转阴,减轻机体炎症反应,有利于提升患者生活质量,且未增多不良反应,用药安全性可靠。     

结核分枝杆菌贝达喹啉和氯法齐明耐药及其交叉耐药机制研究进展

目前,全球结核病耐药现象严重,给结核病的防控工作带来了极大的困难与挑战,并亟需新型抗结核药物来阻止耐药结核病的蔓延.贝达喹啉和氯法齐明分别是世界卫生组织推荐的A组和B组核心抗结核药物,主要用于耐多药结核病的治疗且疗效较好.但近年来贝达喹啉和氯法齐明耐药的现象也时有报道,且二者存在交叉耐药的情况.本文综述了与结核分枝杆菌...     

Synthetic investigational new drugs for the treatment of tuberculosis

Introduction: Tuberculosis (TB) is a major global health concern. And while there are treatments already on the market, there is a demand for new drugs that are effective and safe against Mycobacterium tuberculosis, which reduce the number of drugs and the duration of treatment in both drug-susceptible TB and multidrug-resistant TB (MDR-TB).

Area covered: This review covers promising novel investigational TB drugs that are currently under development. Specifically, the authors review the efficacy of novel agents for the treatment of TB in preclinical, phase I and phase II clinical trials. The authors also review the safety and tolerability profiles of these drugs.

Expert opinion: Bedaquiline and delamanid are the most promising novel drugs for the treatment of MDR-TB, each having high efficacy and tolerability. However, the best regimen for achieving better outcomes and reducing adverse drug reactions remains to be determined, with safety concerns regarding cardiac events due to QT prolongation still to be addressed. Pretomanid is a novel drug that potentially shortens the duration of treatment in both drug-susceptible and drug-resistant TB in combination with moxifloxacin and pyrazinamide. Linezolid shows marked efficacy in the treatment of MDR-TB and extensively drug-resistant TB (XDR-TB), but the drug is known to cause significant adverse drug reactions, including peripheral neuropathy, optic neuropathy and myelosuppression. These adverse reactions must be considered prior to prescribing long-term usage of this drug.     

Current therapies for the treatment of multidrug-resistant tuberculosis in children in India

Introduction: Multidrug-resistant tuberculosis (MDR-TB) is a serious life threatening condition affecting children as well as adults worldwide. Timely diagnosis and effective treatment, both of which are complex in children, are the prerogatives for a favorable outcome.

Areas covered: This review covers epidemiology, treatment regimen and duration, newer drugs and adverse events in children with MDR-TB. Special note has been made of epidemiology and principles of treatment followed in Indian children.

Expert opinion: High index of suspicion is essential for diagnosing childhood MDR-TB. If there is high probability, a child can be diagnosed as presumptive MDR-TB and started on empiric treatment in consultation with experts. However, every effort should be made to confirm the diagnosis. Backbone of an effective MDR-TB regimen consists of four 2nd line anti-TB drugs plus pyrazinamide; duration being 18–24 months. The newer drugs delamanid and bedaquiline can be used in younger children if no other alternatives are available after consultation with experts. Wider availability of these drugs should be ensured for benefit to all concerned. More research is required for development of new and repurposed drugs to combat MDR-TB. Children need to be included in clinical trials for such life-saving drugs, so that nobody is denied the benefits.     

Leveraging Advances in Tuberculosis Diagnosis and Treatment to Address Nontuberculous Mycobacterial Disease

The nontuberculous mycobacteria (NTM), defined as any mycobacterial pathogen other than Mycobacterium tuberculosis or Mycobacterium leprae, are a diverse group of pathogens that collectively cause a substantive but often unappreciated worldwide burden of illness. Although NTMs may cause illness similar to M. tuberculosis, these pathogens generally do not respond to classic tuberculosis (TB) drug regimens, resulting in misdiagnosis and poor treatment, particularly in resource-poor settings. Although a few high-quality epidemiologic surveys have been made on the topic, existing evidence suggests that NTM-associated disease is much more common than previously thought: more common than TB in the industrialized world and likely increasing in prevalence globally. Despite this evidence, these organisms remain markedly understudied, and few international grants support basic science and clinical research. Here we suggest that the considerable efforts in developing new treatments and diagnostics for TB can be harnessed in the fight against NTM-associated illnesses.