Prolonged use of bedaquiline in two patients with pulmonary extensively drug-resistant tuberculosis: Two case reports

BACKGROUND Bedaquiline is among the prioritized drugs recommended by the World Health Organization for the treatment of extensively drug-resistant tuberculosis(XDRTB).Many patients have not achieved better clinical improvement after bedaquiline is stopped at 24 wk.However,there is no recommendation or guideline on bedaquiline administration beyond 24 wk,which is an important consideration when balancing the benefit of prognosis for XDR-TB against the uncertain safety concerning the newer antibiotics.CASE SUMMARY This paper reported 2 patients with XDR-TB(a female of 58 years of age and a female of 18 years of age)who received bedaquiline for 36 wk,as local experience to be shared.The 2 cases had negative cultures after 24 wk of treatment,but lung imaging was still positive.After discussion among experts,the consensus was made to bedaquiline prolongation by another 12 wk.The 36-wk prolonged use of bedaquiline in both cases achieved a favorable response without increasing the risk of cardiac events or new safety signals.CONCLUSION Longer regimen,including 36-wk bedaquiline treatment,might be an option for patients with XDR-TB.More studies are needed to explore the effectiveness and safety of prolonged use of bedaquiline for 36 wk vs standard 24 wk in the treatment of multidrug-resistant/XDR-TB or to investigate further the biomarkers and criteria indicative for extension of bedaquline to facilitate clinical use of thisnovel drug.

Bedaquiline-containing regimens in patients with pulmonary multidrug-resistant tuberculosis in China:focus on the safety

Background:World Health Organization recommends countries introducing new drug and short treatment regimen for drug resistant tuberculosis(DR-TB)should develop and implement a system for active pharmacovigilance that allows for detection,reporting and management of adverse events.The aim of the study is to evaluate the frequency and severity of adverse events(AEs)of bedaquiline-containing regimen in a cohort of Chinese patients with multidrug-resistant(MDR)/extensively drug-resistant(XDR)-TB based on active drug safety monitoring(aDSM)system of New Drug Introduction and Protection Program(NDIP).

The China tuberculosis clinical trials consortium network:a model for international TB clinical trials capacity building

Background:With the second largest tuberculosis(TB)burden globally,China is committed to actively engage in international TB clinical trials to contribute to global TB research.However,lack of research capacity among local sites has been identified as a barrier.Main text:The China Tuberculosis Clinical Trials Consortium(CTCTC)was initiated by Beijing Chest Hospital with investment from the US National Institutes of Health and technical support from Family Health International 360 in 2013,as a nationwide collaborative clinical trial network to strengthen selected clinical site research capacity and attract TB clinical trials.The program aims to:1)recruit leading hospitals that care for TB patients;2)conduct on-site assessment to identify capacity gaps and needs for improvement;3)design and deliver capacity building activities;4)attract and deliver high quality results for TB clinical trials.A total of 24 sites have joined CTCTC,covering 20 provinces in China.Twenty-two sites have been accredited by the National Medical Products Administration(NMPA)to be qualified to conduct TB clinical trials.The onsite assessment,extensive trainings among the CTCTC sites and young investigators have resulted in better understanding and improvement of the site capacity in conducting TB clinical trials.The establishment and growth of the CTCTC network has benefited from the good leadership,effective international cooperation and local commitment.Issues in human resources,regulatory environment and sustainability have been challenging the network from continuing growth.Clinical researchers have full-time clinical responsibilities in China and it is thus important to build a cadre of other human resources to assist.The regulatory environment is becoming friendlier in China to introduce international clinical trials to the CTCTC network.Conclusions:The CTCTC,with mature management structure and sustainable development model,which are distilled five key lessons for other developing countries or investigators of interest.They are the respectively using assessment-based approach to design tailored training package,understanding the availability of clinical researchers,providing solutions to maintain sustainability,understanding local regulatory environments and working with an international organization with local on-site team,respectively.Although,the experiences and capacity of China’s TB hospitals in conducting clinical research vary.Considerable efforts to continue building the capacity are still needed,although the gap is smaller for a few top-tier hospitals.