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 im...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.展开更多
Background:China is the second highest pulmonary tuberculosis(PTB)burden country worldwide.However,retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs.The cure rate(a...Background:China is the second highest pulmonary tuberculosis(PTB)burden country worldwide.However,retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs.The cure rate(approximately 50.0–73.3%)and management of retreatment of PTB in China needs to be improved.Qinbudan decoction has been widely used to treat PTB in China since the 1960s.Previously clinical studies have shown that the Qinbudan tablet(QBDT)promoted sputum-culture negative conversion and lesion absorption.However,powerful evidence from a randomized controlled clinical trial is lacking.Therefore,the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB.Methods:We conducted a multicenter,randomized,double-blind,placebo-controlled clinical trial in China.People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013.The treatment group received an anti-TB regimen and QBDT,and the control group was administered an anti-TB regimen plus placebo.Anti-TB treatment options included isoniazid,rifampicin,pyrazinamide,ethambutol,streptomycin for 2 months(2HRZES),followed by isoniazid,rifampicin,ethambutol for 6 months(6HRE),daily for 8 months.Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method.Secondary outcomes included lung lesion absorption and cavity closure.Adverse events and reactions were observed after treatment.A structured questionnaire was used to record demographic information and clinical symptoms of all subjects.Data analysis was performed by SPSS 25.0 software in the full analysis set(FAS)population.Results:One hundred eighty-one cases of retreatment PTB were randomly divided into two groups:the placebo group(88 cases)and the QBDT group(93 cases).A total of 166 patients completed the trial and 15 patients lost to follow-up.The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences(79.6%vs 69.3%;rate difference=0.10,95%confidence interval(CI):-0.02–0.23;F=2.48,P=0.12)after treatment.A significant 16.6%increase in lesion absorption was observed in the QBDT group when compared with the placebo group(67.7%vs 51.1%;rate difference=0.17,95%CI:0.02–0.31;χ2=5.56,P=0.02).The intervention and placebo group did not differ in terms of cavity closure(25.5%vs 21.1%;rate difference=0.04,95%CI:-0.21–0.12;χ2=0.27,P=0.60).Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting.Conclusions:No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen.However,QBDT as an adjunct therapy significantly promoted lesion absorption,thereby reducing lung injury due to Mycobacterium tuberculosis infection.Trial registration:This trial is registered at ClinicalTrials.gov,NCT02313610.展开更多
文摘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.
基金This study was supported by the Eleventh Five-Year Support Project of the Ministry of Science and Technology from Ministry of Public Health of China(2010ZX09101-107)。
文摘Background:China is the second highest pulmonary tuberculosis(PTB)burden country worldwide.However,retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs.The cure rate(approximately 50.0–73.3%)and management of retreatment of PTB in China needs to be improved.Qinbudan decoction has been widely used to treat PTB in China since the 1960s.Previously clinical studies have shown that the Qinbudan tablet(QBDT)promoted sputum-culture negative conversion and lesion absorption.However,powerful evidence from a randomized controlled clinical trial is lacking.Therefore,the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB.Methods:We conducted a multicenter,randomized,double-blind,placebo-controlled clinical trial in China.People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013.The treatment group received an anti-TB regimen and QBDT,and the control group was administered an anti-TB regimen plus placebo.Anti-TB treatment options included isoniazid,rifampicin,pyrazinamide,ethambutol,streptomycin for 2 months(2HRZES),followed by isoniazid,rifampicin,ethambutol for 6 months(6HRE),daily for 8 months.Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method.Secondary outcomes included lung lesion absorption and cavity closure.Adverse events and reactions were observed after treatment.A structured questionnaire was used to record demographic information and clinical symptoms of all subjects.Data analysis was performed by SPSS 25.0 software in the full analysis set(FAS)population.Results:One hundred eighty-one cases of retreatment PTB were randomly divided into two groups:the placebo group(88 cases)and the QBDT group(93 cases).A total of 166 patients completed the trial and 15 patients lost to follow-up.The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences(79.6%vs 69.3%;rate difference=0.10,95%confidence interval(CI):-0.02–0.23;F=2.48,P=0.12)after treatment.A significant 16.6%increase in lesion absorption was observed in the QBDT group when compared with the placebo group(67.7%vs 51.1%;rate difference=0.17,95%CI:0.02–0.31;χ2=5.56,P=0.02).The intervention and placebo group did not differ in terms of cavity closure(25.5%vs 21.1%;rate difference=0.04,95%CI:-0.21–0.12;χ2=0.27,P=0.60).Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting.Conclusions:No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen.However,QBDT as an adjunct therapy significantly promoted lesion absorption,thereby reducing lung injury due to Mycobacterium tuberculosis infection.Trial registration:This trial is registered at ClinicalTrials.gov,NCT02313610.
