Early efficacy of individual regimens containing bedaquiline in patients with drug resistant tuberculosis

Objective:To evaluate early efficacy of sputum conversion within 6 months of individual regimens containing bedaquiline in patients with drug resistant tuberculosis.Methods:We conducted a retrospective study among patients with drug resistant tuberculosis who were receiving individual regimens containing bedaquiline.The primary outcome was sputum conversion of both smear and culture within 6 months of treatment.We used medical records of drug resistant tuberculosis patients from January 2020 to December 2021.The study was conducted at Dr.Soetomo Hospital,Indonesia from August to October 2022.Results:In this study,44 eligible drug resistant tuberculosis patients were initiated on regimens containing bedaquiline.There were 52.3%males and the median age was 45.5 years.The rates of previous treatment(70.5%)and lung cavity(36.4%)were high.The most common companion drugs included clofazimine,cycloserine,levofloxacin,and linezolid.Sputum smear and culture conversion was seen in 79.4%and 82.1%at the 2nd month,respectively.More than 97%patients had smear and culture conversion at the end of 6 months.Conclusions:Among drug resistant tuberculosis patients,individual regimens containing bedaquiline were associated with high rates of smear and culture conversion at the end of 6 months.Early efficacy of regimens containing bedaquiline can be used to predict cure rate at the end of treatment.

Community-based management versus traditional hospitalization in treatment of drug-resistant tuberculosis:a systematic review and meta-analysis

Background:Multidrug drug resistant Tuberculosis(MDR-TB)and extensively drug resistant Tuberculosis(XDR-TB)have emerged as significant public health threats worldwide.This systematic review and meta-analysis aimed to investigate the effects of community-based treatment to traditional hospitalization in improving treatment success rates among MDR-TB and XDR-TB patients in the 27 MDR-TB High burden countries(HBC).Methods:We searched PubMed,Cochrane,Lancet,Web of Science,International Journal of Tuberculosis and Lung Disease,and Centre for Reviews and Dissemination(CRD)for studies on community-based treatment and traditional hospitalization and MDR-TB and XDR-TB from the 27 MDR-TB HBC.Data on treatment success and failure rates were extracted from retrospective and prospective cohort studies,and a case control study.Sensitivity analysis,subgroup analyses,and meta-regression analysis were used to explore bias and potential sources of heterogeneity.Results:The final sample included 16 studies involving 3344 patients from nine countries;Bangladesh,China,Ethiopia,Kenya,India,South Africa,Philippines,Russia,and Uzbekistan.Based on a random-effects model,we observed a higher treatment success rate in community-based treatment(Point estimate=0.68,95%CI:0.59 to 0.76,p<0.01)compared to traditional hospitalization(Point estimate=0.57,95%CI:0.44 to 0.69,p<0.01).A lower treatment failure rate was observed in community-based treatment 7%(Point estimate=0.07,95%CI:0.03 to 0.10;p<0.01)compared to traditional hospitalization(Point estimate=0.188,95%CI:0.10 to 0.28;p<0.01).In the subgroup analysis,studies without HIV co-infected patients,directly observed therapy short course-plus(DOTS-Plus)implemented throughout therapy,treatment duration>18 months,and regimen with drugs>5 reported higher treatment success rate.In the meta-regression model,age of patients,adverse events,treatment duration,and lost to follow up explains some of the heterogeneity of treatment effects between studies.Conclusion:Community-based management improved treatment outcomes.A mix of interventions with DOTSPlus throughout therapy and treatment duration>18 months as well as strategies in place for lost to follow up and adverse events should be considered in MDR-TB and XDR-TB interventions,as they influenced positively,treatment success.

Treatment outcomes and adverse drug reactions among patients with drug-resistant tuberculosis receiving all-oral,long-term regimens:First record viewing report from Pakistan

Objective:To assess the effectiveness and adverse drug reactions of all-oral regimens for patients with multidrug-resistant tuberculosis.Methods:This retrospective study was conducted at 10 Programmatic Management of Drug Resistant Tuberculosis sites in Punjab province of Pakistan.Patients receiving treatment for drug resistant tuberculosis from July 2019 to December 2020 with at least interim result i.e.6th month culture conversion or final outcomes(cured,complete,lost to follow-up,failure,death)available,were included in the study.Data was extracted from electronic data management system.For the reporting and management of adverse drug events,active tuberculosis drug safety monitoring and management was implemented across all sites.All the data was analyzed using SPSS version 22.Results:Out of 947 drug resistant tuberculosis patients included in this study,579(68%)of the patients had final outcomes available.Of these,384(67.9%)successfully completed their treatment.Out of 368(32%)patients who had their interim results available,all had their 6th month culture negative.Combining new medications was thought to result in serious adverse outcomes such as QT prolongation.However,this study did not record any severe adverse events among patients.Conclusions:All-oral regimens formulation guided by overall treatment effectiveness resulted in treatment outcomes comparable to those obtained with traditional injectable treatment.

Clinical efficacy and computed tomography diagnostic value of bedaquiline-containing regimens in the treatment of drug-resistant pulmonary tuberculosis

Objective:This study investigated the clinical efficacy of bedaquilinecontaining regimens in the treatment of drug-resistant pulmonary tuberculosis and the diagnostic value of computed tomography(CT).Methods:We retrospectively analyzed the clinical diagnosis,treatment,and CT imaging data of patients with drug-resistant pulmonary tuberculosis treated in Wenzhou Central Hospital from 1 January to 31 December 2022.According to whether the treatment regimen contained bedaquiline,the patients were divided into an observation group(bedaquiline tablets t background regimen)and a control group(background regimen).The clinical efficacy and pulmonary CT changes before and after treatment were analyzed in both groups.Results:After 24 weeks of treatment,there was no statistically significant difference in the white blood cell count or concentrations of hemoglobin,alanine aminotransferase,serum albumin,or creatinine between the two groups(t=0.71,0.93,0.05,0.18,and 0.08,respectively;p>0.05).After 4,8,and 12 weeks of treatment,there was no statistically significant difference in the sputum culture-negative conversion rate between the two groups(χ^(2)=2.67,0.48,and 1.82,respectively;p>0.05).At 24 weeks of treatment,the sputum culture-negative conversion rate in the observation group reached 100%,which was significantly higher than that in the control group(χ^(2)=3.97,p<0.05).The effective absorption rates on chest imaging in the two groups of patients at 12 weeks were 83.33% and 57.89%,respectively.At 24 weeks of treatment,the effective absorption rates were 88.00% and 65.85% in the two groups,with a statistically significant difference(χ^(2)=3.98;p<0.05).There were significant differences in cavity absorption at 24 weeks(χ^(2)=4.33,p<0.05)and 48 weeks after treatment(χ^(2)=10.63,p<0.05).Conclusion:The addition of bedaquiline to the background regimen improved the sputum culture-negative conversion rate and chest imaging effective rate.Patients achieved good results at the end of the 24-week treatment period.

Detection of mutation in embB gene of Mycobacterium tuberculosis from clinical isolates of tuberculous patients in China by means of reverse-dot blot hybridization

The relationship between embB mutation of Mycobacterium tuberculosis and ethambutol （EMB） resistance of the clinical isolates of tuberculous patients in China was investigated by reversedot blot hybridization （RDBH） in addition to evaluating the clinical value with application of PCR-RDBH technique to detect EMB resistance. In the present study, the genotypes of the 258 bp fragments of embB genes from 196 clinical isolates of M. tuberculosis were analysed with RDBH and DNA sequencing. It was demonstrated that 60 out of 91 phenotypically EMB-resistant isolates （65.9%） showed 5 types of missense mutations at codon 306 of embB gene, resulting in the replacement of the Met residue of the wild type strain with Val, Ile or Leu residues. In these mutations, the GTP mutation （38/91, 41.8% ） and the ATA mutation （16/91, 17.6% ） were the most encountered genotypes. The embB mutation at codon 306 could also be found in 69 isolates of phenotypically EMB-sensitive but resistant to other anti-tuberculous drugs, but no such gene mutation could be found in 36 strains of drug-sensitive isolates. Meanwhile, the concordance with the results of DNA sequencing fcr one wide-type probe and 5 probes for specific mutations was 100%. It was concluded that the EMB-resistance occurring in most M. tuberculosis is due to appearance of embB mutation at codon 306, and the PCR-RDBH assay was proved to be a rapid, simple and reliable method for the detection of gene mutations, which might be a good alternative for the drug-resistance screening.

Multidrug-resistant Tuberculosis Burden among the New Tuberculosis Patients in Zhejiang Province： An Observational Study, 2009-2013

Background：Screening on multidrug-resistant tuberculosis （MDR-TB） has been limited to the serious TB subpopulations excluding the new TB patients.This study aimed to examine MDR-TB burden among the new TB patients.Methods：We conducted a study in Zhejiang Province during 2009-2013 to screen for MDR-TB patients among the low MDR-TB risk patients and five subpopulations of high MDR-TB risk patients.The number,prevalence,and trend of MDR-TB were compared while the logistic regression model was used to examine risk factors related to MDR-TB.Results：A total of 200 and 791 MDR-TB cases were,respectively,identified from the 9830 new TB cases and 2372 high-risk suspects who took MDR-TB screening from 2009 to 2013.The MDR-TB rates went down in both of the new TB patients and five MDR-TB high-risk groups over the study time,but the percentage of MDR-TB patients identified from the new TB patients in all diagnosed MDR-TB cases kept stable from 28.3% in 2011 to 27.0% in 2012 to 26.0% in 2013.Conclusions：The study indicated that MDR-TB burden among new TB patients was high,thus screening for MDR-TB among the new TB patients should be recommended in China as well as in the similar situation worldwide.

Prunella vulgaris L. extract improves cellular immunity in MDR-TB challenged rats

Objective： To study the effect of the extract of Prunella vulgaris L. on multiple drugs resistant bacillus tuberculosis （MDR-TB）. Methods： Experimental animal model in rats was induced by MDR-TB. Normal group model group and Prunella vulgaris L. group were set up. The contents of IFN-7, IL-4, IL-10 and IL-12 were examined by ELISA. Their genome mRNAs were extracted, the target genes were amplified by PCR. RT-PCR was used to detect the mRNA levels of them. Results： The content of IFN-q, of the extract of Prunella vulgaris L. group was 1.98±0.67 pg/ml, IL-4 was 6.47±1.46 pg/ml, IL-10 was 12.13±3.43 pg/ml and IL-12 was 3.02±0.86 pg/ml. Compared with the model group, Prunella vulgaris L. group was notable difference in serum IFN-γ, IL-12 and IL-10 （P〈0.05）. The mRNA levels of IFN-γ, IL-12 increased and IL-10 decreased obviously, the differences were quite significant （P〈0.05）, but IL-4 had no obvious change. Conclusion： The extract of Prunella vulgaris L. can enhance the cellar immunological function in rats from up-regulation of the level of genetic transcription, accordingly provide the theory basis of healing of tuberculosis with it.

MprAB双组分系统基因在耐药MTB中的表达水平分析

目的:分析结核分枝杆菌(Mycobacterium tuberculosis,MTB)临床分离株对4种一线抗结核药物的耐药情况以及结核分枝杆菌双组份系统Mpr AB与MTB耐药性的相关性。方法:收集本地区确诊的结核病患者痰液标本,分离培养得到的MTB菌株进行4种一线抗结核药物异烟肼(Isoniazid,H)、利福平(Rifampicin,R)、链霉素(Streptomycin,S)和乙胺丁醇(Ethambutol,E)的耐药性检测并比较双组分系统Mpr AB编码基因(Mpr A、Mpr B)在MTB标准株(H37Rv)、耐异烟肼(H-MTB)、耐利福平(R-MTB)、耐链霉素(S-MTB)、耐乙胺丁醇(E-MTB)和耐多药(Multi-drug Resistant MTB,M-MTB)菌株中的表达量。结果:分离培养得到72株分枝杆菌,对一种抗结核药物具有耐药性的有19株(H 8株、S 5株、R 3株、E 3株),耐药率为26.39%,对二种及以上耐药的有6株,耐多药率为8.33%(6/72)。Mpr A在H37Rv、H-MTB、R-MTB、S-MTB、E-MTB、M-MTB各组相对表达量分别为:1.12±0.07、3.34±0.42、4.16±0.46、3.09±0.24、2.27±0.18、8.43±0.63,Mpr B在各组相对表达量分别为:5.71±0.59、2.42±0.22、1.47±0.11、2.28±0.23、2.09±0.15、0.54±0.03。Mpr A和Mpr B基因在H37Rv与各耐药组之间比较差异有统计学意义(p0.05),Mpr A和Mpr B基因在各单耐药组与MDR组之间比较有统计学意义,而Mpr A和Mpr B基因在各单耐药组间比较均无统计学意义。结论:Mpr AB双组分系统与MTB耐药性的产生有一定的相关性。