Serum IL-1β and IL-18 correlate with ESR and CRP in multidrug-resistant tuberculosis patients

Dear Editor： The emergence of multidrug-resistant tuberculosis （MDR-TB） is bringing new challenges. MDR-TB is caused by Mycobacterium tuberculosis （M. tuberculosis） that is resistant to isoniazid and rifampicin, with or with- out resistance to other anti-tuberculosis drugs. Approximately 450,000 people developed MDR-TB worldwide in 2012 and an estimated 170,000 people died from the disease. Bacterial burden is not strictly corre- lated with disease progression, and several hallmarks of severe tuberculosis suggest that insufficiently controlled inflammation plays an important role in pathogenesis.

Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in China

Objective This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline(BR)and the conventional treatment regimen(CR,not containing Bedaquiline)for the treatment of adults with multidrug-resistant tuberculosis(MDR-TB)in China.Methods A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten years.The model parameter data were synthesized from the literature,the national TB surveillance information system,and consultation with experts.The incremental cost-effectiveness ratio(ICER)of BR vs.CR was determined.Results BR(vs.CR)had a higher sputum culture conversion rate and cure rate and prevented many premature deaths(decreased by 12.8%),thereby obtaining more quality-adjusted life years(QALYs)(increased by 2.31 years).The per capita cost in BR was as high as 138,000 yuan,roughly double that of CR.The ICER for BR was 33,700 yuan/QALY,which was lower than China's 1×per capita Gross Domestic Product(GDP)in 2020(72,400 yuan).Conclusion BR is shown to be cost effective.When the unit price of Bedaquiline reaches or falls below57.21 yuan per unit,BR is expected to be the dominant strategy in China over CR.

Risk Factors for Multidrug-Resistant Tuberculosis and Characteristics of Cases: A Case-Control Study of Patients Attending ALERT General Hospital in Addis Ababa, Ethiopia

Background:Tuberculosis remains a major public-health problem in the world, despite several efforts to improve case identification and treatment. Particularly multidrug-resistant tuberculosis is becoming a major threat to tuberculosis control programs in Ethiopia which seriously threatens the control and prevention efforts and is associated with both high death rates and treatment costs. Methods: A case-control study was conducted to assess risk factors and characteristics of MDR-TB cases at ALERT Hospital, Addis Ababa, Ethiopia, where cases were 167 MDR-TB patients, while controls were newly diagnosed and bacteriologically confirmed pulmonary TB cases of similar number, who were matched by sex and age of 5-years interval. Results: The socio-demographic characteristics of the participants indicated that majority (53.3%) were males and 46.7% females;a little over half of cases (55.1%) were in the age group 26 - 45 years, whereas 46.7% of controls were in this age group. According to the multivariable logistic regression analysis, previous history of hospital admission was the only factor that was identified as predictor which increased risk to develop MDR-TB by almost twenty times (AOR = 19.5;95% CI: 9.17 - 41.62) and P-value of <0.05. All other studied factor such as being unemployed, family size, having member of household member with TB, and history of visiting hospital in past 12 months etc., didn’t show any statistically significant association. Conclusion: The study identified previous history of hospital admission as independent predictors for the occurrence of MDR-TB, while other studied variables didn’t show any strong association. The findings added to the pool of knowledge emphasizing the need for instituting strong infection control practice at health care facilities to prevent nosocomial transmission of MDR-TB.

Screening outcomes of household contacts of multidrug-resistant tuberculosis patients in Peshawar,Pakistan

Objective:To assess the profile of TB/multidrug-resistant TB(MDR-TB) among household contacts of MDR-TB patients.Methods:Close contacts of MDR-TB patients were traced in the cross-sectional study.Different clinical,radiological and bacteriological were performed to rule out the evidence of TB/MDR-TB.Results:Between January 2012 and December 2012,a total of 200 index MDR-TB patients were initiated on MDR-TB treatment,out of which home visit and contacts screening were conducted for 154 index cases.Of 610 contacts who could be studied,41(17.4%) were diagnosed with MDR-TB and 10(4.2%) had TB.The most common symptoms observed were cough,chest pain and fever.Conclusions:The high incidence of MDR-TB among close contacts emphasize the need for effective contact screening programme of index MDR-TB cases in order to cut the chain of transmission of this disease.

Case of bronchoesophageal fistula with gastric perforation due to multidrug-resistant tuberculosis

Gastric perforation and tuberculous bronchoesophageal fistula(TBEF) are very rare complications of extrapulmonary tuberculosis(TB). We present a case of pulmonary TB with TBEF and gastric perforation caused by a multidrug-resistant tuberculosis strain in a nonacquired immune deficiency syndrome male patient.The patient underwent total gastrectomy with Rouxen-Y end-to-side esophagojejunostomy and feeding jejunostomy during intravenous treatment with anti-TB medication, and esophageal reconstruction with colonic interposition and jejunocolostomy were performed successfully after a full course of anti-TB medication.Though recent therapies for TBEF have favored medication, patients with severe stenosis or perforation require surgery and medication with anti-TB drugs basedupon adequate culture and drug susceptibility testing.

Multidrug-Resistant Tuberculosis in the Democratic Republic of Congo: Analysis of Continuous Surveillance Data from 2007 to 2016

Background: For countries with limited resources such as the Democratic Republic of the Congo (DRC), the diagnosis of Multidrug-resistant tuberculosis (MDR-TB) is still insufficient. The MDR-TB identification is done primarily among at-risk groups. The knowledge of the true extent of the MDR-TB remains a major challenge. This study tries to determine the proportion of MDR-TB in each group of presumptive MDR-TB patients and to identify some associated factors. Methods: This is an analysis of the DRC surveillance between 2007 and 2016. The proportions were expressed in Percentage. The logistic regression permits to identify the associated factors with the RR-/MDR-TB with adjusted Odds-ratio and 95% CI. Significance defined as p ≤ 0.05. Results: Overall, 83% (5407/6512) of the MDR-TB presumptive cases had each a TB test. 86.5% (4676/5407) had each a culture and drug sensitive testing (DST) on solid medium, and 24.3% (1312/5407) had performed an Xpert MTB/RIF test. The proportion of those with at least one first-line drug resistance was 59.3% [95% CI 57.2 - 61.4] among which 50.1%, [95% CI 47.9 - 52.3] for the isoniazid, 45.6% [95% CI 43.4 - 47.8] for the rifampicin, 49.9% [95% CI 47.8 - 52.1] for ethambutol and 35.8% [95% CI 33.7 - 37.9] for streptomycin. The confirmation of MDR-TB was 42.8% [95% CI 38.4 - 47.8]. Combining both tests, the proportion of RR-/MDR-TB was 49.6% [95% CI 47.9 - 51.4] for all presumptives. This proportion was 60.0% for failures, 40.7% for relapses and 34.7% for defaulters. Associated factors with the diagnosis of MDR-TB were: aged less than 35 years;prior treatment failure;defaulters;the delay between the collection of sputum and the test completion. Conclusion: The proportion of RR-/MDR-TB among the presumptives has been higher than those estimated generally. The National tuberculosis programme (NTP) should improve patient follow-up to reduce TB treatment failures and defaulting. Moreover, while increasing the use of molecular tests, they should reduce sample delivery times when they use culture and DST concomitantly.

Sensorineural Hearing Loss in Multidrug-Resistant Tuberculosis Patients in Kinshasa (Democratic Republic of Congo): Prospective Cohort Study of Therapeutic Regimen with Aminoglycoside versus Bedaquiline

Context: Multidrug-resistant tuberculosis (MDR-TB) remains a major public health problem in developing countries such as the Democratic Republic of Congo (DRC), which continues to face the emergence of MDR-TB cases. Because of the ototoxic effects of AGs, the World Health Organization (WHO) has recommended the introduction of the bedaquiline regimen. However, very few data are available regarding the susceptibility of bedaquiline to induce hearing loss, hence the present study set out to compare the AG-based regimen and the bedaquiline-based regimen in the occurrence of hearing loss in MDR-TB patients. Methods: This is a prospective multicenter cohort study that included 335 MDR-TB patients, performed in Kinshasa (DRC) during the period from January 2020 to January 2021. Sociodemographic, clinical, biological and audiometric data were analyzed using Stata 17. Repeated-measures analysis of variance was used to compare changes in the degree of hearing loss over time between the two groups of patients on AG and bedaquiline regimens. The double-difference method was estimated using regression with fixed-effects. A p value < 0.05 was considered the threshold for statistical significance. Results: The degree of hearing loss was similar between the two groups at the first month [AGs (28 dB) vs BDQ (30 dB);p = 0.298]. At six months, the mean degree of hearing loss was significantly greater in the aminoglycoside regimen group [AGs (60.5 dB) vs BDQ (44 dB);p < 0.001]. The double difference was significant, with a greater increase in hearing loss in the AGs group (diff-in-diff 18.3;p < 0.001). After adjustment for age and serum albumin, the group receiving the AG-based regimen had a 2-point greater worsening than those with bedaquiline at the sixth month (diff-in-diff 19.8;p Conclusion: Hearing loss is frequent with both treatment regimens, but more marked with the Aminoglycoside-based regimen. Thus, bedaquiline should also benefit for audiometric monitoring in future MDR-TB patients.

Determinants of the Sensorineural Hearing Loss in Patients with Multidrug-Resistant Tuberculosis in Kinshasa (Democratic Republic of the Congo): A Prospective Cohort Study

Background: The onset of the hearing loss is a major challenge during the treatment of multidrug-resistant tuberculosis (MDR-TB). Aminoglycoside-based regimens, to a lesser extent based on bedaquiline, induce ototoxic sensorineural hearing loss. Research on risk factors is essential to enable high-risk individuals to benefit from preventive measures in settings with limited resources. Objective: This study aimed to assess the determinants of the hearing loss in patients with MDR-TB. Methods: This prospective multicenter cohort study included 337 patients with MDR-TB. It was performed in Kinshasa (Democratic Republic of the Congo) between January 2020 and January 2021. Sociodemographic, clinical, biological, therapeutic, and audiometric data were exported and analyzed using Stata 17 and MedCalc. The fixed-effect linear regression panel model was used to assess the degree of the hearing loss over time according to the following covariates: therapeutic regimen (aminoglycosides, bedaquiline, or alternate), stage of chronic kidney disease (CKD), age at inclusion, body mass index, serum albumin level, HIV status, alcohol intake, hypertension, and hemoglobin level. The Hausman test was used to select between fixed- and random-effect estimators. The threshold for statistical significance was set at p Result: A total of 236 patients (70%) received an aminoglycoside-based regimen, 61 (18%) received a bedaquiline-based regimen, and 40 (12%) received aminoglycosides relayed by bedaquiline. The frequency of the hearing loss increased from 62% to 96.3% within six months for all therapeutic regimens. The Hearing loss worsened, with moderate (72.4%) and profound (16%) deafness being predominant. An Exposure to the treatment for more than one month (β coeff: 27.695, Se: 0.793, p β coeff: 6.102, Se: 1.779, p β coeff: 5.610, Se: 1.682, p = 0.001), and an eGFR β coeff: 6.730, Se: 2.70, p = 0.013) were the independent risk factors associated with the hearing loss in patients with MDR-TB. Conclusions: The Hearing loss was more prevalent and worsened during the treatment of the patients with MDR-TB. An Exposure for more than one month, AG-based regimens, advanced age, hypoalbuminemia, and CKD have emerged as the main determinants of the worsening of the hearing loss.

Drug Resistance Pattern in Pulmonary Tuberculosis Patients and Risk Factors Associated with Multi-Drug Resistant Tuberculosis

Introduction: Anti-tuberculosis drug resistance is a major problem in tuberculosis (TB) control programme, particularly multi-drug resistance TB (MDR-TB) in Nepal. Drug resistance is difficult to treat due to its associated cost and side effects. The objective of this study was to assess the drug resistance pattern and assess risk factor associated with MDR-TB among pulmonary tuberculosis patients attending National Tuberculosis Center. Methodology: The comparative cross sectional study was conducted at National Tuberculosis Center during August 2015 to February 2015. Early morning sputum samples were collected from pulmonary tuberculosis suspected patients and subjected to Ziehl-Neelsen staining and fluorochrome staining and culture on Lowenstein-Jensen (LJ) medium. Drug Susceptibility test was performed on culture positive isolates by using proportion method. Univariate and multivariate analysis was computed to assess the risk factors of MDR-TB. Results: Out of 223 sputum samples, 105 were fluorochrome staining positive, 85 were ZN staining positive and 102 were culture positive. Out of 102 culture positive isolates, 37.2% were resistance to any four anti-TB drugs. 11 (28.9%) were initial drug resistance and 28 (43.7%) were acquired drug resistance. The overall prevalence of MDR-TB was 11.7%, of which 2 (5.3%) were initial MDR-TB and 10 (15.6%) were acquired MDR-TB. Univariate and multivariate analysis showed female were significantly associated (P = 0.05) with MDR-TB. Conclusion: Drug resistance TB particularly MDR-TB is high. The most common resistance pattern observed in this study was resistance to both isoniazid and rifampicin. Female were found to be associated with MDR-TB. Thus, early diagnosis of TB and provision of culture and DST are crucial in order to combat the threat of DR-TB.

Diagnostic Evaluation of GeneXpert MTB/RIF Assay for the Detection of Rifampicin Resistant Mycobacterium tuberculosis among Pulmonary Tuberculosis Patients in Bangladesh

Background: The emergence of multidrug resistant tuberculosis (MDR-TB) and extensively drug- resistant tuberculosis (XDR-TB) has highlighted the need for early accurate detection and drug susceptibility. Objective: The purpose of the present study was to evaluate the accuracy of GeneX-pert MTB/RIF assay for the detection of Mycobacterium tuberculosis and rifampicin resistance. Methodology: This cross sectional study was done in the Department of Microbiology at Sir Salimullah Medical College, Dhaka and National Institute of Chest Disease & Hospital (NIDCH), Dhaka during the period of January 2014 to December 2014 for a period of 1 (one) year. Sputum samples from suspected MDR-TB patients were collected by purposive sampling technique from OPD of Sir Salimullah Medical College (SSMC) and NIDCH. Microscopy, liquid culture in liquid MGIT 960 media and GeneXpert MTB/RIF were done for MTB diagnosis and detection of rifampicin resistance. MGIT 960 media were also used for determination of drug resistance. Result: Liquid culture yielded higher growth (68%) from 100 samples while GeneXpert MTB assay showed similar result (67% positive and 33% negative). Drug susceptibility test in MGIT 960 media showed that out of 68 positive cases Rifampicin resistant cases were 15 (22.05%) whereas GeneXpert MTB assay detected 14 (20.89%) were Rifampicin resistant out of 67 MTB positive samples. When compared to liquid culture the calculated sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of GeneXpert MTB were 98.52%, 100%, 96.96%, 100% and 99%. Conclusion: GeneXpert MTB/RIF assay is high detection rate of pulmonary tuberculosis and multidrug resistant tuberculosis.

Unbiased Multirresistance Prevalences in Real Testing Practices? An Intuitive Correcting Approach Applied to Tuberculosis in Portugal

Background: Antibiotics resistance threats Tuberculosis control, being crucial to work on unbiased MDR-TB images. The decision of testing is clinical, non-random, raising extrapolation problems. Aim: To evince and describe non-random testing practices;develop and apply a coherent and intuitive method for estimating global corrected resistance prevalences (2000-2009). Methods: A quantitative approach upon National Tuberculosis Database was undertaken, to assess testing potential predicting factors. Different factors structures in tested and non-tested cases were characterized (regarding socio-demographic and clinical variables), through binary logistic regressions. Estimated multirresistance prevalences were corrected using the essayed model. Results: Only 32% of cases had been tested, where MDR-TB prevalence was 2.38%. All factors influenced the practice of testing (p < 0.05). Corrected resistance estimates in non-tested ranged 1.96% - 2.71%, and the global weighted average found ranged 2.07% - 2.51%, depending on the chosen strata structure. Conclusions: MDR-TB prevalence representation must consider patients’ characteristics influencing testing. The correction method improved prevalences interpretation substantially;corrected and conventional values were close, because tested and non-tested had similar structures. But in other settings or health problems, correcting such estimates can make a relevant difference.

Treatment Initiation among Patients with Multidrug Resistant Tuberculosis in Bhopal District, India

Revised national tuberculosis control programme in India has limited co-hort-wise information about what happens to patients diagnosed with multidrug resistant TB (MDR-TB). We determined the pre-treatment loss to follow-up (non-initiation of treatment by programme within 6 months of diagnosis) and time from diagnosis to treatment initiation in Bhopal district, central India (2014). Pre-treatment loss to follow-up was 13% (0.95 CI: 7%, 23%), not significantly different from the national estimates (18%) and median time to initiate treatment was seven days, lower than that reported elsewhere in the country. Bhopal was performing well with reference to time to treatment initiation in programmatic settings.

First Line Anti-Tuberculosis Drugs Resistance Patterns of <i>Mycobacterium tuberculosis</i>Isolates from Newly Diagnosed Cases of Tuberculosis

Introduction: Tuberculosis is a major cause of mortality and morbidity world-wide. Anti-tuberculosis drugs have been used for many decades but resistance to them is now widespread. Globally 5% of tuberculosis cases and in India 3% among new TB cases. This study was planned to know the pattern of first line anti-tuberculosis drug resistance in south Gujarat, Surat region in newly diagnosed patients of tuberculosis. Material and Methods: 350 samples were processed for homogenisation and concentration using 4% NAOH-2.9% trisodium citrate. Processed samples were inoculated in liquid medium that is MGIT (Mycobacterial growth indicator tube). Positive samples for M. tbwere processed further for first line anti-tuberculosis drugs sensitivity testing (DST). Reading was taken by using MicroMGIT system. Result: Out of 350 samples 59 (17%) were positive samples, of which 48 (13%) were M. tb and 11 (3%) were non tuberculous mycobacteria. Out of 48 samples 2% (1 isolate) was resistant to isoniazid and Rifampicin while 2% were monoresistant to isoniazide, 2% monoresistant to streptomycin. No rifampicin monoresistant was detected. Conclusion: Such study may help in control of tuberculosis at regional and national level which would in turn help in planning of measures to control Multi-drug resistance tuberculosis. Continuous surveillance should be applied to know the periodic changing patterns and trend in Drug resistant tuberculosis.

The Role of Pyridoxine in the Prevention and Treatment of Neuropathy and Neurotoxicity Associated with Rifampicin-Resistant Tuberculosis Treatment Regimens: A Topic Review

Rifampicin-resistant tuberculosis (RR-TB) is a global public health problem caused by mycobacterium tuberculosis resistant to Rifampicin. Drug-induced peripheral neuropathy and neurotoxicity are well-known adverse effects of treatment regimens that cause significant morbidity. Pyridoxine is often added to treatment regimens for the prevention and/or treatment of these side effects. The basis and effectiveness of this practice are unclear. We conducted a systematic review to evaluate the effectiveness of pyridoxine in preventing and/or treating neuropathy and neurotoxicity associated with RR-TB treatment. We included studies with patients with RR-TB who experienced neuropathy or neurotoxicity attributed to RR-TB regimens and were given pyridoxine. Our findings showed contradicting evidence on the use of pyridoxine for preventing or treating neurotoxicity due to cycloserine in the treatment of RR-TB. Moreover, pyridoxine did not have a protective effect against neuropathy and/or neurotoxicity caused by other RR-TB regimens that do not contain isoniazid. In conclusion, we found that withdrawing or withholding medications such as linezolid, cycloserine, thioamides, fluoroquinolones, and ethambutol, implicated in causing neuropathy or neurotoxicity was more effective than using pyridoxine to stop the progression of symptoms, and in some instances, led to their reversal over time.

Evaluation of <i>In-Vitro</i>Anti-Tuberculosis Activity of <i>Tetrapleura tetraptera</i>Crude and Fractions on Multidrug Resistant <i>Mycobacterium tuberculosis</i>

The management, control and elimination of tuberculosis (TB) have been difficult with the advent of HIV and cases of multidrug resistant (MDR-TB) tuberculosis. The cases of multidrug resistance to rifampicin and isoniazid pose greater challenges on first line and second line drugs to eliminate TB. The study is aimed at establishing anti-tuberculosis activity of Tetrapleura tetraptera against Mycobacterium tuberculosis and MDR-TB and the phytochemical present. The leaves of Tetrapleura tetraptera were collected, weighed, dried and pulverized to powder. The pulverized leaves of Tetrapleura tetraptera were subjected to 70% methanol extraction and screened for phytochemical. The crude extract was further purified into fractions using silica gel and thin layer chromatography techniques. M. tuberculosis and MDR-TB were obtained from positive acid fast bacilli sputa of TB patients and confirmed using GeneXpert to differentiate genotypic drug susceptible M. tuberculosis and MDR-TB. The sputa were digested using sodium hydroxide-cysteine technique and cultured in Middlebrook 7H9. The crude extract and fractions were screened for anti-tuberculosis activity using tetrazolium microtitre plate assay. The results showed that Tetrapleura tetraptera crude had activities against M. tuberculosis at 7.4 ± 0 mg/ml and 27.5 ± 0 mg/ml for MDR-TB. One of the fractions inhibited the growth of M. tuberculosis at 0.24 ± 0 mg/ml and MDR-TB at 0.89 ± 0 mg/ml. The phytochemical screened includes tannins, alkaloids, saponins, flavonoids, phenols and resins. T. tetraptra possesses anti-tuberculosis potential at low concentration on MDR-TB and can be a lead compound in drug development for the treatment of tuberculosis and multidrug resistant tuberculosis.

Prevalence of Mycobacterium tuberculosis Strains Isolated from Both Pulmonary and Extra Pulmonary Samples and Their Resistance to Rifampicin: A Study from Kolkata and Surrounding Suburbs

Tuberculosis (TB) is one of the major causes of morbidity and mortality worldwide. In India, nearly 1.8 million new cases of TB are reported annually, which accounts for a fifth of new cases in the world—greater than in any other country. Anti-tubercular drugs (ATDs) have been used for decades, and widespread resistance to them is a very serious public health concern in any part of the world. Aim of this study was to determine the prevalence of Rifampicin (the first line Anti-TB drug) resistance among both pulmonary and extra-pulmonary samples tested positive for Mycobacterium tuberculosis and thereby predict the prevalence of Multi-drug resistant (MDR) tuberculosis in Kolkata and its Suburban regions. All 331 randomly collected clinical samples (both Pulmonary and Extra Pulmonary) were initially screened by Zeihl-Neelsen AFB staining followed by culture on BacT/Alert 3D system and on Lowenstein-Jensen medium and the positive samples were subjected to detection of Mycobacterium tuberculosis complex (MTBC) and simultaneous analysis of Rifampicin resistance by Xpert MTB/RIF assay. Out of the 51 (15.40%) culture positive samples, 13.7% of pulmonary samples and 9.09% of extra-pulmonary samples were Rifampicin resistant. The prevalence of Rifampicin resistant TB in our study is high and the possible reasons can be mixing of new as well as retreatment cases and smaller sample size but, yet it can help Government and public health regulatory bodies to formulate adequate strategies to fight against drug resistant tuberculosis, especially in this part of the world.

Efficacy and Safety of Bufei Jiedu Granules in Treating Multidrug-Resistant Pulmonary Tuberculosis:A Multi-center,Double-Blinded and Randomized Controlled Trial

Objective: To assess the efficacy and safety of Bufei Jiedu(BFJD) Granules as adjuvant therapy for patients with multidrug-resistant pulmonary tuberculosis(MDR-PTB). Methods: A large-scale, multi-center, double-blinded, and randomized controlled trial was conducted in 18 sentinel hospitals in China from December 2012 to December 2016. A total of 312 MDR-PTB patients were randomly assigned to BFJD Granules or placebo groups(1:1) using a stratified randomization method, which both received the long-course chemotherapy regimen for 18 months(6 Am-Lfx-P-Z-Pto, 12 Lfx-P-Z-Pto). Meanwhile, patients in both groups also received BFJD Granules or placebo twice a day for a total of 18 months, respectively. The primary outcome was cure rate. The secondary outcomes included time to sputum-culture conversion, changes in lung cavities and quality of life(QoL) of patients. Adverse reactions were monitored during and after the trial. Results: A total of 216 cases completed the trial, 111 in the BFJD Granules group and 105 in the placebo group. BFJD Granules, as adjuvant treatment, increased the cure rate by 13.6% at the end of treatment, compared with the placebo(58.4% vs. 44.8%, P=0.02), and accelerated the median time to sputum-culture conversion(5 months vs. 11 months). The cavity closure rate of the BFJD Granules group(50.6%, 43/85) was higher than that of the placebo group(32.1%, 26/81;P=0.02) in patients who completed the treatment. At the end of the intensive treatment, according to the 36-item Short Form, the BFJD Granules significantly improved physical functioning, general health, and vitality of patients relative to the placebo group(all P<0.01). Overall, the death rates in the two groups were not significantly different;5.1%(8/156) in the BFJD Granules group and 2.6%(4/156) in the placebo group. Conclusions: Supplementing BFJD Granules with the long-course chemotherapy regimen significantly increased the cure rate and cavity closure rate, and rapidly improved QoL of patients with MDR-PTB(Registration No. ChiCTR-TRC-12002850)

Immunotherapy using IL-2 and GM-CSF is a potential treatment for multidrug-resistant Mycobacterium tuberculosis

This study investigated the therapeutic effects of interleukin （IL）-2 and granulocyte-macrophage colony-stimulating factor （GM-CSF） co-administrated with antibacterial agents isoniazid （INH） and rifampin （RIF） to treat a mouse model of tuberculo- sis （TB） infection. A drug-susceptible TB strain, H37Rv was used to infect mice and the effectiveness of IL-2 and GM-CSF was initially evaluated based on survival rate, bacterial counts in lungs and spleens and the pathological condition of the lungs. Next, the therapeutic effect of the immunotherapy regimen was assessed in multidrug-resistant strain OB35-infected mice. In the H37Rv infection model, 1L-2 and GM-CSF monotherapies reduced bacterial numbers in the lungs by 0.82 （P〈0.01） and 0.58 （P〈0.05） lg colony-forming units （CFU）, respectively, and in the spleens by 1.42 （P〈0.01） and 1.22 （P〈0.01） lg CFU, re- spectively, compared with the untreated group. Mice receiving immunotherapy developed fewer lesions in the lungs compared with mice receiving antibacterial therapy alone. In the OB35 infection model, immunotherapy with either cytokine resulted in a significant reduction of bacterial load in the lungs and spleens and less severe lesions in the lungs compared with the untreated or antibacterial therapy treated mice. Notably, mice receiving immunotherapy with both cytokines had a 30% survival rate which was higher than that in other treated groups, and had significantly less CFUs in the lungs and spleens （1.02 and 1.34 lg CFU） compared with antibacterial therapy alone （P〈0.01）. This study demonstrated that immunotherapy with both IL-2 and GM-CSF may be useful to treat multidrug resistant tuberculosis （MDR-TB）.

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).

Treatment outcomes for multidrug-resistant tuberculosis under DOTS-Plus:a systematic review and meta-analysis of published studies

Background:Anti-tuberculosis drug resistance is a major public health problem that threatens the progress made in tuberculosis care and control worldwide.Treatment success rates of multidrug-resistant tuberculosis(MDR-TB)is a key issue that cannot be ignored.There is a paucity of evidence that assessed studies on the treatment of MDR-TB,which focus on the effectiveness of the directly observed treatment,short-course(DOTS)-Plus program.Therefore,it is crucial to assess and summarize the overall treatment outcomes for MDR-TB patients enrolled in the DOTS-Plus program in recent years.The purpose of this study was to thus assess and summarize the available evidence for MDR-TB treatment outcomes under DOTS-Plus.Methods:A systematic review and meta-analysis of published literature was conducted.Original studies were identified using the databases MEDLINE®/PubMed®,Hinari,and Google Scholar.Heterogeneity across studies was assessed using the Cochran’s Q test and I2 statistic.Pooled estimates of treatment outcomes were computed using the random effect model.Results:Based on the 14 observational studies included in the meta-analysis,it was determined that 5047 patients reported treatment outcomes.Of these,the pooled prevalence,63.5%(95%CI:58.4-68.5%)successfully completed full treatment(cured or treatment completed)with a pooled cure rate of 55.6%,whereas 12.6%(95%CI:9.0-16.2%)of the patients died,14.2%(95%CI:11.6-16.8%)defaulted from therapy,and 7.6%(95%CI:5.6-9.7%)failed therapy.Overall 35.4%(95%CI:30-40.8%)of patients had unsuccessful treatment outcomes.An unsatisfactorily high percentage 43%(95%CI:32-54%)of unsuccessful treatment outcomes was observed among patients who were enrolled in standardized treatment regimens.Conclusion:This study revealed that patients with MDR-TB exhibited a very low treatment success rate compared to the World Health Organization 2015 target of at least 75 to 90%.The high default rate observed by conducting this literature review could possibly explain the spread of the MDR-TB strain in various populations.A better treatment success rate was observed among patients in individualized treatment regimens than in standardized ones.Conducting further individual-based meta-analysis is recommended to identify potential factors for defaulting treatment using large-scale and multi-center studies.