Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-spe...Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.展开更多
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,...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.展开更多
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 adu...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.展开更多
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 multi...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.展开更多
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. B...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.展开更多
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...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.展开更多
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 threa...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.展开更多
We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. ...We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment;the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on antiretroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted.展开更多
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 ...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.展开更多
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,ra...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.展开更多
Introduction: The emergency of Mycobacterium tuberculosis resistant to the first line drug reduced access possibility to second line drugs for appropriate treatment and required for urgent action especially in le Demo...Introduction: The emergency of Mycobacterium tuberculosis resistant to the first line drug reduced access possibility to second line drugs for appropriate treatment and required for urgent action especially in le Democratic Republic of Congo (DRC), which counts among the highest tuberculosis (TB) burden countries in Africa. Objective: To present prevalence and describe multidrug-resistant tuberculosis cases in North-Kivu Province identified by using Genexpert technology. Methods: We conducted an observational prospective study on multidrug-resistant tuberculosis (MDR-TB) cases in North-Kivu Province, DRC from 2017 to 2018. All cases of MDR-TB identified by Genexpert MTB/ RIB were included in this series. Result: Of 15,544 tuberculosis cases registered during the study period, 19 cases of MDR-TB were identified. 57.9% was male, 89.5% was retreatment cases and 5.3% was coinfection HIV/TB cases. Conclusion: This new molecular technology diagnostic facilitates multidrug-resistance tuberculosis detection and improves the reporting of data lack.展开更多
Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly devel...Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.展开更多
This study examined the clinical,sociodemographic and treatment-related parameters influencing the therapeutic response to multidrug-resistant(MDR)tuberculosis(TB)treatment in pediatric patients.This multicenter retro...This study examined the clinical,sociodemographic and treatment-related parameters influencing the therapeutic response to multidrug-resistant(MDR)tuberculosis(TB)treatment in pediatric patients.This multicenter retrospective cross-sectional study was conducted in the programmatic management of drug-resistant tuberculosis sites in Khyber Pakhtunkhwa,Pakistan.Basic character-istics,treatment regimens and outcomes were collected from the TB registries.Out of the 450 patients analyzed,79.1%had successful treatment results,achieving the WHO aim of>75%.Similar to previous studies,this study reported a 5.3%death rate and a 5.6%loss to follow-up.Multivariate analysis showed that no history of prior TB treatment was significantly associated with unfavorable outcomes(ad-justed OR:3.1,95%CI:1.9–5.1,P<0.001).Patients on a specific second-line longer treatment regimen(Lfx,Bdq,Cs,Lzd,Cfz,B6)had higher odds of unsuccessful outcomes(adjusted OR:2.0,P=0.009).Furthermore,patients on shorter treatment regimens were substantially more likely to experience unsuccessful outcomes.The study emphasizes the difficulty in treating children with MDR-TB and the importance of creating individualized treatment programs that take each patient’s medical history and resistance profile into ac-count.Although shorter regimens and newer medications seem promising,further research is required to verify their efficacy.展开更多
Objective:To analyze the risk factors associated with multidrug-resistant tuberculosis(MDR-TB)as a first national survey in Indonesia.Methods:This national coverage cross-sectional study was conducted from 2017 to 201...Objective:To analyze the risk factors associated with multidrug-resistant tuberculosis(MDR-TB)as a first national survey in Indonesia.Methods:This national coverage cross-sectional study was conducted from 2017 to 2018.The study subjects were selected using a multi-stage probability random sampling method.MDR-TB is tuberculosis caused by bacteria resistant to at least isoniazid and rifampicin.The dependent variable was MDR-TB.Independent variables included age,sex,education,employment status,place of residence,history of living with TB patients,and the number of household members.Univariate and multivariate logistic regression models were used to analyze the risk factors associated with MDR-TB.All the data were analyzed using STATA V.14.0(Stata Corp LLC,College Station,TX).Results:This study found the MDR rate was 109/3234(3.4%)among positive pulmonary TB patients.More than twice as many patients had MDR re-treatment(74/3234,2.3%),compared to 35/3234(1.1%)who had new TB diagnoses or were getting initial treatment.After adjusting for employment status,individuals with a prior history of tuberculosis treatment were found to have significantly higher odds of developing MDR-TB,with an odds ratio of 7.22(95%CI 3.87-13.44).Conclusions:Increasing attention should be paid to these patients to prevent MDR-TB,and MDR-TB transmission is an urgent challenge for controlling TB worldwide.Early detection of MDR-TB is a critical part of TB control programs.展开更多
Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world ...Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world scenarios at the Haji Hospital,Surabaya.Methods:We conducted a case-control study from June to December 2024.MDR-TB and DS-TB patients were classified into case and control groups,respectively.We used the World Health Organization’s Quality of Life Brief(WHOQOL-BREF)instrument and Patient Health Questionnaire-9(PHQ-9)to assess QoL and depression levels,respectively.Multivariate analysis was used to analyze factors associated with QoL of patients with MDR-TB.Results:Forty-one patients with MDR-TB and 43 with DS-TB were enrolled in the study.A mean score for all domains(physical,psychological,social relationship,environmental)and total mean score of WHOQOL-BREF was significantly lower in MDR-TB than those with DS-TB(P<0.05).The prevalence of depression and the mean score of PHQ-9 were significantly higher in MDR-TB than in DS-TB(P<0.05).PHQ-9 negatively correlates with the WHOQOL-BREF score(r=-0.502,P<0.05)among MDR-TB patients.MDR-TB patients with depression were significantly associated with low QoL in the physical(OR 3.611;95%CI 2.393-6.951;P=0.029),psychological(OR 1.672;95%CI 1.179-5.941;P=0.021),social relationship(OR 2.586;95%CI 1.611-2.909;P=0.014),and environmental domains(OR 1.926;95%CI 1.047-2.147;P=0.048).Conclusions:MDR-TB patients had worse QoL than DS-TB.Those with depression were associated with low QoL.Strategies that identify and tackle alterations in the QoL for MDR-TB patients are necessary during TB treatment.展开更多
Tuberculosis(TB)remains the leading infectious disease globally,with 1.25 million deaths and 10.8 million new cases in 2023,including 400,000 rifampin-resistant/multidrug-resistant TB(RR/MDR-TB)cases.RR/MDR-TB account...Tuberculosis(TB)remains the leading infectious disease globally,with 1.25 million deaths and 10.8 million new cases in 2023,including 400,000 rifampin-resistant/multidrug-resistant TB(RR/MDR-TB)cases.RR/MDR-TB accounts for 15–20%of TB-related deaths and poses significant economic and treatment challenges due to low cure rates(68%)and high costs.The heterogeneity of Mycobacterium tuberculosis infections complicates therapy,requiring prolonged regimens and multidrug combinations.Advances in treatment include repurposed antibiotics(e.g.,linezolid),re-engineered oxazolidinones(e.g.,sutezolid),and improved bedaquiline analogues addressing resistance and toxicity.Future strategies emphasize shorter,accessible regimens,reliable drug susceptibility testing(DST),and effective management of treatment failures.Targeted next-generation sequencing(tNGS)has improved resistance detection but remains limited for some second-line drugs.Phenotypic DST is still indispensable.Clinicians must address emerging drug resistance and develop salvage regimens while reducing disease transmission through public health measures.These approaches are critical to improving RR/MDR-TB outcomes globally.展开更多
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...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.展开更多
Background:Multidrug-resistant tuberculosis(MDR-TB)is on the rise in China.This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative ...Background:Multidrug-resistant tuberculosis(MDR-TB)is on the rise in China.This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative control measures.Methods:Eight states of tuberculosis transmission were set up in the Markov model using a hypothetical cohort of 100000 people.The prevalence of MDR-TB and bacteriologically confirmed drug-susceptible tuberculosis(DS-TB+)were simulated and MDR-TB was stratified into whether the disease was treated with the recommended regimen or not.Results:Without any intervention changes to current conditions,the prevalence of DS-TB+was projected to decline 67.7%by 2050,decreasing to 20 per 100000 people,whereas that of MDR-TB was expected to triple to 58/100000.Furthermore,86.2%of the MDR-TB cases would be left untreated by the year of 2050.In the case where MDR-TB detection rate reaches 50%or 70%at 5%per year,the decline in prevalence of MDR-TB would be 25.9 and 36.2%respectively.In the case where treatment coverage was improved to 70%or 100%at 5%per year,MDR-TB prevalence in 2050 would decrease by 13.8 and 24.1%,respectively.If both detection rate and treatment coverage reach 70%,the prevalence of MDR-TB by 2050 would be reduced to 28/100000 by a 51.7%reduction.Conclusions:MDR-TB,especially untreated MDR-TB,would rise rapidly under China’s current MDR-TB control strategies.Interventions designed to promote effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics.展开更多
Background:Antituberculosis-drug resistance is an important public health issue,and its epidemiological patterns has dramatically changed in recent decades.This study aimed to estimate the trends of multidrug-resistan...Background:Antituberculosis-drug resistance is an important public health issue,and its epidemiological patterns has dramatically changed in recent decades.This study aimed to estimate the trends of multidrug-resistant tuberculosis(MDR-TB),which can be used to inform health strategies.Methods:Data were collected from the Global Burden of Disease study 2017.The estimated annual percentage changes(EAPCs)were calculated to assess the trends of MDR-TB burden at global,regional,and national level from 1990 to 2017 using the linear regression model.展开更多
Background:Despite significant advancements in the treatment and diagnosis of tuberculosis(TB)over the past decade,drug-resistant TB remains an increasing threat to public health.TB outbreaks are most commonly reporte...Background:Despite significant advancements in the treatment and diagnosis of tuberculosis(TB)over the past decade,drug-resistant TB remains an increasing threat to public health.TB outbreaks are most commonly reported in schools considering the delay in TB diagnosis,sustained contact,and overcrowding observed in schools.This report describes multidrug-resistant TB(MDR-TB)transmission in a school in Zhejiang Province.We aimed to raise awareness regarding MDR-TB transmission among students.Case presentation:The index patient was a 16-year-old girl in the second year of junior middle school in Zhejiang Province,China,who had been experiencing persistent cough and expectoration for 37 days since 1 March 2014.She tested positive for smear pulmonary and extrapulmonary TB on 8 April 2014 and was subsequently diagnosed with MDR-TB on 1 May 2014.However,the patient was resistant to isoniazid,rifampicin,ethambutol,and streptomycin.Thus,she was suspended from school for anti-TB treatment.All 54 students who were in close contact with the index patient in the same class were screened,and 5 tested positive on the tuberculin skin test.Their exposure time to the index patient was approximately 37 days.Three classmates were subsequently diagnosed with MDR-TB,with similar resistance profiles nearly two years later.Their average discovery delay was 55 days.These three classmates were also suspended from school for anti-TB treatment.During the treatment period,four students visited the local TB-designated hospital for further consultation every month and were followed up once a month by the local community health service center until they were completely cured.Conclusions:Discovery delay for an index patient played a primary role in MDR-TB transmission inside the school.To immediately detect TB,morning examinations in schools should be performed.TB trackers and case managers should work closely with public health workers and physicians in cases of TB outbreaks or transmissions involving students.Moreover,individuals who are in close contact with MDR-TB patients should undergo careful clinical follow-up for at least two years.Implementing a joint examination strategy to ensure early detection,diagnosis,and treatment of MDR-TB transmission is recommended.展开更多
基金supported by the Beijing Municipal Science&Technology Commission(Z191100006619077).
文摘Objectives The combined use of bedaquiline and delamanid(BDQ-DLM)is limited by an increased risk of prolonging the QTc interval.We retrospectively evaluated patients who received DLM/BDQcontaining regimens at a TB-specialized hospital.We aimed to present clinical efficacy and safety data for Chinese patients.Methods This case-control study included patients with multidrug-resistant tuberculosis(MDR-TB)treated with BDQ alone or BDQ plus DLM.Results A total of 96 patients were included in this analysis:64 in the BDQ group and 32 in the BDQ+DLM group.Among the 96 patients with positive sputum culture at the initiation of BDQ alone or BDQ combined with DLM,46 patients(71.9%)in the BDQ group and 29(90.6%)in the BDQ-DLM group achieved sputum culture conversion during treatment.The rate of sputum culture conversion did not differ between the two groups.The time to sputum culture conversion was significantly shorter in the BDQ-DLM group than in the BDQ group.The most frequent adverse event was QTc interval prolongation;however,the frequency of adverse events did not differ between the groups.Conclusion In conclusion,our results demonstrate that the combined use of BDQ and DLM is efficacious and tolerable in Chinese patients infected with MDR-TB.Patients in the BDQ-DLM group achieved sputum culture conversion sooner than those in the BDQ group.
文摘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.
基金supported by The National 13th Five-year Mega-Scientific Projects of Infectious Diseases in China[Grant Number:2017ZX10201302001004]。
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘We followed 188 euthyroidic persons undergoing treatment for multidrug resistant tuberculosis (MDR-TB) in the state of Karnataka, India to determine the incidence of hypothyroidism during anti-tuberculosis treatment. Overall, among MDR-TB patients with valid thyroid stimulating hormone (TSH) values, about 23% developed hypothyroidism (TSH value ≥10 mIU/ml) during anti-tuberculosis treatment;the majority (74%) occurring after 3 months of treatment. Among 133 patients who received a regimen that contained ethionamide, 42 (32%) developed hypothyroidism. Among 17 patients that received a regimen that contained para-aminosalicylate sodium, 6 (35%) developed hypothyroidism. Among 9 HIV positive patients on antiretroviral treatment, 4 (44%) developed hypothyroidism. These results differ from previously reported 4% incidence of hypothyroidism amongst patients who passively reported thyroidal symptoms during treatment, suggesting routine serologic monitoring of TSH throughout the course of treatment for MDR-TB is warranted.
文摘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.
文摘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.
文摘Introduction: The emergency of Mycobacterium tuberculosis resistant to the first line drug reduced access possibility to second line drugs for appropriate treatment and required for urgent action especially in le Democratic Republic of Congo (DRC), which counts among the highest tuberculosis (TB) burden countries in Africa. Objective: To present prevalence and describe multidrug-resistant tuberculosis cases in North-Kivu Province identified by using Genexpert technology. Methods: We conducted an observational prospective study on multidrug-resistant tuberculosis (MDR-TB) cases in North-Kivu Province, DRC from 2017 to 2018. All cases of MDR-TB identified by Genexpert MTB/ RIB were included in this series. Result: Of 15,544 tuberculosis cases registered during the study period, 19 cases of MDR-TB were identified. 57.9% was male, 89.5% was retreatment cases and 5.3% was coinfection HIV/TB cases. Conclusion: This new molecular technology diagnostic facilitates multidrug-resistance tuberculosis detection and improves the reporting of data lack.
文摘Several related substances were detected at trace level in (2R)-2,3-dihydro-2-methyl-6-nitro-2-[[4-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl] phenoxy] methyl]imidazo[2, 1-b]oxazole drug substance by a newly developed high-performance liquid chromatography method. All related substances were characterized rapidly but some impurities were found to be intermediates. Proposed structures were further confirmed by characterization using NMR, FT-IR, and HRMS techniques. Based on the spectroscopic data;unknown related sub-stances were characterized as 1-(Methylsulfonyl)-4-[4-(trifluoromethoxy) phenoxy]piperidine;4-{4-[4-(Tri-fluoromethoxy)-phenoxy]piperidin-1-yl}phenol and 4-{4-[4-(trifluoromethoxy)phenoxy]piperidin-1-yl}phenyl methane sulfonate;4-Bromophenyl methane sulfonate, Ethyl 3,6-dihydro-1(2H)-pyridine carboxylate, (2S)-3-(4-Bromophenoxy)-2-hydroxy-2-methylpropyl methane sulfonate, (2S)-3-(4-Bromophenoxy)-2-methylpropane-1,2-diyldimethane-sulfonate, (2S)-2-Methyl-3-(4-{4-[4-(trifluoromethoxy) phenoxy]-piperidin-1-yl} phenoxy)-propane-1,2-diyldimethane sulfonate, (S)-3-(4-Bromophenoxy)-2-methyl-propane-1,2-diol and corresponding Enantiomer, (2R)-2-[(4-Bromo-phenoxy)methyl]-2-methyloxirane and (2R)-2-[(4-bromophenoxy)methyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b][1,3]oxazole. A possible mechanism for the formation of these related substances is also proposed.
基金supported by the Researchers Supporting Project(project number RSP2024R378),King Saud University,Riyadh,Saudi Arabia.
文摘This study examined the clinical,sociodemographic and treatment-related parameters influencing the therapeutic response to multidrug-resistant(MDR)tuberculosis(TB)treatment in pediatric patients.This multicenter retrospective cross-sectional study was conducted in the programmatic management of drug-resistant tuberculosis sites in Khyber Pakhtunkhwa,Pakistan.Basic character-istics,treatment regimens and outcomes were collected from the TB registries.Out of the 450 patients analyzed,79.1%had successful treatment results,achieving the WHO aim of>75%.Similar to previous studies,this study reported a 5.3%death rate and a 5.6%loss to follow-up.Multivariate analysis showed that no history of prior TB treatment was significantly associated with unfavorable outcomes(ad-justed OR:3.1,95%CI:1.9–5.1,P<0.001).Patients on a specific second-line longer treatment regimen(Lfx,Bdq,Cs,Lzd,Cfz,B6)had higher odds of unsuccessful outcomes(adjusted OR:2.0,P=0.009).Furthermore,patients on shorter treatment regimens were substantially more likely to experience unsuccessful outcomes.The study emphasizes the difficulty in treating children with MDR-TB and the importance of creating individualized treatment programs that take each patient’s medical history and resistance profile into ac-count.Although shorter regimens and newer medications seem promising,further research is required to verify their efficacy.
基金supported by the Global Alliance for TB Drug Development(TB Alliance)the Global Fund(No.:HK.05.01/1/34.3/2018)the World Health Organization(WHO).
文摘Objective:To analyze the risk factors associated with multidrug-resistant tuberculosis(MDR-TB)as a first national survey in Indonesia.Methods:This national coverage cross-sectional study was conducted from 2017 to 2018.The study subjects were selected using a multi-stage probability random sampling method.MDR-TB is tuberculosis caused by bacteria resistant to at least isoniazid and rifampicin.The dependent variable was MDR-TB.Independent variables included age,sex,education,employment status,place of residence,history of living with TB patients,and the number of household members.Univariate and multivariate logistic regression models were used to analyze the risk factors associated with MDR-TB.All the data were analyzed using STATA V.14.0(Stata Corp LLC,College Station,TX).Results:This study found the MDR rate was 109/3234(3.4%)among positive pulmonary TB patients.More than twice as many patients had MDR re-treatment(74/3234,2.3%),compared to 35/3234(1.1%)who had new TB diagnoses or were getting initial treatment.After adjusting for employment status,individuals with a prior history of tuberculosis treatment were found to have significantly higher odds of developing MDR-TB,with an odds ratio of 7.22(95%CI 3.87-13.44).Conclusions:Increasing attention should be paid to these patients to prevent MDR-TB,and MDR-TB transmission is an urgent challenge for controlling TB worldwide.Early detection of MDR-TB is a critical part of TB control programs.
文摘Objective:To evaluate and compare the quality of life(QoL)in patients with multidrug-resistant(MDR-TB)and drug-sensitive(DS-TB)as well as to investigate factors associated with QoL among MDR-TB patients in real-world scenarios at the Haji Hospital,Surabaya.Methods:We conducted a case-control study from June to December 2024.MDR-TB and DS-TB patients were classified into case and control groups,respectively.We used the World Health Organization’s Quality of Life Brief(WHOQOL-BREF)instrument and Patient Health Questionnaire-9(PHQ-9)to assess QoL and depression levels,respectively.Multivariate analysis was used to analyze factors associated with QoL of patients with MDR-TB.Results:Forty-one patients with MDR-TB and 43 with DS-TB were enrolled in the study.A mean score for all domains(physical,psychological,social relationship,environmental)and total mean score of WHOQOL-BREF was significantly lower in MDR-TB than those with DS-TB(P<0.05).The prevalence of depression and the mean score of PHQ-9 were significantly higher in MDR-TB than in DS-TB(P<0.05).PHQ-9 negatively correlates with the WHOQOL-BREF score(r=-0.502,P<0.05)among MDR-TB patients.MDR-TB patients with depression were significantly associated with low QoL in the physical(OR 3.611;95%CI 2.393-6.951;P=0.029),psychological(OR 1.672;95%CI 1.179-5.941;P=0.021),social relationship(OR 2.586;95%CI 1.611-2.909;P=0.014),and environmental domains(OR 1.926;95%CI 1.047-2.147;P=0.048).Conclusions:MDR-TB patients had worse QoL than DS-TB.Those with depression were associated with low QoL.Strategies that identify and tackle alterations in the QoL for MDR-TB patients are necessary during TB treatment.
文摘Tuberculosis(TB)remains the leading infectious disease globally,with 1.25 million deaths and 10.8 million new cases in 2023,including 400,000 rifampin-resistant/multidrug-resistant TB(RR/MDR-TB)cases.RR/MDR-TB accounts for 15–20%of TB-related deaths and poses significant economic and treatment challenges due to low cure rates(68%)and high costs.The heterogeneity of Mycobacterium tuberculosis infections complicates therapy,requiring prolonged regimens and multidrug combinations.Advances in treatment include repurposed antibiotics(e.g.,linezolid),re-engineered oxazolidinones(e.g.,sutezolid),and improved bedaquiline analogues addressing resistance and toxicity.Future strategies emphasize shorter,accessible regimens,reliable drug susceptibility testing(DST),and effective management of treatment failures.Targeted next-generation sequencing(tNGS)has improved resistance detection but remains limited for some second-line drugs.Phenotypic DST is still indispensable.Clinicians must address emerging drug resistance and develop salvage regimens while reducing disease transmission through public health measures.These approaches are critical to improving RR/MDR-TB outcomes globally.
基金The authors declare that they did not receive funding for this research from any source.
文摘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.
基金The study was supported by the Swedish Research Council(No.540–2013-8797 to SH)the National Natural Science Foundation of China(No.81361138019 to BX)joint project(VR-NSFC)the National Science and Technology Major Project of China(No.2018ZX10715012–4 to BX).
文摘Background:Multidrug-resistant tuberculosis(MDR-TB)is on the rise in China.This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative control measures.Methods:Eight states of tuberculosis transmission were set up in the Markov model using a hypothetical cohort of 100000 people.The prevalence of MDR-TB and bacteriologically confirmed drug-susceptible tuberculosis(DS-TB+)were simulated and MDR-TB was stratified into whether the disease was treated with the recommended regimen or not.Results:Without any intervention changes to current conditions,the prevalence of DS-TB+was projected to decline 67.7%by 2050,decreasing to 20 per 100000 people,whereas that of MDR-TB was expected to triple to 58/100000.Furthermore,86.2%of the MDR-TB cases would be left untreated by the year of 2050.In the case where MDR-TB detection rate reaches 50%or 70%at 5%per year,the decline in prevalence of MDR-TB would be 25.9 and 36.2%respectively.In the case where treatment coverage was improved to 70%or 100%at 5%per year,MDR-TB prevalence in 2050 would decrease by 13.8 and 24.1%,respectively.If both detection rate and treatment coverage reach 70%,the prevalence of MDR-TB by 2050 would be reduced to 28/100000 by a 51.7%reduction.Conclusions:MDR-TB,especially untreated MDR-TB,would rise rapidly under China’s current MDR-TB control strategies.Interventions designed to promote effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics.
文摘Background:Antituberculosis-drug resistance is an important public health issue,and its epidemiological patterns has dramatically changed in recent decades.This study aimed to estimate the trends of multidrug-resistant tuberculosis(MDR-TB),which can be used to inform health strategies.Methods:Data were collected from the Global Burden of Disease study 2017.The estimated annual percentage changes(EAPCs)were calculated to assess the trends of MDR-TB burden at global,regional,and national level from 1990 to 2017 using the linear regression model.
基金This study was supported by the quality of life and its influencing factors of MDR-TB patient research(scientific research fund of Zhejiang Provincial Department of Health[2015KYA056]).
文摘Background:Despite significant advancements in the treatment and diagnosis of tuberculosis(TB)over the past decade,drug-resistant TB remains an increasing threat to public health.TB outbreaks are most commonly reported in schools considering the delay in TB diagnosis,sustained contact,and overcrowding observed in schools.This report describes multidrug-resistant TB(MDR-TB)transmission in a school in Zhejiang Province.We aimed to raise awareness regarding MDR-TB transmission among students.Case presentation:The index patient was a 16-year-old girl in the second year of junior middle school in Zhejiang Province,China,who had been experiencing persistent cough and expectoration for 37 days since 1 March 2014.She tested positive for smear pulmonary and extrapulmonary TB on 8 April 2014 and was subsequently diagnosed with MDR-TB on 1 May 2014.However,the patient was resistant to isoniazid,rifampicin,ethambutol,and streptomycin.Thus,she was suspended from school for anti-TB treatment.All 54 students who were in close contact with the index patient in the same class were screened,and 5 tested positive on the tuberculin skin test.Their exposure time to the index patient was approximately 37 days.Three classmates were subsequently diagnosed with MDR-TB,with similar resistance profiles nearly two years later.Their average discovery delay was 55 days.These three classmates were also suspended from school for anti-TB treatment.During the treatment period,four students visited the local TB-designated hospital for further consultation every month and were followed up once a month by the local community health service center until they were completely cured.Conclusions:Discovery delay for an index patient played a primary role in MDR-TB transmission inside the school.To immediately detect TB,morning examinations in schools should be performed.TB trackers and case managers should work closely with public health workers and physicians in cases of TB outbreaks or transmissions involving students.Moreover,individuals who are in close contact with MDR-TB patients should undergo careful clinical follow-up for at least two years.Implementing a joint examination strategy to ensure early detection,diagnosis,and treatment of MDR-TB transmission is recommended.