Second-line anti-TB Treatment Research Articles

Effects of second-line anti-tuberculosis drugs on the intestinal microbiota of patients with rifampicin-resistant tuberculosis.

To determine the effects of second-line anti-tuberculosis (TB) drugs on the composition and functions of intestinal microbiota in patients with rifampicin-resistant TB (RR-TB). In this cross-sectional study, stool samples and relevant clinical information were collected from patients with RR-TB admitted to the Drug-resistant Specialty Department at Hunan Chest Hospital (Hunan Institute For Tuberculosis Control). The composition and functions of intestinal microbiota were analyzed using metagenomic sequencing and bioinformatics methods. Altered structural composition of the intestinal microbiota was found when patients from the control, intensive phase treatment, and continuation phase treatment groups were compared (P<0.05). Second-line anti-TB treatment resulted in a decrease in the relative abundance of species, such as Prevotella copri, compared with control treatment. However, the relative abundance of Escherichia coli, Salmonella enterica, and 11 other conditionally pathogenic species increased significantly in the intensive phase treatment group. Based on differential functional analysis, some metabolism-related functions, such as the biosynthesises of phenylalanine, tyrosine, and tryptophan, were significantly inhibited during second-line anti-TB drug treatment, while other functions, such as phenylalanine metabolism, were significantly promoted during the intensive phase of treatment. Second-line anti-TB drug treatment caused changes in the structural composition of the intestinal microbiota in patients with RR-TB. In particular, this treatment induced a significant increase in the relative abundance of 11 conditionally pathogenic species, including Escherichia coli. Functional analysis revealed significantly decreased biosynthesises of phenylalanine, tyrosine, and tryptophan and significantly increased phenylalanine metabolism.

Alcohol drinking delays the rate of sputum smear conversion among DR-TB patients in northwest Ethiopia; A retrospective follow-up study.

Sputum smear microscopy is simple and feasible technique to assess the presence of acid-fast bacilli (AFB) in the respiratory tract of patients with Drug Resistance Tuberculosis (DR-TB). Conversion of sputum smear from positive to negative is considered as an interim indicator of efficacy of anti-tubercular treatment and the program effectiveness. Although evidences regarding the factors affecting the sputum smear conversion are available on drug susceptible TB patients, there is dearth of literature about smear conversion and its predictors among DR-TB patients in the study setting. Hence, shortening the time to sputum smear conversion is desirable to reduce the likelihood of mycobacterial transmission. This study has therefore aimed at estimating the median time of sputum smear conversion and to determine its predictors. This was a retrospective follow-up study conducted among DR-TB patients registered for second-line anti-TB treatment in the four hospitals of Amhara regional state, Northwest Ethiopia. Of all patients enrolled to DR-TB treatment in the study setting from 2010 to 2017, 436 patients have been include for this study who fulfilled the eligibility criteria. The cox proportional hazard model was fitted and the adjusted hazard ratio (AHR) with 95% confidence interval (CI) and p <0.05 was used to declare statistical significance of the variables associated with the smear conversion. From the 436 patients with sputum smear positive at baseline, 351 (80.5%) converted sputum smear at a median time of 48 (IQR: 30-78) days. The median time of smear conversion was 59 (95% CI: 42, 74) and 44 (95% CI: 37, 54) days among patients who had and had no history of alcohol drinking, respectively. Similarly, the median time to smear conversion was 61 (95% CI: 36, 73) days among patients with comorbid conditions and 44 (95% CI: 38, 54) days among patients with no comorbid conditions. In the multi-variable analysis, only history of alcohol consumption [AHR = 0.66 (0.50, 0.87)] was found to delay significantly the rate of sputum smear conversion. In our study, the median time of sputum smear conversion was with in the expected time frame of conversion. History of alcohol consumption was found to delay significantly the rate of sputum smear conversion. The DR-TB patients are strongly advised to avoid alcohol consumption.

Predictors of mortality in patients with drug-resistant tuberculosis: A systematic review and meta-analysis.

Even though the lives of millions have been saved in the past decades, the mortality rate in patients with drug-resistant tuberculosis is still high. Different factors are associated with this mortality. However, there is no comprehensive global report addressing these risk factors. This study aimed to determine the predictors of mortality using data generated at the global level. We systematically searched five electronic major databases (PubMed/Medline, CINAHL, EMBASE, Scopus, Web of Science), and other sources (Google Scholar, Google). We used the Joanna Briggs Institute Critical Appraisal tools to assess the quality of included articles. Heterogeneity assessment was conducted using the forest plot and I2 heterogeneity test. Data were analyzed using STATA Version 15. The pooled hazard ratio, risk ratio, and odd's ratio were estimated along with their 95% CIs. After reviewing 640 articles, 49 studies met the inclusion criteria and were included in the final analysis. The predictors of mortality were; being male (HR = 1.25,95%CI;1.08,1.41,I2;30.5%), older age (HR = 2.13, 95%CI;1.64,2.62,I2;59.0%,RR = 1.40,95%CI; 1.26, 1.53, I2; 48.4%) including a 1 year increase in age (HR = 1.01, 95%CI;1.00,1.03,I2;73.0%), undernutrition (HR = 1.62,95%CI;1.28,1.97,I2;87.2%, RR = 3.13, 95% CI; 2.17,4.09, I2;0.0%), presence of any type of co-morbidity (HR = 1.92,95%CI;1.50-2.33,I2;61.4%, RR = 1.61, 95%CI;1.29, 1.93,I2;0.0%), having diabetes (HR = 1.74, 95%CI; 1.24,2.24, I2;37.3%, RR = 1.60, 95%CI;1.13,2.07, I2;0.0%), HIV co-infection (HR = 2.15, 95%CI;1.69,2.61, I2; 48.2%, RR = 1.49, 95%CI;1.27,1.72, I2;19.5%), TB history (HR = 1.30,95%CI;1.06,1.54, I2;64.6%), previous second-line anti-TB treatment (HR = 2.52, 95% CI;2.15,2.88, I2;0.0%), being smear positive at the baseline (HR = 1.45, 95%CI;1.14,1.76, I2;49.2%, RR = 1.58,95%CI;1.46,1.69, I2;48.7%), having XDR-TB (HR = 2.01, 95%CI;1.50,2.52, I2;60.8%, RR = 2.44, 95%CI;2.16,2.73,I2;46.1%), and any type of clinical complication (HR = 2.98, 95%CI; 2.32, 3.64, I2; 69.9%). There are differences and overlaps of predictors of mortality across different drug-resistance categories. The common predictors of mortality among different drug-resistance categories include; older age, presence of any type of co-morbidity, and undernutrition. Different patient-related demographic (male sex, older age), and clinical factors (undernutrition, HIV co-infection, co-morbidity, diabetes, clinical complications, TB history, previous second-line anti-TB treatment, smear-positive TB, and XDR-TB) were the predictors of mortality in patients with drug-resistant tuberculosis. The findings would be an important input to the global community to take important measures.

Deficiency in Fat-soluble Vitamins A, D, E in Patients with Pulmonary Multidrug-Resistant Tuberculosis

Objective: The treatment management of Multidrug-Resistant Tuberculosis (MDR-TB) is a major global public health problem. The development of this form of tuberculosis increases immune deficiency and the production of free radicals in the body. Micronutrients, especially fat-soluble vitamins A, D, and E, play an essential role in the immune system by protecting and renewing cells. The objective of this study is to determine the profiles of vitamins A, D, and E in order to evaluate the performance of the immune defenses of MDR-TB under second-line anti-TB treatment. Methods: The analysis of vitamins A, D and E was carried out using an HPLC chain, in isocratic mode by UV-Visible detection after prior extraction of the lipid fraction from the serum in the hexane protected away from light. Results: MDR-TB showed a significant decrease in the concentration of vitamins A, D, and E (p˂0.05) with high reduction levels of 80%, 40% and 50%, respectively. Conclusion: The persistence of this deficit after six months of TB treatment highlights the need for corrective measures to be taken, such as the supplementation of vitamins A, D, and E. J Microbiol Infect Dis 2020; 10(4): 199-207.

Poor outcomes in a cohort of HIV-infected adolescents undergoing treatment for multidrug-resistant tuberculosis in Mumbai, India.

BackgroundLittle is known about the treatment of multidrug-resistant tuberculosis (MDR-TB) in HIV-co-infected adolescents. This study aimed to present the intermediate outcomes of HIV-infected adolescents aged 10–19 years receiving second-line anti-TB treatment in a Médecins Sans Frontières (MSF) project in Mumbai, India.MethodsA retrospective review of medical records of 11 adolescents enrolled between July 2007 and January 2013 was undertaken. Patients were initiated on either empirical or individualized second-line ambulatory anti-TB treatment under direct observation.ResultsThe median age was 16 (IQR 14–18) years and 54% were female. Five (46%) adolescents had pulmonary TB (PTB), two (18%) extrapulmonary disease (EPTB) and four (36%) had both. Median CD4 count at the time of MDR-TB diagnosis was 162.7 cells/µl (IQR: 84.8–250.5). By January 2013, eight patients had final and 3 had interim outcomes. Favourable results were seen in four (36.5%) patients: one was cured and three were still on treatment with negative culture results. Seven patients (64%) had poor outcomes: four (36.5%) died and three (27%) defaulted. Three of the patients who died never started on antiretroviral and/or TB treatment and one died 16 days after treatment initiation. Two of the defaulted died soon after default. All patients (100%) on-treatment experienced adverse events (AEs): two required permanent discontinuation of the culprit drug and two were hospitalized due to AEs. No patient required permanent discontinuation of the entire second-line TB or antiretroviral regimens.ConclusionsEarly mortality and mortality after default were the most common reasons for poor outcomes in this study. Early mortality suggests the need for rapid diagnosis and prompt treatment initiation, and adolescents might benefit from active contact-tracing and immediate referral. Default occurred at different times, suggesting the need for continuous, intensified and individualized psychosocial support for co-infected adolescents. Operational research among co-infected adolescents will be especially important in designing effective interventions for this vulnerable group.

MDR TB Transmission, Singapore

MDR TB Transmission, Singapore

Adverse Events among HIV/MDR-TB Co-Infected Patients Receiving Antiretroviral and Second Line Anti-TB Treatment in Mumbai, India

BackgroundSignificant adverse events (AE) have been reported in patients receiving medications for multidrug- and extensively-drug-resistant tuberculosis (MDR-TB & XDR-TB). However, there is little prospective data on AE in MDR- or XDR-TB/HIV co-infected patients on antituberculosis and antiretroviral therapy (ART) in programmatic settings.MethodsMédecins Sans Frontières (MSF) is supporting a community-based treatment program for drug-resistant tuberculosis in HIV-infected patients in a slum setting in Mumbai, India since 2007. Patients are being treated for both diseases and the management of AE is done on an outpatient basis whenever possible. Prospective data were analysed to determine the occurrence and nature of AE.ResultsBetween May 2007 and September 2011, 67 HIV/MDR-TB co-infected patients were being treated with anti-TB treatment and ART; 43.3% were female, median age was 35.5 years (Interquartile Range: 30.5–42) and the median duration of anti-TB treatment was 10 months (range 0.5–30). Overall, AE were common in this cohort: 71%, 63% and 40% of patients experienced one or more mild, moderate or severe AE, respectively. However, they were rarely life-threatening or debilitating. AE occurring most frequently included gastrointestinal symptoms (45% of patients), peripheral neuropathy (38%), hypothyroidism (32%), psychiatric symptoms (29%) and hypokalaemia (23%). Eleven patients were hospitalized for AE and one or more suspect drugs had to be permanently discontinued in 27 (40%). No AE led to indefinite suspension of an entire MDR-TB or ART regimen.ConclusionsAE occurred frequently in this Mumbai HIV/MDR-TB cohort but not more frequently than in non-HIV patients on similar anti-TB treatment. Most AE can be successfully managed on an outpatient basis through a community-based treatment program, even in a resource-limited setting. Concerns about severe AE in the management of co-infected patients are justified, however, they should not cause delays in the urgently needed rapid scale-up of antiretroviral therapy and second-line anti-TB treatment.

Standardized Second-line Anti-TB Treatment of Multidrug-Resistant Tuberculosis During Pregnancy: Maternal and Neonatal Safety and Outcome

PURPOSE: To study the efficacy, safety, and outcome of standardized second-line anti-TB treatment of multidrug-resistant tuberculosis (MDR-TB) during pregnancy focusing on maternal and perinatal outcomes. METHODS: Prospective study conducted to evaluate the outcomes of standardized MDR-TB treatment during pregnancy in patients referred to NRITLD from 2003 to 2008. Outcomes are investigated in two categories, namely, maternal and neonatal. RESULTS: Five MDR-TB patients whilst receiving standardized anti-TB regimen became pregnant. We did not change the regimen and all of them did not reveal any adverse effects throughout pregnancy and delivery. No adverse effect occurred for the mothers and the neonates, either. CONCLUSION: Treatment of MDR-TB in pregnancy with standardized second-line regimen could be safe and the rate of successful outcome is acceptable. CLINICAL IMPLICATIONS: Although recommendations for the treatment of pregnant women with pulmonary TB are available, there is no unique guideline for treatment of MDR-TB during pregnancy. The response to treatment is not clear and it has not been yet elucidated which drugs are safe during pregnancy in these patients. In this study all patients received the same standardized regimen of medications. Accordingly, evaluation of patients’ response to treatment and side effects of the treatment could be readily evaluated and compared in a uniform format. DISCLOSURE: Ahmadreza Moradi, No Financial Disclosure Information; No Product/Research Disclosure Information 12:45 PM 2:00 PM Copyright © 2014 American College of Chest Physicians Standardized Second-line Anti-TB Treatment of Multidrug-Resistant Tuberculosis During Pregnancy: Maternal and Neonatal Safety and Outcome Chest. 2010;138(4_MeetingAbstracts):678A. doi:10.1378/chest.9319 FREE TO VIEW Page 1 of 1 7/13/2014 http://journal.publications.chestnet.org/article.aspx?articleid=1086711&resultClick=1

Management of Extensively Drug-Resistant Tuberculosis in Peru: Cure Is Possible

AimTo describe the incidence of extensive drug-resistant tuberculosis (XDR-TB) reported in the Peruvian National multidrug-resistant tuberculosis (MDR-TB) registry over a period of more than ten years and present the treatment outcomes for a cohort of these patients.MethodsFrom the Peruvian MDR-TB registry we extracted all entries that were approved for second-line anti-TB treatment between January 1997 and June of 2007 and that had Drug Susceptibility Test (DST) results indicating resistance to both rifampicin and isoniazid (i.e. MDR-TB) in addition to results for at least one fluoroquinolone and one second-line injectable (amikacin, capreomycin and kanamycin).ResultsOf 1,989 confirmed MDR-TB cases with second-line DSTs, 119(6.0%) XDR-TB cases were detected between January 1997 and June of 2007. Lima and its metropolitan area account for 91% of cases, a distribution statistically similar to that of MDR-TB. A total of 43 XDR-TB cases were included in the cohort analysis, 37 of them received ITR. Of these, 17(46%) were cured, 8(22%) died and 11(30%) either failed or defaulted treatment. Of the 14 XDR-TB patients diagnosed as such before ITR treatment initiation, 10 (71%) were cured and the median conversion time was 2 months.ConclusionIn the Peruvian context, with long experience in treating MDR-TB and low HIV burden, although the overall cure rate was poor, a large proportion of XDR-TB patients can be cured if DST to second-line drugs is performed early and treatment is delivered according to the WHO Guidelines.