Resistant Tuberculosis Research Articles

Differences in pulmonary nodular consolidation and pulmonary cavity among drug-sensitive, rifampicin-resistant and multi-drug resistant tuberculosis patients: the Guangzhou computerized tomography study.

Pulmonary nodular consolidation (PN) and pulmonary cavity (PC) may represent the two most promising imaging signs in differentiating multidrug-resistant (MDR)-pulmonary tuberculosis (PTB) from drug-sensitive (DS)-PTB. However, there have been concerns that literature described radiological feature differences between DS-PTB and MDR-PTB were confounded by that MDR-PTB cases tend to have a longer history. This study seeks to further clarify this point. All cases were from the Guangzhou Chest Hospital, Guangzhou, China. We retrieved data of consecutive new MDR cases [n=46, inclusive of rifampicin-resistant (RR) cases] treated during the period of July 2020 and December 2021, and according to the electronic case archiving system records, the main PTB-related symptoms/signs history was ≤3 months till the first computed tomography (CT) scan in Guangzhou Chest Hospital was taken. To pair the MDR-PTB cases with assumed equal disease history length, we additionally retrieved data of 46 cases of DS-PTB patients. Twenty-two of the DS patients and 30 of the MDR patients were from rural communities. The first CT in Guangzhou Chest Hospital was analysed in this study. When the CT was taken, most cases had anti-TB drug treatment for less than 2 weeks, and none had been treated for more than 3 weeks. Apparent CT signs associated with chronicity were noted in 10 cases in the DS group (10/46) and 9 cases in the MDR group (10/46). Thus, the overall disease history would have been longer than the assumed <3 months. Still, the history length difference between DS patients and MDR patients in the current study might not be substantial. The lung volume involvement was 11.3%±8.3% for DS cases and 8.4%±6.6% for MDR cases (P=0.022). There was no statistical difference between DS cases and MDR cases both in PN prevalence and in PC prevalence. For positive cases, MDR cases had more PN number (mean of positive cases: 2.63 vs. 2.28, P=0.38) and PC number (mean of positive cases: 2.14 vs. 1.38, P=0.001) than DS cases. Receiver operating characteristic curve analysis shows, PN ≥4 and PC ≥3 had a specificity of 86% (sensitivity 25%) and 93% (sensitivity 36%), respectively, in suggesting the patient being a MDR cases. A combination of PN and PC features allows statistical separation of DS and MDR cases.

Determinants of sputum culture conversion time in multidrug-resistant tuberculosis patients in ALERT comprehensive specialized hospital, Addis Ababa, Ethiopia: A retrospective cohort study.

The treatment response of multi-drug resistance tuberculosis (MDR-Tuberculosis) patients is mainly dictated by the sputum culture conversion. An earlier culture conversion is a remarkable indicator of the improvement in the treatment response. In this study, we aimed to determine the time to culture conversion and its associated factors among MDR-Tuberculosis patients in All Africa Leprosy, Tuberculosis and Rehabilitation Training Center (ALERT) Hospital, Addis Ababa, Ethiopia. A retrospective cohort study was conducted on 120 MDR-Tuberculosis patients attending ALERT Hospital from 2018-2022. Kaplan-Meier methods were used to determine the time to initial sputum culture conversion. All relevant laboratory, socio-demographic characteristics, and other clinical data were collected by chart abstraction using a structure data extraction form. The log-rank test was used to determine the survival rate. To identify the predictors of culture conversion, bivariate and multivariate Cox proportional hazard regression analysis was used. The hazard ratio (HR) with a 95% confidence interval was used to estimate the effect of each variable on the initial culture conversion. A test with a P value of < 0.05 was considered statistically significant. From the total of 120 study participants, 89.2% (107/120) have shown a successful culture conversion. The median age of the participants was 30 years (IQR = 12). The study participants were followed for 408.6 person-months (34.05 person-years). The median time to initial sputum culture conversion was 80 days. The median time to initial sputum culture conversion among HIV-positive and HIV-negative participants was 61 days (IQR = 58-63.5) and 88 days (IQR = 75-91), respectively. HIV-negative and patients with previous treatment history were shown to be the predictor for a prolonged time to initial sputum culture conversion, (aHR = 0.24 (95% CI: 0.1-0.4), P value <0.001) and (aHR = 0.47 (95% CI: 0.31-0.71), P value <0.001) respectively. The median time to sputum culture conversion for HIV positive was found to be 61 days in our study. Notably, patients with a history of previous anti-tuberculosis treatment, HIV-negative status, and higher bacillary load at baseline exhibited delayed culture conversion. These findings underscore the importance of considering such patient characteristics in the management of MDR-TB cases, as tailored interventions and close monitoring may lead to more favorable treatment outcomes. By identifying individuals with these risk factors early in the treatment process, healthcare providers can implement targeted strategies to optimize patient care and improve overall treatment success rates in MDR-TB management programs.

Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

Assessment of the Indirect Cost of Drug Resistant Tuberculosis Treatment to Patients in a High Burden, Low Income Setting in Mozambique

Profile of gene mutations responsible for M.Tuberculosis resistance to antituberculosis drugs

The implementation of rapid diagnostic tests and drug susceptibility testing requires a complex approach to these methods. The pattern of gene mutations responsible for resistance to first-line antituberculosis drugs was studied in patients with resistant tuberculosis undergoing treatment in the inpatient department of the Phthisiopneumology Institute. The obtained results were compared with similar data from previous studies. It was determined that in the last 5 years the resistance to RIF is predominantly determined by the rpoB S531L mutation (82.9%), for the resistance to INH the katG S315T1 mutation (94.6%) is responsible.

Relationship between HIV viral suppression and multidrug resistant tuberculosis treatment outcomes.

The impact of HIV viral suppression on multidrug resistant tuberculosis (MDR-TB) treatment outcomes among people with HIV (PWH) has not been clearly established. Using secondary data from a cluster-randomized clinical trial among people with MDR-TB in South Africa, we examined the effects of HIV viral suppression at MDR-TB treatment initiation and throughout treatment on MDR-TB outcomes among PWH using multinomial regression. This analysis included 1479 PWH. Viral suppression (457, 30.9%), detectable viral load (524, 35.4%), or unknown viral load (498, 33.7%) at MDR-TB treatment initiation were almost evenly distributed. Having a detectable HIV viral load at MDR-TB treatment initiation significantly increased risk of death compared to those virally suppressed (relative risk ratio [RRR] 2.12, 95% CI 1.11-4.07). Among 673 (45.5%) PWH with a known viral load at MDR-TB outcome, 194 (28.8%) maintained suppression, 267 (39.7%) became suppressed, 94 (14.0%) became detectable, and 118 (17.5%) were never suppressed. Those who became detectable (RRR 11.50, 95% CI 1.98-66.65) or were never suppressed (RRR 9.28, 95% CI 1.53-56.61) were at significantly increased risk of death (RRR 6.37, 95% CI 1.58-25.70), treatment failure (RRR 4.54, 95% CI 1.35-15.24), and loss to follow-up (RRR 7.00, 95% CI 2.83-17.31; RRR 2.97, 95% CI 1.02-8.61) compared to those who maintained viral suppression. Lack of viral suppression at MDR-TB treatment initiation and failure to achieve or maintain viral suppression during MDR-TB treatment drives differences in MDR-TB outcomes. Early intervention to support access and adherence to antiretroviral therapy among PWH should be prioritized to improve MDR-TB treatment outcomes.

The potential of several compounds in Peperomia pellucida as a solution to rifampicin resistance in tuberculosis disease

Background: Tuberculosis is a lung disease caused by Mycobacterium tuberculosis. In 2018, the incidence of tuberculosis in Indonesia was 1,017,290. The number of cases was accompanied by an increase in the number of resistances to first-line antibiotics (rifampicin) used due to patient non-compliance as well as the long duration of treatment. The increase in resistance around the world is always increasing every year by about 2%. Therefore, we need another alternative to existing plants in Indonesia that has the potential to be a solution to the problem and overcome resistance to these treatments.Objective: This review was conducted to find out the potential of Peperomia pellucida as an antituberculosis drug that can be a solution to rifampicin resistance in tuberculosis disease. Results: The results of the literature review showed that the Peperomia pellucida or suruhan plants have antibacterial potential against Mycobacterium tuberculosis because it contains a class of alkaloid compounds that function to inhibit deprenyl-phosphoryl-β-D-ribose-2 oxidase (an enzyme responsible for the biosynthesis of arabinogalactan in the cell walls of Mycobacterium tuberculosis), a flavonoid that has activity inhibition of fatty acid synthase II (FAS-II) enzymes, tannins that can precipitate proteins in Mycobacterium tuberculosis, and triterpenoids that have an activation mechanism of intracellular killing cascades in host cells during tuberculosis bacterial infection.Conclusion: Peperomia pellucida or suruhan plants have the potential to be further investigated as a solution to overcome rifampicin resistance in tuberculosis disease.Keywords: Mycobacterium tuberculosis, rifampicin resistance, Peperomia pellucida

Molecular epidemiology and drug resistance of Mycobacterium tuberculosis in a tertiary care hospital in northeastern Mexico.

Tuberculosis (TB) is a re-emerging disease considered a public health concern. In the present study, we analyzed the epidemiology and drug resistance of Mycobacterium tuberculosis strains isolated from patients with pulmonary TB. Mycobacterium tuberculosis isolates (n = 190) were obtained from patients with pulmonary TB admitted to Dr. José Eleuterio González University Hospital (UH). Each M. tuberculosis isolate was analyzed by spoligotyping (spacer oligonucleotide typing) and MIRU-VNTR (Mycobacterial Interspersed Repetitive Units-Variable Number Tandem Repeat). Drug resistance was evaluated using the Anyplex™ II MTB/MDR/XDR assay. The predominant spoligotypes observed were X1 (SIT 119, n = 46), T1 (SIT 53, n = 40), H3 (SIT 50, n = 13), Beijing (SIT 1, n = 11), and EAI2-Manila (SIT 19, n = 8). MIRU-VNTR analysis showed that the locus QUB-26 had the highest allelic variability. The observed drug resistance included monoresistance to rifampicin (2.6%; n = 5), isoniazid (3.2%; n = 6), and fluoroquinolones (1.6%; n = 3) as well as multidrug resistance (5.3%; n = 10). All of the Beijing strains were susceptible. Regarding comorbidities, 13.7% (26/190) of the patients were co-infected with TB and HIV (TB+HIV+), and 31.6% (55/190) had TB along with diabetes (TB + diabetes). The most prevalent lineages were X1 (SIT 119; 24.3%) and T1 (SIT 53; 21%). An alarming proportion (12.6%) of M. tuberculosis isolates presented drug resistance. To effectively manage TB, continuous surveillance of regional strain dissemination, drug resistance profiles, and TB-associated comorbidities is crucial.

Pyrazinamide Resistance among Multi Drug Resistant Tuberculosis Patients in Karnataka: Cross Sectional Study from a Referral Centre

This study aimed to investigate the rate of occurrence of pyrazinamide (PZA) resistance among patients with MDR-TB from the clinical specimens submitted to a referral centre in Bengaluru, Karnataka. PZA has been used for almost 50 years as first line drug for short course chemotherapy against MTB and its inclusion has significantly shortened the treatment duration to 6 months. However, resistance to PZA is associated with poor treatment outcomes and its drug susceptibility testing (DST) is not routinely performed in public health laboratories in India due to technical difficulties. This study followed a structured approach to investigate PZA resistance among MDRTB patients in Karnataka. Relevant demographic and clinical information was collected from Laboratory registers. The specimens yielding the growth of Mycobacterium tuberculosis were subjected to DST for PZA using validated techniques and the rate of PZA resistance was determined. Our results showed 4% of PZA resistance among MDRTB specimens. These results can contribute to the understanding of local epidemiology of drug resistant TB and update public health strategies for TB control in a particular geographical region. The findings may highlight the need for routine DST for PZA in public health laboratories in India and further research to better understand the associated factors with PZA resistance. This study also emphasizes the importance of continued surveillance of drug resistance patterns to guide evidence-based interventions for TB control and management.

Drug-resistant pulmonary tuberculosis at Maradi Regional Hospital Center, Niger (2014-2018)

To describe the clinical, therapeutic and evolutionary profile of patients followed for rifampicin-resistant pulmonary tuberculosis (RR-TB) at the Regional Hospital Centre (RHC) of Maradi (Niger) from 2014 to 2018. We conducted a retrospective and descriptive study based on the records of patients followed for Multidrug-resistant tuberculosis (MDR-TB) between January 1, 2014 and June 30, 2018 at the resistant tuberculosis management unit in Maradi (Niger). This unit is located within the RHC of Maradi and has a capacity of 20 beds in 4 wards. It receives patients with tuberculosis resistant to first-line anti-tuberculosis drugs. In this study, patients diagnosed with RR-TB by genotypic (GeneXpert MTB/RIF) or phenotypic (culture) testing were included. We excluded from this study: patients previously treated for more than 1 month with second-line anti-TB drugs; patients with resistance to second-line injectables (SLI) and/or fluoroquinolones (FQ); patients with an electrocardiogram QTc greater than 500 ms (the corrected QT (QTc) estimates the QT interval at a rate of 60 beats per second); cases of atypical mycobacteriosis detected by phenotypic testing.Patients were previously on 2RHZE/4RH prior to the discovery of resistance. The treatment protocol for resistant TB was as follows: 4KmMfxPtoCfzHZE/5MfxCfzZE (The second-line injectable was replaced by Lzd in case of initial or treatment-emergent deafness). HIV co-infected patients received, in addition to anti-tuberculosis drugs, antiretrovirals and cotrimoxazole in preventive doses. A total of 80 patients were included in the present study (70 males and 10 females, mean age 34.4 years with extremes ranging from 18 to 71 years). Patients aged 18-35 years accounted for more than half. Patients with primary treatment failure were the most frequent type (36%) followed by patients with retreatment failure (24%) and patients with retreatment relapse (17%). It should be noted that 77 patients (96%) were previously treated for TB and only 3 patients (4%) were new cases. The majority of patients (70%) had a Body mass index of less than 18 kg/m2. 7.5% of patients were HIV positive, one was diabetic, 52% of the patients had grade 2 radiological lesions. Grade 1 deafness was noted at the beginning of treatment in 3%. A third of patients (36%) were primary treatment failures. The treatment protocol was as follows: 4KmMfxPtoCfzHZE/5MfxCfzZE. Only 1 patient had a positive culture at the end of the 4th month of treatment. Most of the patients had experienced adverse events, mainly digestive, with vomiting being the most common. The therapeutic success rate was 88%. We noted 10% of deaths, 1% of therapeutic failure and 1% of lost to follow-up.Six months after treatment, 48 patients (60%) were smear negative and 43 (54%) were culture negative. In 32 patients (40%), the smear was not performed and culture was not performed in 37. The short treatment regime gives satisfactory results in the absence of resistance to fluoroquinolones, with rare adverse effects. In Niger, further efforts should be made to minimize the delay in diagnosis which is responsible for most deaths during treatment. A centre could usefully be designated to organize "TB consiliums" allowing any practitioner to submit difficult cases of MDR-TB.

Incidence of Rifampicin-Resistant Strains in Pediatric Cases Newly Identified with Pulmonary Tuberculosis

Background: To assess the effect of rifamycin prevalence which create resistant in newly diagnosed pediatric patients having pulmonary infections. Objectives: This scientific research was conducted to evaluate the prevalence of antibiotics resistivity in pediatric children specifically under age. The primary antibiotics were found to be resistant when given to children at the onset of disease. The investigation was done to evaluate the efficacy of the rifamycin antibiotic as treatment option which will excite the comprehension of drug resistant tuberculosis in pediatric population under the specific age. Study Design: Cross sectional study. Settings: The study was conducted in Children Hospital, Lahore Pakistan. Duration: The study was conducted duration the time period staring from 24 May 2023 to 23 November 2023. Methods: The current study was conducted under the criteria of cross-sectional information to assess the antibiotics resistant in bacterial pathogens among the chronic disease as tuberculosis patient specifically children. The evaluation was purely done on the basis of statistical analysis by using statistical tools to examine the gender base medication relevant factors involved in occurring of disease. the resistivity was identified with particular factors. The evaluation was done on behalf of statistical tools SPSS version 23. Results: The current research offers the valuable insight the prevalence of antibiotics rifamycin resistivity in the children with the disease of lungs like tuberculosis or other lungs issues regarding to bacterial infection. The suitable treatment strategies were made, and drug resistant was confirmed. Conclusion: The study undergoes the prevalence of the drug resistant bacterial infection caused by specifically limitation of drugs effectivity against bacteria. The elevated resistant rate rephasing the necessity to explore the alternativity for the effective prevention and management of drug resistant tuberculosis in pediatric patients.

Catch them young: Knowledge gaps about drug resistant tuberculosis among Homoeopathy college interns: Apre and post-test study

Background: India is the highest Tuberculosis (TB) burden country in the world. It also has the second highest burden of Multidrug-resistant TB globally. Many precious lives are lost due to Drug-resistant TB (DR TB) every day. To achieve the goal of TB elimination in India, robust primary health care is mandatory. Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homeopathy (AYUSH) practitioners provide a quarter of primary health care in India. Since interns working at Homoeopathic Medical college will be the future primary care providers, their awareness about DR TB will help reach the target of End TB by 2025. Objective:The study objective was to assess the knowledge gained by Homoeopathy college interns in the diagnosis and treatment of DR TB following a single-day training session. Materials and methods: This cross-sectional study was carried out among 33 interns of Bharati Vidyapeeth (Deemed to be University) Homoeopathic Medical College, Pune. Aquestionnaire was given in the form of a pre-test before the training session. The training comprised the epidemiology of DR TB, its diagnosis,treatment, counseling, and need for referral. After completion of training, a post-test was given, and scores were calculated. A two-tailed paired sample t-test was used to assess gain in knowledge. The proportion of participants with correct responses for every question was determined and compared before and after training using the McNemar test. P&lt;0.05 was considered statistically significant. Result: The mean pre-test score was 2.30 ± 1.24, while the mean post-test score was 4.24 ± 2.00 (p&lt;0.001). There was less knowledge about the regime for DR TB, pre-treatment evaluation, gene Xpert method, and empirical Anti-tuberculosis Treatment. Conclusion: This study highlights that there are significant gaps in knowledge about DR TB among Homoeopathy college interns. It also showed that a short training session significantly improved their knowledge.

PENERAPAN TRANSTHEORICAL MODEL BEHAVIORAL CHANGE TERHADAP KEPATUHAN BEROBAT PADA PASIEN MULTIDRUG RESISTANT TUBERCULOSIS DI PUSKESMAS KOTA DAN KABUPATEN JAYAPURA

Multi Drug Resistant Tuberculosis (MDR-TB) is still a global health problem. Indonesia is the 3rd country with an average of 5% cases per 100,000 population. For the Papua region, MDR-TB is still a major problem because the treatment success rate has not reached the WHO indicator (68.7%). The treatment of MDR-TB is complex and time-consuming, making patients non-compliant. Reports of low patient visits have made it possible to develop a promotive service program based on applying the Transtheoretical Model (TTM) of Behavioral Change. The TTM Model focuses on changing behavior with the main component of self-efficacy. The study aimed to determine the characteristics of patients, treatment compliance of MDR-TB patients, analyze the effect of applying the TTM behavioral change model with the level of treatment compliance of MDR-TB patients. The research method used a pre-experiment design with a one-group pre-test-post-test design. The study population was 35 patients at the city and district health centers of Jayapura. The instruments used were the Self-Efficacy For Appropriate Medication Use Scale (SEAMS) and TB Medication Adherence Scale (TBMAS). The effect test used a paired sample t-test with significance level p-value=0.05. This indicates an effect of changes in compliance behavior after being given health promotion by applying the Transtheoretical Model. Substantially, the level of adherence to taking medication in MDR-TB patients is also influenced by belief and motivation to recover. There is support from nurses at the puskesmas who often provide behavior change promotions, so patients have the strength and support of a good system that has a positive impact on increasing thoughts to achieve recovery. The importance of Increasing health promotion based on behavior change in MDR-TB patients can increase self-efficacy to recover so that it has an impact on adherence to taking medication.

Изучение эффективности нового противотуберкулезного препарата тиозонид у пациентов с туберкулезом легких с множественной и широкой устойчивостью M. tuberculosis

Изучение эффективности нового противотуберкулезного препарата тиозонид у пациентов с туберкулезом легких с множественной и широкой устойчивостью M. tuberculosis

Using ultrasound guided needle biopsy in conjunction with GeneXpert MTB/RIF to diagnose epididymal tuberculosis

This study aimed to investigate the diagnostic utility of percutaneous ultrasound-guided needle biopsy conjunction with GeneXpert MTB/RIF for epididymal tuberculosis. A retrospective analysis was conducted on the pathological and laboratory examinations of 20 patients with epididymal lesions undergoing ultrasound guided biopsy at Shandong Public Health Clinical Center. Laboratory examination included acid-fast staining, Mycobacterium tuberculosis culture by BACTEC MGIT 960, and GeneXpert MTB/RIF test. Diagnosis and complications were comprehensively analyzed. Among the 20 patients, 15 had epididymal tuberculosis and 5 had non-epididymal tuberculosis. Ten patients had granulomatous inflammation and necrotic tissues. The sensitivity and specificity of acid-fast staining, Mycobacterium tuberculosis culture, and GeneXpert MTB/RIF for the diagnosis of epididymis tuberculosis were 26.67% and 100.00%, 33.33% and 100.00%, and 86.67% and 100.00%, respectively. The diagnostic value analysis of the 3 detection techniques indicated that the GeneXpert MTB/RIF technique (Kappa = 0.765, Area under the curve (AUC) = 0.933) was superior to Mycobacterium tuberculosis culture (Kappa = 0.200, AUC = 0.667) and acid-fast staining (Kappa = 0.154, AUC = 0.633). Ultrasound-guided percutaneous biopsy is a safe procedure. The GeneXpert MTB/RIF test has high sensitivity, specificity, and superior AUC value, which are of great value in the diagnosis of epididymal tuberculosis and rifampicin resistance detection.

Efficacy of pretomanid-containing regiments for drug-resistant tuberculosis: A systematic review and meta-analysis of clinical trials.

Concerns regarding the rise of drug-resistant tuberculosis (DR-TB) infections and the need for new drugs with shorter treatment time and fewer side effects have been voiced by the World Health Organization (WHO). The WHO revised its guideline to treat multidrug resistant tuberculosis (MDR-TB) with a 6-month course of BPaLM (bedaquiline, pretomanid, linezolid and moxifloxacin) in 2022. However, a thorough study and meta-analysis of available evidence is required due to the limited confidence of the evidence confirming the effectiveness of pretomanid-containing regiments. The aim of this systematic review and meta-analysis was to evaluate the effectiveness of pretomanid-containing regiments in treating DR-TB patients. Data from six search engines were searched using inclusion criteria based on the PICOS framework. The keywords of pretomanid and tuberculosis or their alternatives were used. Using RoB2 Cochrane risk-of-bias tool for randomized clinical trials, data were independently extracted and the quality of the data was evaluated. Odds ratio (OR) and heterogeneity tests were used and the findings were presented in ORs and forest plots. A total of four studies with 237 patients was included in the final analysis and 204 (86%) patients had favorable outcome (cured) and 33 (14%) was not cured. Pretomanid-containing regimen (OR: 46.73; 95%CI: 11.76-185.7) and BPaLM/BPaL (OR: 41.67; 95%CI: 8.86-196.73) regimens were associated with favorable outcome (cured). This meta-analysis indicates that the pretomanid-containing regimen and the BPaLM/BPaL regimen could increase the chance to have favorable outcome in DR-TB patients.

Identification of potential mutations associated with multidrug resistance among isolates of Mycobacterium tuberculosis in Malaysia by in silico screening

The emergence of multidrug resistance tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis (MTB) adaptation to survive in the presence of antibiotic, that were contributed by mutations in the MDR-associated genes. Previous research has indicated that the gene expression knockdown of fhaA leads to an accumulation of peptidoglycan (PG) precursors at the bacillary septum and poles, which suggest a possible deficiency in PG biosynthesis. Consequently, the cell wall becomes resistant to antibiotics, leading to multidrug resistance (MDR). In this study, bioinformatics analyses were performed on MDR-TB isolates from 24 clinical samples to search for novel mutations that contribute to antibiotic resistance. We found out a potential deletion of nucleotides encoding 6 amino acids in all 12 samples, particularly in fhaA gene (RV0020c). Our subsequent structural analysis shows that the deletion is at the position 243-248, causing conformational change of the native FhaA protein. We postulated that the deletion will potentially cause the loss of its binding affinity to MviN (precursor) and STPK (protein kinase), resulting in the inhibition and blockage of the peptidoglycan polymerization, causing MDR in MTB. In the future, experimental validation is necessitated to substantiate the association of these mutations with MDR.

Cellular Therapy with Autologous Mesenchymal Stromal Cells in Patients with Drug Resistant Pulmonary Tuberculosis

The objective: to evaluate the effectiveness of treatment with autologous mesenchymal stromal cells (MSCs) in patients with drug resistant pulmonary tuberculosis (DR TB).Subjects and Methods. 120 patients with drug resistant tuberculosis aged 18 to 61 years old were enrolled in the study. They all were treated at the Republican Scientific and Practical Center of Pulmonology and Phthisiology from 2009 to 2018. Against the background of anti-tuberculosis treatment, patients (60 people) from Main Group (MG) underwent bone marrow sampling and then intravenous administration of autologous MSCs.Results. The average dose of administered cells was 1x106 per kg of the patient body weight. The average duration of MSC cultivation made 35 days. Treatment effectiveness in MG made 90% versus 71% in Control Group (CG). All patients who were successfully cured of tuberculosis (TB) using autologous MSCs had no tuberculosis relapses during 5 years of follow-up. In Control Group, 8 (19%) cases of relapse were reported. In Main Group versus Comparison Group, the rates indicating healing of cavities and absence of relapse are statistically significantly better.Conclusion. The use of autologous MSCs in patients with drug resistant tuberculosis has shown its high effectiveness.

Evaluation of Effectiveness of 9- and 6-Month Treatment Regimens in Patients with Multiple Drug Resistant or Rifampicin-Resistant Tuberculosis in the Republic of Belarus

The objective: to evaluate the effectiveness of 39- and 24-week treatment regimens in patients with multiple drug resistant or rifampicin-resistant tuberculosis (MDR/RR-TB).Subjects and Methods. We evaluated the effectiveness of 39- and 24-week treatment regimens containing bedaquiline, levofloxacin, linezolid, clofazimine, and cycloserine or delamanid (modified short-course regimens - mSCR) and bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM), in cohorts of patients with MDR/RR-TB. Results. Of the 550 and 139 patients were included in the mSCR and SMARRTT Studies (BPaLM regimen) from December 2019 to October 2021 and from March 2022 to August 2022, 90.7% (487/537) and 94.2% (131/139) achieved a successful treatment outcome, respectively, 13 patients were excluded from the mSCR Study and continued treatment according to an individual regimen. Median (ME) and quartiles [Q1-Q3] of sputum culture conversion time in patients treated with mSCR and BPaLM made 30.0 (25.0-56.0) and 27.0 (25.0-29.8) days (p&lt;0.01) respectively. The prognostic factor for an unfavorable outcome for the BPaLM and mSCR regimens was a positive sputum microscopy result before treatment (OR – 7.92, 95% CI 1.5 – 41.0, p = 0.014; OR – 1.97, 95% CI 1.1–3.5, p=0.02, respectively), and for the mSCR regime, the time of sputum culture conversion &gt;90 days was an additional prognostic factor (OR – 3.35, 95% CI 1.2–9.5, p=0.03) .Conclusions. The effectiveness of the mSCR and BPaLM regimens in patients with MDR/RR-TB is high (90.7% and 94.2%, respectively). Patients with positive sputum microscopy and late sputum culture conversion have a lower chance of cure.

Monitoring the Cardiotoxic Effects of Bedaquiline in Older Children and Adolescents with Multiple and Extensive Drug Resistance

The objective: to evaluate expanded monitoring of cardiovascular disorders in older children and adolescents with multiple drug resistant tuberculosis receiving bedaquiline (Bq) as a part of anti-tuberculosis therapy.Subjects and Methods: A cohort retrospective-prospective study (2015-2021) was conducted, which included 36 patients aged 13-17 years old who received Bq. The prospective part included 19 patients (Main Group), they underwent extended monitoring (EM) of cardiotoxic reactions; this extended monitoring program was developed in Central Tuberculosis Research Institute. The retrospective part included 17 patients (Control Group), in whom cardiotoxic reactions were assessed using standard monitoring recommended by the Russian Society of Phthisiologists at that time. The relationship between the studied risk factor (monitoring by standard ECG) and the outcome (Bq discontinuation) was assessed using the Pearson χ2 test.Results. Prolongation of the QTc interval &gt; 0.440 ms was noted in 17.6% of cases in Control Group and it was regarded as a cardiotoxic effect of Bq, the drug was discontinued. In Main Group, prolongation was noted in 47.3% of cases which was considered a functional disorder of the cardiovascular system according to EM, the drug was not discontinued, χ2 = 3.896; p = 0.049. EM can be used in older children and adolescents with multiple drug resistant respiratory tuberculosis, which will make it possible to safely include Bq to chemotherapy regimens.

Delamanid: Safety and Efficacy Analysis

The review presents the analysis of 50 publications describing treatment of multiple drug resistant tuberculosis with regimens containing the new drug of delamanid. Delamanid possesses a dual bactericidal effect not only against active but also dormant Mycobacterium tuberculosis. The results of clinical studies on the efficacy and safety of delamanid within comprehensive chemotherapy are presented. The review demonstrates prospects for expanding the use of delamanid for treatment of adults and children.