Treatment Of Drug-resistant Tuberculosis Research Articles

Supporting tuberculosis program in active contact tracing: a case study from Pakistan

Tuberculosis (TB) is on the rise in Pakistan and there could be multiple reasons including poverty, difficulty in access to TB treatment services, non-compliance with treatment, social stigma etc. According to the TB program managers, limited treatment and testing sites for tuberculosis and lack of trained human resources play a major role in compromising TB management. A major lacuna in the TB control program is the absence of active contact tracing strategy. This is essential for a disease where positive cases are known to be able to infect a further 10‒15 individuals in a year. Tackling tuberculosis in Pakistan has been beleaguered by funding challenges and other systems’ bottlenecks such as lack of skilled human resources and insufficient supply of medicines, despite the fact that disease burden is one of the highest in the world. Although it is a notifiable disease, active case finding, contact tracing and reporting is notoriously low throughout the country. Access to diagnostics and treatment facilities has been limited and stigma attached to the disease remains deeply entrenched among the communities. Researchers have shown that enhanced and active approaches to contact investigation effectively identifies additional patients with TB among household contacts at a relatively modest cost. USAID’s Integrated Health Systems Strengthening and Service Delivery Activity extended support to the Health Departments of Sindh and Khyber Pakhtunkhwa provinces. In collaboration with the two provincial TB programs, community based active contact tracing was conducted on 17,696 individuals, based on the index cases. Among the contacts traced, 243 cases were diagnosed as drug sensitive or drug resistant TB. Awareness sessions were conducted to sensitize people on the various aspects of disease and importance of getting tested. The project also supported establishing three satellite Programmatic Management of Drug Resistant Tuberculosis (PMDT) sites for drug resistant TB treatment, enhancing the programs’ diagnostic and testing capacity.

A Clinical Case of the Personalized Approach to Surgical Treatment of Drug-Resistant Bilateral Fibrous Cavernous Pulmonary Tuberculosis Complicated by Pyopneumothorax and Pleural Cavity Empyema

A clinical case shows the complexity of the choice of surgical strategy for treatment in drug-resistant bilateral fibrous cavernous pulmonary tuberculosis complicated by pyopneumothorax and empyema of the pleural cavity. A non-standard personalized approach to the patient with initially compromised cardiorespiratory system resulted not only in cure of tuberculosis complications but also improved pulmonary functional parameters and allowed avoiding progression of pulmonary tuberculosis.

РЕЗУЛЬТАТЫ ПРИМЕНЕНИЯ КОМБИНИРОВАННОЙ ПРОБИОТИЧЕСКОЙ ТЕРАПИИ ДЛЯ КОРРЕКЦИИ НАРУШЕНИЙ МИКРОБИОЦЕНОЗА КИШЕЧНИКА БОЛЬНЫХ ТУБЕРКУЛЕЗОМ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙ- ЧИВОСТЬЮ ВОЗБУДИТЕЛЯ

Introduction. About 90% of TB patients have side effects of anti-TB therapy in the form of gastrointestinal disorders. Currently, the role of disorders of the intestinal microbiocenosis in the formation of dyspepsia has been proven. In turn, dyspeptic syndrome leads to a decrease in patient adherence to treatment, which affects the effectiveness of tuberculosis treatment. The most dangerous in this regard are second-line anti-tuberculosis drugs used in the treatment of drug-resistant tuberculosis. Long-term use of these drugs requires the development and implementation of algorithms for the correction of microecological disorders of the intestine. The aim of the study was to evaluate the microbiological results of using a combined probiotic in persons with tuberculosis and multidrug-resistant pathogen in the course of anti-tuberculosis therapy. Material and methods. A prospective linear study included 30 patients with respiratory tuberculosis and multidrug-resistant pathogen. The study consisted in a two-stage study of the microbiocenosis of the intestinal biotope of these patients by a quantitative bacteriological method before and after combined probiotic therapy with a further comparison of the number of microorganisms. Statistical data processing was performed using the IBM SPSS program. Qualitative signs are represented by absolute and relative frequencies, expressed as a percentage, with 95% confidence intervals calculated for them by the Wilson method (rel.% [95% CI]). Quantitative data are presented in the work in the format of the median and interquartile range (Me (25th; 75th). For variables related to the ordinal scale and nonparametric quantitative variables, the Mann-Whitney U test was used to compare the two groups of observations. the compared groups were considered statistically significant with a statistical significance of less than 0.05. Results and discussion. The use of combined probiotic therapy in patients with multidrug-resistant tuberculosis did not compensate for the deficiency of obligate microorganisms - Bifidobacterium spp., Lactobacillus spp. However, in the process of probiotic therapy noted a decrease in the concentration of Enterococcus spp., E. Coli lac-, E. Coli hly +, Streptococcus spp., as well as a decrease in the titers and species structure of fungi of the genus Candida. A clinical example showing the microbiological and clinical efficacy of probiotic therapy in a patient with co-infection TB / HIV. Despite the changes received, the average population indicators for the region have not been achieved. Conclusion. It was found that the use of combined probiotic therapy in patients with multidrug-resistant tuberculosis led to a decrease in the pool of opportunistic microorganisms in the intestinal lumen and had a positive clinical effect in a patient with TB / HIV co-infection.

Low BMI increases all-cause mortality rates in patients with drug-resistant TB.

BACKGROUND: Loss to follow-up (LTFU) is common among patients with drug-resistant TB (DR-TB) receiving second-line TB treatment; however, little is known about outcomes after LTFU, including mortality.OBJECTIVE: To determine rates of and factors associated with all-cause mortality among patients with DR-TB who were LTFU.METHODS: Retrospective cohort study of adult patients with DR-TB in Georgia who initiated second-line TB treatment during 2011-2014 and were LTFU. Survival analyses were used to estimate all-cause mortality rates and adjusted hazard ratios (aHR).RESULTS: During 2011-2014, 2,437 second-line treatment episodes occurred and 695 patients were LTFU. Among 695 LTFU patients, 143 (21%) died during 2,686 person-years (PY) post-LTFU (all-cause mortality rate 5.1%, 95% CI 4.3-6.0 per 100 PY). In multivariable analysis, low weight (BMI < 18.5 kg/m²) at treatment initiation (aHR 3.2, 95% CI 2.2-4.7), return to treatment after LTFU (aHR 3.1, 95% CI 2.2-4.4), <12 months of treatment (aHR 2.4, 95% CI 1.4-4.1) and a pre-LTFU positive culture (aHR 3.3, 95% CI 2.2-4.9) were associated with all-cause mortality.CONCLUSION: High all-cause mortality occurred among patients with DR-TB after LTFU despite a low HIV prevalence. Providing additional assistance for patients during DR-TB treatment to prevent LTFU and use of new and shorter treatment regimens may reduce mortality among LTFU.

A longitudinal community-based ototoxicity monitoring programme and treatment effects for drug-resistant tuberculosis treatment, Western Cape.

BackgroundSouth Africa has a high burden of drug-resistant tuberculosis (DRTB) and until recently, ototoxic aminoglycosides were predominant in treatment regimens. Community-based ototoxicity monitoring programmes (OMPs) have been implemented for early detection of hearing loss and increased patient access.ObjectivesA longitudinal study was conducted to describe the service delivery characteristics of a community-based OMP for DRTB patients facilitated by CHWs as well as observed ototoxic hearing loss in this population.MethodA descriptive retrospective record review of longitudinal ototoxicity monitoring of 194 DRTB patients undergoing treatment at community-based clinics in the city of Cape Town between 2013 and 2017.ResultsFollow-up rates between consecutive monitoring assessments reached as high as 80.6% for patients assessed by CHWs. Few patients (14.2% – 32.6%) were assessed with the regularity (≥ 6 assessments) and frequency required for effective ototoxicity monitoring, with assessments conducted, on average, every 53.4–64.3 days. Following DRTB treatment, 51.5% of patients presented with a significant ototoxic shift meeting one or more of the American Speech-Language-Hearing Association (ASHA) criteria. Deterioration in hearing thresholds was bilateral and most pronounced at high frequencies (4 kHz – 8 kHz). The presence of pre-existing hearing loss, human immunodeficiency virus co-infection and a history of noise exposure were significant predictors of ototoxicity in patients.ConclusionDRTB treatment with kanamycin resulted in significant deterioration of hearing longitudinally, predominantly at high frequencies. With ongoing training and supportive supervision, CHWs can facilitate community-based ototoxicity monitoring of DRTB patients. Current protocols and guidelines may require reassessment for appropriate community-based ototoxicity monitoring.

Model-Informed Precision Dosing of Linezolid in Patients with Drug-Resistant Tuberculosis.

Linezolid is an efficacious medication for the treatment of drug-resistant tuberculosis but has been associated with serious safety issues that can result in treatment interruption. The objectives of this study were thus to build a population pharmacokinetic model and to use the developed model to establish a model-informed precision dosing (MIPD) algorithm enabling safe and efficacious dosing in patients with multidrug- and extensively drug-resistant tuberculosis. Routine hospital therapeutic drug monitoring data, collected from 70 tuberculosis patients receiving linezolid, was used for model development. Efficacy and safety targets for MIPD were the ratio of unbound area under the concentration versus time curve between 0 and 24 h over minimal inhibitory concentration (fAUC0–24h/MIC) above 119 and unbound plasma trough concentration (fCmin) below 1.38 mg/L, respectively. Model building was performed in NONMEM 7.4.3. The final population pharmacokinetic model consisted of a one-compartment model with transit absorption and concentration- and time-dependent auto-inhibition of elimination. A flat dose of 600 mg once daily was appropriate in 67.2% of the simulated patients from an efficacy and safety perspective. Using the here developed MIPD algorithm, the proportion of patients reaching the efficacy and safety target increased to 81.5% and 88.2% using information from two and three pharmacokinetic sampling occasions, respectively. This work proposes an MIPD approach for linezolid and suggests using three sampling occasions to derive an individualized dose that results in adequate efficacy and fewer safety concerns compared to flat dosing.

Acquired bedaquiline resistance during the treatment of drug-resistant tuberculosis: a systematic review.

BackgroundDrug-resistant tuberculosis (DR-TB) is considered to be a public health threat and is difficult to cure, requiring a lengthy treatment with potent, potentially toxic drugs. The novel antimicrobial agent bedaquiline has shown promising results for patients with DR-TB, improving the rate of culture conversion and reducing TB-related mortality. However, increasing numbers of cases with acquired bedaquiline resistance (ABR) have been reported in recent years.MethodsThis systematic review aimed to assess the frequency of ABR and characteristics of patients acquiring it. Studies showing data on sequential bedaquiline drug-susceptibility testing in patients treated with a bedaquiline-containing regimen were included. The databases CENTRAL, PubMed and Embase were manually searched, and 866 unique records identified, eventually leading to the inclusion of 13 studies. Phenotypic ABR was assessed based on predefined MIC thresholds and genotypic ABR based on the emergence of resistance-associated variants.ResultsThe median (IQR) frequency of phenotypic ABR was 2.2% (1.1%–4.6%) and 4.4% (1.8%–5.8%) for genotypic ABR. Among the studies reporting individual data of patients with ABR, the median number of likely effective drugs in a treatment regimen was five, in accordance with WHO recommendations. In regard to the utilization of important companion drugs with high and early bactericidal activity, linezolid was included in the regimen of most ABR patients, whereas the usage of other group A (fluoroquinolones) and former group B drugs (second-line injectable drugs) was rare.ConclusionsOur findings suggest a relevant frequency of ABR, urging for a better protection against it. Therefore, treatment regimens should include drugs with high resistance-preventing capacity through high and early bactericidal activity.

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.

Impact of Treatment Supporters on the Treatment Outcomes of Drug Resistant-Tuberculosis (DR-TB) Patients: A Retrospective Cohort Study.

Background: Drug resistant-tuberculosis (DR-TB) patients are provided universal drug susceptibility testing (UDST), anti-TB drugs for the treatment of DR-TB, nutritional support (Nikshay Poshan Yojana - the financial incentive of rupees five hundred per month for each notified DR-TB patient for the duration for which the patient is on anti-TB drugs) by the Government of India.Methods: This retrospective cohort record-based study was conducted in DR-TB patients. Some 1095 DR-TB patients who have initiated treatment at Nodal DR-TB Centre, Darbhanga Medical College and Hospital (DMCH), Darbhanga, and continued their anti-TB drugs at home blocks were followed till their treatment outcome was known. Data were analyzed by statistical experts of DMCH.Results: Treatment supporters comprised 688 (62.83%) females and 407 (37.17%) males. Different types of treatment supporters noted were accredited social health activists (ASHAs) 622 (56.80%), family members 365 (33.33%), and community health workers 108 (09.86%). Treatment outcome as transfer out was observed in 08 (1.29%), 10 (2.74%), and 13 (12.03%) cases among ASHAs, family members, and community health workers, respectively [statistically significant (p < 0.0001)].Conclusion: ASHAs proved to be the best treatment supporters in comparison to both family members and community health workers for multi-drug resistant TB (MDR/RR-TB) patients.

A treatment recommender clinical decision support system for personalized medicine: method development and proof-of-concept for drug resistant tuberculosis

BackgroundPersonalized medicine tailors care based on the patient’s or pathogen’s genotypic and phenotypic characteristics. An automated Clinical Decision Support System (CDSS) could help translate the genotypic and phenotypic characteristics into optimal treatment and thus facilitate implementation of individualized treatment by less experienced physicians.MethodsWe developed a hybrid knowledge- and data-driven treatment recommender CDSS. Stakeholders and experts first define the knowledge base by identifying and quantifying drug and regimen features for the prototype model input. In an iterative manner, feedback from experts is harvested to generate model training datasets, machine learning methods are applied to identify complex relations and patterns in the data, and model performance is assessed by estimating the precision at one, mean reciprocal rank and mean average precision. Once the model performance no longer iteratively increases, a validation dataset is used to assess model overfitting.ResultsWe applied the novel methodology to develop a treatment recommender CDSS for individualized treatment of drug resistant tuberculosis as a proof of concept. Using input from stakeholders and three rounds of expert feedback on a dataset of 355 patients with 129 unique drug resistance profiles, the model had a 95% precision at 1 indicating that the highest ranked treatment regimen was considered appropriate by the experts in 95% of cases. Use of a validation data set however suggested substantial model overfitting, with a reduction in precision at 1 to 78%.ConclusionOur novel and flexible hybrid knowledge- and data-driven treatment recommender CDSS is a first step towards the automation of individualized treatment for personalized medicine. Further research should assess its value in fields other than drug resistant tuberculosis, develop solid statistical approaches to assess model performance, and evaluate their accuracy in real-life clinical settings.

Drug-resistant tuberculosis: advances in diagnosis and management.

Purpose of reviewDiagnosis and treatment of drug-resistant tuberculosis (DR-TB) is undergoing substantial changes, owing availability of new diagnostic tools and drugs, coupled with global underdiagnosis and undertreatment. Recent developments are reviewed.Recent findingsMolecular diagnostics, for Mycobacterium tuberculosis complex detection and prediction of drug resistance, implemented in the last decade, accelerated TB diagnosis with improved case detection. Nevertheless, access and coverage of drug-resistance testing remain insufficient. Genome sequencing-technologies, based on targeted next-generation sequencing show early potential to mitigate some of the challenges in the future. The recommendation to use an all oral, bedaquiline based regimen for treatment of multidrug-resistant/rifampicin-resistant TB is major advancement in DR-TB care. TB regimen using new and repurposed TB drugs demonstrate in recent clinical trials like, NIX-TB, ZeNIX and TB PRACTECAL considerable treatment success, shorten treatment duration and reduce toxicity. Their optimal use is threatened by the rapid occurrence and spread of strains, resistant to new drugs. Children benefit only very slowly from the progress.SummaryThere is notable progress in improved diagnosis and treatment of drug-resistant TB, but complicated by the COVID-19 pandemic the majority of TB patients worldwide don’t have (yet) access to the advances.

Psychiatric comorbidities among patients with complex drug-resistant tuberculosis in Mumbai, India.

BackgroundPeople with drug-resistant tuberculosis (DR-TB) are known to suffer from many mental-health disorders. This study aims to describe the proportion of patients diagnosed with psychiatric comorbidities, the different psychiatric diagnoses made, and treatment outcomes among DR-TB patients with or without psychiatric comorbidity and initiated on DR-TB treatment between January 2012 and March 2019 at Médecins Sans Frontières independent clinic in Mumbai, India.MethodsThis is a retrospective study using routinely collected clinical data. DR-TB care included individualised treatment, psychosocial support, and integrated psychiatric care.ResultsDuring the study period, 341 DR-TB patients were enrolled, with a median age of 25 years (IQR:20.0–36.5 years), 185 (54.2%) females, 143 (41.9%) with PreXDR-TB, and 140 (41.0%) with XDR-TB. All 341 patients were screened by a counsellor, 119 (34.9%) were referred for psychiatric evaluation, and 102 (29.9% of 341) were diagnosed with a psychiatric comorbidity. Among 102 diagnosed with a psychiatric comorbidity, 48 (47.0%) were diagnosed at baseline, and 86 (84.3%), or 25.2% of all 341 patients enrolled, were treated with psychotropic drugs. Depressive disorders were diagnosed in 49 (48.0%), mixed anxiety and depression in 24 (23.5%), neurocognitive disorders and anxiety in five (4.9%), and medication induced psychosis in two (2.0%). No anti-TB drugs were significantly associated with psychiatric comorbidities developed during treatment. Of 102 DR-TB patients with a psychiatric comorbidity, 75.5% (77) had successful DR-TB treatment outcomes, compared to 61.1% (146/239) not diagnosed with a psychiatric comorbidity (p = 0.014).ConclusionIn our setting, among people started on DR-TB treatment, and with a complex TB resistance profile, about one in three patients experienced a psychiatric comorbidity, of which half developed this comorbidity during treatment. With comprehensive psychiatric care integrated into DR-TB care delivery, treatment outcomes were at least as good among those with psychiatric comorbidities compared to those without such comorbidities.

Safety and Efficacy of Multiple Drug Resistant Tuberculosis Treatment in Patients with Different HIV Statuses

The objective: to analyze and compare frequency and variety of adverse events (AEs) and their impact on outcomes of tuberculosis therapy when treating patients with multiple drug resistant tuberculosis (MDR TB) and different HIV statuses.Subjects and Methods: retrospective observational case-control study of patients registered for treatment with the 4th regimen of chemotherapy for tuberculosis in the city of Vladimir and Vladimir Region in 2014-2016.Results. The proportion of patients who reported any AE during the MDR TB treatment was similar among HIV positive and HIV negative patients and made 85.5%. In patients with concurrent HIV infection and MDR TB, hematopoietic AEs such as anemia, thrombocytopenia were more frequent, while neutropenia was significantly more frequent when comparing groups by the cumulative event probability method. Elevated eosinophil level during treatment was more typical of MDR TB patients. Treatment outcomes in the group of patients with HIV and MDR TB were statistically significantly worse due to the higher frequency of fatal outcomes. At the same time, there was no correlation of AE with unfavorable treatment outcomes. The early initiation of combination therapy with thorough monitoring of hematologic parameters in patients with HIV and MDR TB was safe and effective.

Clinical guidelines for managing hearing loss as a complication of drug-resistant tuberculosis treatment: an evaluation of implementation fidelity in Kano, Nigeria

BackgroundNigeria has a high burden of Tuberculosis (TB) including Drug-resistant Tuberculosis (DR-TB) and hearing loss. Despite several efforts directed toward its control, many patients fail to respond to treatment, having developed DR-TB. Lack of adherence to the DR-TB guidelines/improper implementation of the guideline has been identified as one of the factors impeding on effective treatment. This study sought to measure the implementation fidelity of health workers to management guidelines for hearing loss resulting from DR-TB treatment and to identify its determinants.MethodA questionnaire-based cross-sectional study was conducted at the Infectious Disease Hospital, Kano. Implementation fidelity of the Programmatic Management guidelines for the treatment of Drug-resistant Tuberculosis was measured under the four domains of content, coverage, duration and frequency. The determinants examined are intervention complexity, facilitation strategies, quality of delivery and participant responsiveness as proposed by the Carroll et al. framework. Other determinants used are age, sex, professional cadre and work experience of healthcare providers.ResultsThe Implementation fidelity score ranged from 40 to 64% with a mean of 47.6%. Quality of delivery, intervention complexity, participants’ responsiveness, and being a medical doctor exerted a positive effect on implementation fidelity while facilitation strategy, age and work experience exerted a negative effect on implementation fidelity.ConclusionThe implementation fidelity of management guidelines for hearing loss resulting from DR-TB treatment was low. Implementation fidelity should be assessed early and at intervals in the course of implementing the Programmatic Management of Drug-resistant Tuberculosis guideline and indeed, in the implementation of any intervention.

Treating children with tuberculosis—Using pharmacometrics to do better

Treating children with tuberculosis—Using pharmacometrics to do better

Optimized Loading Dose Strategies for Bedaquiline When Restarting Interrupted Drug-Resistant Tuberculosis Treatment.

Interruption of treatment is common in drug-resistant tuberculosis patients. Bedaquiline has a long terminal half-life; therefore, restarting after an interruption without a loading dose could increase the risk of suboptimal treatment outcome and resistance development. We aimed to identify the most suitable loading dose strategies for bedaquiline restart after an interruption. A model-based simulation study was performed. Pharmacokinetic profiles of bedaquiline and its metabolite M2 (associated with QT prolongation) were simulated for 5,000 virtual patients for different durations and starting points of treatment interruption. Weekly bedaquiline area under the concentration-time curve (AUC) and M2 maximum concentration (Cmax) deviation before interruption and after reloading were assessed to evaluate the efficacy and safety, respectively, of the reloading strategies. Bedaquiline weekly AUC and M2 Cmax deviation were mainly driven by the duration of interruption and only marginally by the starting point of interruption. For interruptions with a duration shorter than 2 weeks, no new loading dose is needed. For interruptions with durations between 2 weeks and 1 month, 1 month and 1 year, and longer than 1 year, reloading periods of 3 days, 1 week, and 2 weeks, respectively, are recommended. This reloading strategy results in an average bedaquiline AUC deviation of 1.88% to 5.98% compared with -16.4% to -59.8% without reloading for interruptions of 2 weeks and 1 year, respectively, without increasing M2 Cmax. This study presents easy-to-implement reloading strategies for restarting a patient on bedaquiline treatment after an interruption.

Introduction of BPaL for the treatment of drug resistant tuberculosis in the Kyrgyz Republic

Introduction of BPaL for the treatment of drug resistant tuberculosis in the Kyrgyz Republic

An Overview of Zinc Oxide Nanoparticles Produced by Plant Extracts for Anti-tuberculosis Treatments.

Tuberculosis (TB), induced by Mycobacterium tuberculosis (MTB), is a fatal infectious disease that kills millions of lives worldwide. The emergence of drug-resistant and multidrug-resistant cases is regarded as one of the most challenging threats to TB control due to the low cure rate. Therefore, TB and drug-resistant TB epidemic urge us to explore more effective therapies. The increasing knowledge of nanotechnology has extended the use of some nanomedicines for disease treatment in clinics, which also provide novel possibilities for nano-based medicines for TB treatment. Zinc oxide nanoparticles (ZnO NPs) have gained increasing attention for anti-bacterial uses based on their strong ability to induce reactive oxidative species (ROS) and release bactericidal Zinc ions (Zn2+), which are expected to act as novel strategies for TB and drug-resistant TB treatment. Some plant extracts, always from active herbal medicines, have been widely reported to show attractive anti-bacterial activity for infectious treatment, including TB. Here, we summarize the synthesis of ZnO NPs using plant extracts (green synthesized ZnO NPs), and further discuss their potentials for anti-TB treatments. This is the first review article discussing the anti-TB activity of ZnO NPs produced using plant extracts, which might contribute to the further applications of green synthesized ZnO NPs for anti-TB and drugresistant TB treatment.

The efficacy of drug resistant tuberculosis treatment in patients with different comorbidity status

Introduction. The efficacy of multidrug resistant (MDR) and extensive drug resistance (XDR) tuberculosis (TB) therapy is not yet resolved up to now. New regimens including tioureidoiminomethylpyridinium perchlorate (Tpp) and bedaquiline (Bq) can improve the efficacy of treatment, but due to the growing comorbidities and lack of comprehensive assessment of their severity it is difficult to define the impact of such comorbidities on the efficacy of treatment in this cohort of patients. Ма-terials and methods. Retrospective study has been conducted to review the efficacy of therapy in MDR and XDR TB patients from 18 years of age and with bacteri-al excretion (n=303), who received therapy from 2016 tо 2019. Patients were divided into two main groups: Group I — patients with MDR TB (n=153); Group II — pa-tients XDR TB (n=150). Statistical analysis of the results was carried out via Statistica 10.0 and SPSS 16.0 &amp; Graph-Pad Prism 6 software. Spearman’s correlation coefficient was applied, with meaningful p≤0.05. Results. Theeffi-cacy of therapywas statistically significant higher in MDR TB patients (66.7% vs 40.7%, where χ2=20.6, р&lt;0.01), meanwhile XDR TB patients on the background of low efficacy of treatment show significantly high percent of defaulted treatment (16.7% vs 3.9%, where χ2=13.4, р&lt;0.01). Comorbidity impacts of therapy in XDR TB pa-tients’ treatment especially chronic liver pathology and gastrointestinal diseases (GIT). However, applying Tpp and Bq in scheme of therapy, the treatment outcomes in XDR TB patients with Charlson comorbidity index (ChI) from 3 to 4 improved in 44,8 и 41,1% of cases respec-tively. Conclusions. XDR TB patients are the most severe group of patients in terms of comorbidities that contrib-ute to the low efficacy of treatment. Applying of Tpp and Bq in scheme of therapy allows to efficacy of treatment in 44,8 и 41,1% of cases respectively in severe comorbid-ity patients. It is recommended to use in scheme of ther-apy new anti-TB drugs (Tpp and Bq) after examination of chronic liver pathology and GIT diseases.

ЭФФЕКТИВНОСТЬ ЛЕЧЕНИЯ ТУБЕРКУЛЕЗА У ПАЦИЕНТОВ С РАЗЛИЧНЫМИ СРОКАМИ АМБУЛАТОРНОГО И СТАЦИОНАРНОГО ЭТАПОВ ЛЕЧЕНИЯ

Access to timely diagnosis and patient-friendly drug-resistant TB treatment regimens is a priority in the fight against TB. The aim of the work is to improve the efficiency of treatment of patients with tuberculosis in outpatient and inpatient settings by developing a new procedure for the provision of antituberculosis care. Materials and methods. The object of a retrospective cohort study was 15617 patients with tuberculosis who underwent treatment in the period 2015-2019. Results and discussion. Despite the annual decrease in the total number of reported cases of tuberculosis, the pattern of cases of multidrug-resistant tuberculosis has a heterogeneous trend. There has been a decrease in the proportion of MDR-TB cases among previously treated cases and an increase in new cases. There is an increase in the proportion of cases that successfully completed treatment in all patient cohorts. Conclusion. The main number of losses for follow-up is recorded at the outpatient stage of treatment, which is associated with problems in the formation of patient adherence to treatment, as well as with insufficient quality management and clinical and laboratory tracking of adverse drug events. Bed efficiency indicators for the treatment of MDR-TB patients indicate insufficient bed efficiency.