Pulmonary Multidrug-resistant Tuberculosis Research Articles

A complex case study: coexistence of multi-drug-resistant pulmonary tuberculosis, HBV-related liver failure, and disseminated cryptococcal infection in an AIDS patient

BackgroundHepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates.Case presentationThe 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient’s condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management.ConclusionEnhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.

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

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

Modelling Time to Recovery from Multidrug Resistant Tuberculosis in Southern Ethiopia

Introduction: Multidrug resistant tuberculosis (MDR-TB) is a global heath threat, resistant to key anti-TB drugs. It is ranked among the top 10 causes of death worldwide. Therefore, the current study investigated time to recovery from MDR-TB in southern Ethiopia. Data, Materials and Methods: Restrospective data from selected hospitals in SNNPR (January 2016 to December 2021) were analyzed. A cluster sample of 301 MDR-TB patients (131 NEMMCH, 121 BH, 49 AGH) was considered. Results: Among the 301 cases, 116 (38.5%) were censored. While 185 (61.5%) were recovered. Parametric shared frailty models were employed to account unobserved heterogeneity among the Hospitals and patients and AFT models were employed. the median recovery time of MDR-TB is 22 months. The clustering effect of frailty model was hospitals. Weibull-gamma shared frailty model was appropriate for this data. Conclusion: The final model showed that males have higher recovery rates than females. Extra pulmonary MDR-TB and Urban residency correleted with longer recovery times. The recovery rate increases with increasing baseline weight, education level, and occupation. But, the recovery rate decreases with smoking, co-morbidities, previous drug history, history of TB, and alcohol use Recommendation: All concerned bodies should be cognizant on the risk factors of MDR-TB in SNNP region By providing on early case detection and appropriate treatment of drug-susceptible MDR-TB, since it is essential to shorten the recovery time of MDR-TB patients in line with WHO guidelines

Survival Probability in Multidrug Resistant Pulmonary Tuberculosis Patients in a South Indian Region

Background: Drug-resistant tuberculosis is a burgeoning threat to public health requiring novel strategies to combat the infection. Although national tuberculosis elimination programs focus on improving health services, challenges in eradicating tuberculosis still exist. Factors attributing to unfavorable outcomes are unknown in Warangal district of Telangana state. Methods: This study included 296 patients diagnosed with multidrug-resistant pulmonary tuberculosis. The study participants followed up for a maximum of 20 months to determine treatment outcomes. Statistical applications of Kaplan-Meier curve and log-rank test used to find the survival probabilities in subgroups. Results: The survival of multidrug-resistant pulmonary tuberculosis patients was ascertained, in male and female patients, aged between 31 and 50 years. Resistance to rifampicin was prominent. The study found a survival rate of 76.68% and a mortality rate of 23.31%. The log-rank test revealed a significant difference in survival in subcategories with and without comorbidities ( P = .03), non-adherence to treatment ( P = .0001), treatment duration ( P = .02), regimens ( P = .01), and grading of radiograph ( P = .0001). Conclusion: This study identified factors that influenced the survival probability of multidrug-resistant pulmonary tuberculosis patients, including comorbidities, weight band, non-adherence to treatment, treatment duration, regimens, and grading of radiograph. These findings emphasize the need for enhanced management strategies to improve treatment outcomes.

Study of Culture Conversion in Drug-Resistant Pulmonary Tuberculosis on All-Oral Longer Regimen at IGIMS, Patna

ABSTRACT Background: Multidrug-resistant tuberculosis (MDR-TB) refers to tuberculosis that resists at least two primary drugs, namely isoniazid and rifampicin. To assess the management of MDR-TB, sputum culture conversion is performed. This study aimed to determine the culture conversion status of MDR-TB patients undergoing an all-oral longer regimen. Methods: This research constitutes an observational and prospective study conducted within a hospital setting. The study was done at the Department of Microbiology, IGIMS, Patna, from October 2020 to March 2022. Culture conversion in multidrug resistance pulmonary tuberculosis on all-oral longer regimens took one spot and one morning sample of sputum as per standard protocol after completing two months of all-oral longer regimens and culturing it in liquid broth using Mycobacterium Growth Indicator Tube (MGIT) 960 System at two, four then six months till we got a negative result. Results: Maximum number of the cases, 77 (74.8%), belonged to 19–35 years of age group. Males were 68 (66.1%) and females were 35 (33.9%), respectively, with male to female ratio of 1.9:1. After 2 months of oral longer regimen treatment, out of 103 cases, we found 98 (95.1%) patients had sputum for culture positive and only five (4.2%) patients had sputum for culture negative. After 6 months of oral longer regimen treatment, out of 101 cases, we found 16 (15.8%) patients had sputum for culture positive and 85 (85.2%) patients had sputum for culture negative. Conclusion: In patients with multidrug-resistant pulmonary tuberculosis (MDR-TB) who received an all-oral longer regimen, the introduction of bedaquiline led to positive outcomes as evidenced by a greater number of negative sputum cultures, a decrease in culture reversions, and a reduced risk of developing a more resistant form of MDR-TB.

Development of a self-microemulsifying drug delivery system to deliver delamanid via a pressurized metered dose inhaler for treatment of multi-drug resistant pulmonary tuberculosis

Tuberculosis (TB) is a serious health issue that contributes to millions of deaths throughout the world and increases the threat of serious pulmonary infections in patients with respiratory illness. Delamanid is a novel drug approved in 2014 to deal with multi-drug resistant TB (MDR-TB). Despite its high efficiency in TB treatment, delamanid poses delivery challenges due to poor water solubility leading to inadequate absorption upon oral administration. This study involves the development of novel formulation-based pressurized metered dose inhalers (pMDIs) containing self-microemulsifying mixtures of delamanid for efficient delivery to the lungs. To identify the appropriate self-microemulsifying formulations, ternary diagrams were plotted using different combinations of surfactant to co-surfactant ratios (1:1, 2:1, and 3:1). The combinations used Cremophor RH40, Poly Ethylene Glycol 400 (PEG 400), and peppermint oil, and those that showed the maximum microemulsion region and rapid and stable emulsification were selected for further characterization. The diluted self-microemulsifying mixtures underwent evaluation of dose uniformity, droplet size, zeta potential, and transmission electron microscopy. The selected formulations exhibited uniform delivery of the dose throughout the canister life, along with droplet sizes and zeta potentials that ranged from 24.74 to 88.99 nm and − 19.27 to − 10.00 mV, respectively. The aerosol performance of each self-microemulsifying drug delivery system (SMEDDS)-pMDI was assessed using the Next Generation Impactor, which indicated their capability to deliver the drug to the deeper areas of the lungs. In vitro cytotoxicity testing on A549 and NCI-H358 cells revealed no significant signs of toxicity up to a concentration of 1.56 µg/mL. The antimycobacterial activity of the formulations was evaluated against Mycobacterium bovis using flow cytometry analysis, which showed complete inhibition by day 5 with a minimum bactericidal concentration of 0.313 µg/mL. Moreover, the cellular uptake studies showed efficient delivery of the formulations inside macrophage cells, which indicated the potential for intracellular antimycobacterial activity. These findings demonstrated the potential of the Delamanid-SMEDDS-pMDI for efficient pulmonary delivery of delamanid to improve its effectiveness in the treatment of multi-drug resistant pulmonary TB.

Particulate matter deposition and its impact on tuberculosis severity: A cross-sectional study in Taipei

The objective of this study was to examine the association between the lung lobe-deposited dose of inhaled fine particulate matter (PM2.5) and chest X-ray abnormalities in different lung lobes of pulmonary tuberculosis (TB), multidrug-resistant tuberculosis (MDR-TB), and non-tuberculosis mycobacteria infections (NTM). A cross-sectional study was conducted between 2014 and 2022, comprising 1073 patients who were recruited from chest department clinic in a tertial refer hospital in Taipei City, Taiwan. Ambient 1-, 7-, and 30-day PM2.5 exposure and the deposition of PM2.5 in different lung lobes were estimated in each subject. The β coefficient for PM2.5 and deposited PM2.5 in lungs with the outcome variables (pulmonary TB, MDR-TB, and NTM infection) was derived through regression analysis and adjusted for age, gender, BMI, smoking status, and family income. We observed that a 1 μg/m3 increase in ambient PM2.5 was associated with an increase of MDR-TB infections of 0.004 times (95%CI: 0.001–0.007). A 1 μg/m3 increase in 1-day and 7-day PM2.5 deposition in left upper lobe and left lower lobe was associated with an increase in chest X-ray abnormalities of 9.19 % and 1.18 % (95%CI: 0.87–17.51 and 95%CI: 0.08–2.28), and 4.52 % and 5.20 % (95%CI: 0.66–8.38 and 95%CI: 0.51–9.89) in left lung of TB patients, respectively. A 1 μg/m3 increase in 30-day PM2.5 deposition in alveolar region was associated with an increase in percent abnormality of 2.50 % (95%CI: 0.65–4.35) in left upper lobe and 3.33 % (95%CI: 0.65–6.01) in right middle lobe, while in total lung was 0.63 % (95%CI: 0.01–1.27) in right upper lobe and 0.37 % (95%CI, 0.06–0.81) in right lung of MDR-TB patients. Inhaled PM2.5 deposition in lungs was associated with an exacerbation of the radiographic severity of pulmonary TB, particularly in pulmonary MDR-TB patients in upper and middle lobes. Particulate air pollution may potentially exacerbate the radiographic severity and treatment resistance in individuals with pulmonary TB.

Drug Resistance Tests for Mycobacterium Tuberculosis and Compatibility between Tests; From Past to Today

Objective: The gold standard for pulmonary tuberculosis diagnosis is the demonstration of Mycobacterium tuberculosis bacilli. Drug susceptibility test results of the bacilli obtained are crucial in tuberculosis treatment management. The various tests used to determine drug susceptibility must yield the same result. In the present study, we aimed to evaluate the compatibility of drug susceptibility test results obtained by Löwenstein-Jensen (L-J) and BACTEC 460TB methods from the past to the present. Material and Methods: Sputum results from 79 patients suspected of multidrug-resistant pulmonary tuberculosis (MDR-TB) clinically, radiologically, and bacteriologically were evaluated for isoniazid, rifampicin, ethambutol, and streptomycin between June 1997 and June 1998. Culture and drug sensitivity tests on the L-J medium were conducted at the Heybeliada Chest Diseases and Thoracic Surgery Center bacteriology laboratory, while culture and drug sensitivity tests with the BACTEC 460 TB system were performed at another center. The results were assessed for compatibility using the Kappa (κ) test, a tool for comparing two independent parameters. Results: All drug sensitivity tests for isoniazid, rifampicin, ethambutol, and streptomycin were collectively evaluated. It was determined that 263 (83.3%) of 316 drug sensitivity tests yielded concordant results, while 53 (16.7%) produced discordant results. The drug sensitivity tests using L-J and BACTEC 460TB methods indicated compatibility only for streptomycin (κ = 0.715). In contrast, they yielded different results for isoniazid (κ = 0.585), ethambutol (κ = 0.552), and rifampicin (κ = 0.507). Streptomycin exhibited compatibility, while isoniazid, ethambutol, and rifampicin showed incompatibility between the L-J and BACTEC 460TB methods. Conclusion: Drug sensitivity tests are pivotal in tuberculosis treatment management. While literature suggests compatibility between L-J and BACTEC 460TB methods, our study revealed incompatibility. Evaluation of drug sensitivities may lead to confusing results. Current practices involving studies in the same laboratory and genetic testing contribute to faster and more accurate outcomes in managing drug-resistant tuberculosis. Genetic tests and reference laboratories remain crucial for antituberculosis drug sensitivity, emphasizing their continued importance.

Case report of septic pulmonary embolism caused by Staphylococcus aureus combined with multidrug-resistant pulmonary tuberculosis and bronchial tuberculosis

This case report describes the presence of septic pulmonary embolism (SPE) in an older woman with diabetes whose initial manifestation was acute sepsis. She underwent computed tomography (CT) imaging, blood metagenomic next-generation sequencing (mNGS), and bronchoscopy, and was diagnosed with SPE secondary to Staphylococcus aureus-positive bacterial infection, combined with multidrug-resistant pulmonary tuberculosis and bronchial tuberculosis. In this case report, we focused on the clinical presentation and CT imaging features of SPE, and the application value of mNGS. This case study suggests that CT combined with mNGS has value in the timely diagnosis and management of SPE in patients with diabetes with severe pneumonia caused by mixed infection with multiple pathogenic pathogens.

Factors influencing histoplasmosis incidence in multidrug-resistant pulmonary tuberculosis patients: A cross-sectional study in Indonesia.

Histoplasmosis is an infectious disease caused by the dimorphic fungus Histoplasma capsulatum, which in chronic conditions, is generally difficult to distinguish from pulmonary tuberculosis (TB) based on its clinical appearance; therefore, diagnostic errors could occur. Meanwhile, the prevalence of multidrug-resistant pulmonary TB (MDR-TB) in Indonesia remains high. Study determining the incidence of histoplasmosis in MDR-TB is unavailable worldwide. The aim of this study was to determine the risk factors of histoplasmosis incidence in MDR-TB patients in Indonesia. A cross-sectional was conducted at H. Adam Malik General Hospital, Medan, Indonesia and the ELISA platform (semi-quantitative) was used to detect histoplasma antibodies. Factors associated with histoplasmosis incidence among MDR-TB were determined using a Chi-squared test. A total of 50 MDR-TB patients were included this study of which 14 of them (28%) had histoplasmosis. The majority of histoplasmosis occurred in males, in MDR-TB patients with a history of TB treatment and among who had chest x-rays with far-advanced lesions. However, statistical analyses indicated none of those factors (sex, TB treatment history, status of the lung) as well as age group, acid-fast bacillus result, Mycobacterium tuberculosis culture result, having pet, living in damp house, working in the field or plantation, having HIV infection and smoking status were associated with histoplasmosis incidence. This study highlights that the incidence of histoplasmosis is relatively high and therefore further studies are important to be conducted in Indonesia that has a high MDR-TB cases.

Low serum vitamin D in North Indian multi-drug resistant pulmonary tuberculosis patients: the role of diet and sunlight

Background: Tuberculosis (TB) and malnutrition are major global health problems, with multidrug-resistant (MDR) TB complicating international efforts. The role of vitamin D in susceptibility to and as an adjunctive treatment for TB is being studied extensively, although no study has included MDR-TB patients in context to dietary profile with vitamin D levels and sunlight exposure.Objective: This study aimed to estimate vitamin D serum levels and examine their association with dietary intake of vitamin D and sun exposure in patients with MDR-TB.Methods: North Indian participants were enrolled in three groups: MDR-TB, drug-susceptible pulmonary TB (DS-PTB), and healthy controls. All consenting participants underwent the estimation of macro- and micronutrient intake and sunlight exposure using structured questionnaires. Serum biochemistry, including 25-hydroxyvitamin D and calcium levels, was measured, and the correlation between variables was determined.Results: 747 participants were enrolled. Significant differences among the three groups were found in mean serum 25-hydroxyvitamin D levels, body mass index, macronutrient intake, dietary vitamin D and calcium content, and sun exposure index (SEI). All except sun exposure (SEI was highest in DS-PTB patients) were found to follow the trend: MDR-TB < DS-PTB < healthy controls. The mean serum vitamin D levels of all groups were deficient and correlated positively with dietary intake and SEI.Conclusion: In this study’s we found significant association of serum vitamin D concentrations, dietary intake and sunlight exposure in MDR-TB, DS-PTB patients and healthy controls. Dietary intake may be more important than sun exposure in determining serum levels. However, the significance of this finding is uncertain. Further studies are required to confirm the association, direction, and potential for vitamin D supplementation to treat or prevent MDR-TB infection.

Study on the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A

Objective: To summarize the resistance of rifampicin-resistant Mycobacterium tuberculosis to anti-tuberculosis drugs in group A. Methods: In the retrospective study, a total of 1 226 clinical isolates from suspected multidrug-resistant pulmonary tuberculosis patients in Beijing TB control system from 2016 to 2021 were identified as Mycobacterium tuberculosis (MTB) strains by MPB64 antigen detection test. Rifampicin-resistant tuberculosis (RR-TB) strains were screened by the phenotypic drug susceptibility using the proportion method. The drug susceptibilities of Levofloxacin(LFX), Moxifloxacin(MFX), Bedaquiline(BDQ) and Linezolid(LZD)were detected by the phenotypic drug susceptibility with microplate method. The drug resistance rate, drug resistance level and minimum inhibitory concentration (MIC) distribution of four anti-tuberculosis drugs in group A were analyzed. We calculated the demographic distribution of RR-TB, multidrug-resistant tuberculosis(MDR-TB), pre-extensively drug resistant tuberculosis (pre-XDR-TB), extensively drug resistant tuberculosis (XDR-TB) patients and the cross resistance of LFX and MFX, then summarized the drug-resistance spectrum of BDQ-resistant and LZD-resistant strains and the treatment outcome of RR-TB patients. Measurement data were expressed as rate or composition ratio,χ2 test was used between and within groups, and P<0.05 was considered statistically significant. Results: Among the 1 226 suspected multidrug-resistant pulmonary tuberculosis patients, the detection rates of RR/MDR/pre-XDR/XDR-TB patients were 20.8%(255/1 226), 15.2%(186/1 226), 5.7%(70/1 226), 0.5%(6/1 226), respectively. There were statistically significant differences in the distribution of patients with the four types of drug resistance in terms of age and treatment history (χ2=14.95, P=0.020;χ2=15.91, P=0.001). The drug resistance rates of LFX, MFX, BDQ and LZD in RR-TB patients were 27.5% (70/255), 27.5% (70/255), 0.4% (1/255) and 2.4% (6/255), respectively. The MICs of LFX, MFX and LZD-susceptible MTB were mainly at 0.25 mg/L, and the MIC of BDQ-susceptible MTB was mainly concentrated at 0.03 mg/L. 25.1% (64/255) of the RR MTB were resistant to both LFX and MFX, and 6 strains were resistant to LFX or MFX, showing incomplete two-way cross resistance. One BDQ-resistant strain and six LZD-resistant strains were detected. The treatment success rate of RR-TB patients was 74.4% (151/203), and there were statistically significant differences in treatment outcomes between resistant and sensitive patients on the LFX-containing treatment regimen (Fisher's exact test, P=0.012). Conclusions: The prevalence of fluoroquinolones (LFX and MFX) resistance in rifampicin-resistant MTB is very serious. LFX and MFX show incomplete bidirectional cross-resistance. BDQ and LZD have the most promising future in the treatment of MDR-TB. Improve drug-resistance testing will help to further improve the success rate of treatment.

Sirturo- a diarylquinoline (bedaquiline): a novel approach for the treatment of MDR-TB and pre-XDR TB

Sirturo (bedaquiline fumarate) is a new antitubercular class of medicine, lately, FDA, approved and indicated for use as a part of an appropriate applicable combination regimen along with other antitubercular medicines (i. e.; 2nd line anti-TB agents) for pulmonary multidrug-resistant tuberculosis (MDR TB) in grown up with age 12 years to less than 18 years of age and weighing at least 30 kg when an alternative treatment regimen cannot be considered for the reasons of resistance or tolerability. Bedaquiline, an enantiomer chemically belongs to the diarylquinoline (DAR) compound, which is nearly related to fluoroquinolones and chloroquine with differences in their side-chain moiety. Amongst all anti-TB medicines that have been approved, bedaquiline has a unique mechanism, which targets energy metabolism i. e.; adenosine triphosphate of mycobacteria, and eventually leads to bacterial cell lysis. ATP is an essential energy-producing molecule required for metabolic actions and survival of Mycobacteria and also for many other cells. Mycobacteria generally invade into well-encapsulated lung cavities and endosomes of macrophages, which can survive even under low oxygen levels leading to resistance against standard TB drugs. Bedaquiline has a spectrum of activity against drug-susceptible TB and MDR TB. Many clinical trials and studies demonstrated that bedaquiline is a crucial component of a combination regimen for multidrug-resistant TB.

Immunopathological response of the body in patients with chemosensitive and drug-resistant pulmonary tuberculosis

Immunological methods are important for diagnosing tuberculosis, evaluating the process activity, and forecasting the course of the disease and recovery.&#x0D; Materials and methods. 47 patients with first diagnosed destructive sputum smear-positive pulmonary tuberculosis underwent a complex immunoassay. The patients were divided into two groups based on the sensitivity/resistance of mycobacterium tuberculosis to antimycobacterial agents. The first group consisted of 22 patients with first-diagnosed chemosensitive tuberculosis with preserved sensitivity to antimycobacterial agents. The second group consisted of 25 patients with multi-drug resistant tuberculosis pulmonary tuberculosis (MDR-TBP). The research was conducted during the 2018-2021 years.&#x0D; Results Specific cell response disorders in patients with pulmonary tuberculosis are associated with the multi-structural T-cell protection misbalance caused by the quantitative changes of its components, the increase/decrease in the quantity of certain lymphocyte pools specifying the immune response vector.&#x0D; In cases of tuberculosis, phagocytosis plays an important role. Phagocytosis might release cells from the tuberculosis pathogen. To achieve this, the activation of cells should reach a certain level. However, the initial protective nature of cell activation might become aggressive.&#x0D; The T-cell immunity disorders were more evident in patients with MDR-TBP versus donors and patients with chemosensitive tuberculosis. The apparent decrease in СD3+СD56+, СD3+СD4+ pools and the increase in СD3+СD8+ were revealed in cases of MDR-TBP tuberculosis versus chemosensitive tuberculosis. The difference in СD3+СD4+, СD3+СD8+, СD3+СD4+/СD3+СD8+, CD3+СD8+HLA-DR+, СD16/56+8+ between the study and observational groups was statistically confirmed. The evident specific cell immunity disorders in patients with MDR-TBP aggravate the clinical course of the disease, causing destructive changes and acute and extensive processes.&#x0D; Conclusions Changes in different components of the immune system might occur during pulmonary tuberculosis (in T- and B-cells, phagocytic cells), specific and enzymatic processes are activated, and autoimmunization is evident. The intensity of the changes varies at different stages of the disease. Most immune disorders caused by the specific inflammation process require immune correction.

Prevalence And Risk Factors Of Multi Drug Resistant Tuberculosis In Children.

To assess the prevalence of drug-resistant tuberculosis and to identify possible risk factors in children. The descriptive, interview-based study was conducted at the Pulmonology outdoor clinic of Jinnah Hospital, Lahore, Pakistan, from January to August 2019, and comprised children aged up to 14 years who were either contacts of a multi-drug resistant tuberculosis patients or non-contacts. Data related to their demography as well as clinical and social characteristics was collected using a questionnaire. Data was analysed using SPSS version 22. Of the 202 subjects, 115(56.9%) were girls and 87(43.1%) were boys. There were 70(34.7%) subjects aged >13 years, followed by 45(22.3%) aged 9-12 years, 44(21.8%) aged £4 years and 43(21.3%) aged 5-8 years. Overall, there were 26(12.9%) cases positive for multi-drug resistant tuberculosis; 16(61.5%) girls and 10(38.5%) boys. In terms of age, 17(65.4) cases were positive in those aged >13 years. Age, previous history of tuberculosis, co- infection with any immune-compromising disease and close contact with patients of multi-drug resistant tuberculosis were significant risk factors identified. The prevalence of multi-drug resistant tuberculosis was high in contacts of multi-drug resistant pulmonary tuberculosis patients, more prevalent in children aged 13-14 years.

Mapping Research Trends of Medications for Multidrug-Resistant Pulmonary Tuberculosis Based on the Co-Occurrence of Specific Semantic Types in the MeSH Tree: A Bibliometric and Visualization-Based Analysis of PubMed Literature (1966-2020).

Before the COVID-19 pandemic, tuberculosis is the leading cause of death from a single infectious agent worldwide for the past 30 years. Progress in the control of tuberculosis has been undermined by the emergence of multidrug-resistant tuberculosis. The aim of the study is to reveal the trends of research on medications for multidrug-resistant pulmonary tuberculosis (MDR-PTB) through a novel method of bibliometrics that co-occurs specific semantic Medical Subject Headings (MeSH). PubMed was used to identify the original publications related to medications for MDR-PTB. An R package for text mining of PubMed, pubMR, was adopted to extract data and construct the co-occurrence matrix-specific semantic types. Biclustering analysis of high-frequency MeSH term co-occurrence matrix was performed by gCLUTO. Scientific knowledge maps were constructed by VOSviewer to create overlay visualization and density visualization. Burst detection was performed by CiteSpace to identify the future research hotspots. Two hundred and eight substances (chemical, drug, protein) and 147 diseases related to MDR-PTB were extracted to form a specific semantic co-occurrence matrix. MeSH terms with frequency greater than or equal to six were selected to construct high-frequency co-occurrence matrix (42 × 20) of specific semantic types contains 42 substances and 20 diseases. Biclustering analysis divided the medications for MDR-PTB into five clusters and reflected the characteristics of drug composition. The overlay map indicated the average age gradients of 42 high-frequency drugs. Fifteen top keywords and 37 top terms with the strongest citation bursts were detected. This study evaluated the literatures related to MDR-PTB drug therapy, providing a co-occurrence matrix model based on the specific semantic types and a new attempt for text knowledge mining. Compared with the macro knowledge structure or hot spot analysis, this method may have a wider scope of application and a more in-depth degree of analysis.

Development and validation of a prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance tuberculosis

BackgroundThe World Health Organization has reported that the treatment success rate of multi-drug resistance tuberculosis is approximately 57% globally. Although new drugs such as bedaquiline and linezolid is likely improve the treatment outcome, there are other factors associated with unsuccessful treatment outcome. The factors associated with unsuccessful treatment outcomes have been widely examined, but only a few studies have developed prediction models. We aimed to develop and validate a simple clinical prediction model for unsuccessful treatment outcomes in patients with multi-drug resistance pulmonary tuberculosis (MDR-PTB).MethodsThis retrospective cohort study was performed between January 2017 and December 2019 at a special hospital in Xi’an, China. A total of 446 patients with MDR-PTB were included. Least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were used to select prognostic factors for unsuccessful treatment outcomes. A nomogram was built based on four prognostic factors. Internal validation and leave-one-out cross-validation was used to assess the model.ResultsOf the 446 patients with MDR-PTB, 32.9% (147/446) cases had unsuccessful treatment outcomes, and 67.1% had successful outcomes. After LASSO regression and multivariate logistic analyses, no health education, advanced age, being male, and larger extent lung involvement were identified as prognostic factors. These four prognostic factors were used to build the prediction nomograms. The area under the curve of the model was 0.757 (95%CI 0.711 to 0.804), and the concordance index (C-index) was 0.75. For the bootstrap sampling validation, the corrected C-index was 0.747. In the leave-one-out cross-validation, the C-index was 0.765. The slope of the calibration curve was 0.968, which was approximately 1.0. This indicated that the model was accurate in predicting unsuccessful treatment outcomes.ConclusionsWe built a predictive model and established a nomogram for unsuccessful treatment outcomes of multi-drug resistance pulmonary tuberculosis based on baseline characteristics. This predictive model showed good performance and could be used as a tool by clinicians to predict who among their patients will have an unsuccessful treatment outcome.

Linezolid Pharmacokinetics and Its Association with Adverse Drug Reactions in Patients with Drug-Resistant Pulmonary Tuberculosis.

We evaluated the relationship between the pharmacokinetic parameters of linezolid (LZD) and development of adverse drug reactions (ADRs) in patients with pulmonary drug-resistant tuberculosis. A prospective cohort of adults with pulmonary multidrug-resistant tuberculosis with additional resistance to fluoroquinolone (MDR-TBFQ+) received treatment with bedaquiline, delamanid, clofazimine, and LZD. Blood samples were collected during weeks 8 and 16 at eight time points over 24 h. The pharmacokinetic parameters of LZD were measured using high-performance liquid chromatography and associated with ADRs. Of the 165 MDR-TBFQ+ patients on treatment, 78 patients developed LZD-associated anemia and 69 developed peripheral neuropathy. Twenty-three patients underwent intense pharmacokinetic testing. Plasma median trough concentration was 2.08 µg/mL and 3.41 µg/mL, (normal <2 µg/mL) and AUC0-24 was 184.5 µg/h/mL and 240.5 µg/h/mL at weeks 8 and 16, respectively, showing a linear relationship between duration of intake and plasma levels. Nineteen patients showed LZD-associated ADRs-nine at week 8, twelve at week 16, and two at both weeks 8 and 16. Thirteen of the nineteen had high plasma trough and peak concentrations of LZD. A strong association between LZD-associated ADRs and plasma LZD levels was noted. Trough concentration alone or combinations of trough with peak levels are potential targets for therapeutic drug monitoring.

Expert consensus on surgical treatment of multidrug-resistant and rifampicin-resistant pulmonary tuberculosis in China (2022 edition)

The cure rate of multidrug-resistant and rifampicin-resistant pulmonary tuberculosis in the world is about 60%, and timely surgical intervention can increase the cure rate to more than 85%. The treatment of multidrug-resistant and rifampicin-resistant pulmonary tuberculosis requires multidisciplinary involvement of tuberculosis department, thoracic surgery department, imaging department, laboratory department and other disciplines to significantly reduce its morbidity and mortality. Although the World Health Organization has defined the role and status of surgery in the treatment of multidrug-resistant and rifampicin-resistant pulmonary tuberculosis, there are significant differences in the cognition and diagnosis and treatment methods of domestic clinicians on multidrug-resistant and rifampicin-resistant pulmonary tuberculosis. Therefore, it is urgent to develop expert consensus on surgical treatment of multidrug-resistant and rifampicin-resistant pulmonary tuberculosis for clinicians to learn from in clinical diagnosis and treatment practice. The Chinese Society for Tuberculosis,Chinese Medical Association organized experts in tuberculosis thoracic surgery to write the first draft of consensus based on the expert suggestion on surgical diagnosis and treatment of multidrug-resistant pulmonary tuberculosis written by the European Office of the World Health Organization in 2014 and the 2019 version of China's multidrug-resistant and rifampicin-resistant pulmonary tuberculosis expert consensus, and combined with China's national situation. This consensus systematically elaborated seven aspects, including surgical indications, contraindications to surgery, conditions and timing of surgery, surgical methods and indications of various surgical procedures, preoperative and postoperative chemotherapy, treatment of surgical complications, and perioperative management of patients with multidrug-resistant and rifampin-resistant pulmonary tuberculosis. After discussion and voting by experts, six recommendations were formed, aiming to provide reference for clinicians in the treatment of multidrug-resistant and rifampin-resistant pulmonary tuberculosis and further improve the standardized diagnosis and treatment level of multidrug-resistant and rifampin-resistant pulmonary tuberculosis in China.

The Role of Omega-3/Omega-6 Ratio on Appetite in Pulmonary Multidrug-Resistant Tuberculosis Patients

Introduction: Tumour necrosis factor-alpha (TNF-α) levels, pro-inflammatory cytokines that suppress appetite, were discovered to be much higher in multidrug-resistant tuberculosis (MDR-TB) than in drug-sensitive TB. Research on the omega-3/omega-6 (ꞷ-3/ꞷ-6) polyunsaturated fatty acids (PUFAs) intake, which can support appetite in patients with MDR-TB, has never been performed. This study aimed to examine the relationship between ꞷ-3/ꞷ-6 PUFAs intake ratio and appetite mediated by TNF-α in pulmonary MDR-TB patients. Methods: This was a cross-sectional study conducted on 46 male and female adults with MDR-TB undergoing intensive phase therapy. Data were collected through questionnaires, 1x24 hours food recall, anthropometric measurements, 100 mm visual analogue appetite scale, and venous blood collection. Results: Correlation analysis used the Pearson and Spearman tests. The findings revealed the ratio of ꞷ-3/ꞷ-6 PUFAs intake of 0.11 ± 0.05, the median value of TNF-α 7.49(1.66-447.62) pg/mL, and an average appetite of 58.72 ± 26.7. There was no relationship between ꞷ-3/ꞷ-6 PUFAs intake ratio and TNF-α (r = 0.016; p = 0.91), likewise between ꞷ-3/ꞷ-6 PUFAs intake ratio with appetite (r = -0.1; p = 0.54), but there was a relationship between TNF-α and appetite (r = 0.031; p = 0.04). Conclusion: There was no relationship between ꞷ-3/ꞷ-6 PUFAs intake ratio and TNF-α and appetite in pulmonary MDR-TB patients. However, there was a relationship between TNF-α and appetite. This study is the first to determine the correlation between ꞷ-3/ꞷ-6 PUFAs intake ratio and appetite in pulmonary MDR-TB patients.