Multidrug-resistant Tuberculosis Patients Research Articles

Role of the IL8 rs4073 polymorphism in central nervous system toxicity in patients receiving multidrug-resistant tuberculosis treatment.

To determine the role of the IL8 rs4073 polymorphism in predicting the risk of central nervous system (CNS) toxicity in patients receiving standard pharmacological treatment for multidrug-resistant tuberculosis (MDR-TB). A cohort of 85 consenting MDR-TB patients receiving treatment with second-line antituberculosis drugs had their blood samples amplified for the IL8 (rs4073) gene and genotyped. All patients were clinically screened for evidence of treatment toxicity and categorized accordingly. Crude and adjusted associations were assessed. The chief complaints fell into the following categories: CNS toxicity; gastrointestinal toxicity; skin toxicity; and eye and ear toxicities. Symptoms of gastrointestinal toxicity were reported by 59% of the patients, and symptoms of CNS toxicity were reported by 42.7%. With regard to the genotypes of IL8 (rs4073), the following were identified: AA, in 64 of the study participants; AT, in 7; and TT, in 11. A significant association was found between the dominant model of inheritance and CNS toxicity for the crude model (p = 0.024; OR = 3.57; 95% CI, 1.18-10.76) and the adjusted model (p = 0.031; OR = 3.92; 95% CI, 1.13-13.58). The AT+TT genotype of IL8 (rs4073) showed a 3.92 times increased risk of CNS toxicity when compared with the AA genotype. The AT+TT genotype has a tendency to be associated with an increased risk of adverse clinical features during MDR-TB treatment.

Transmission of Fluoroquinolones Resistance among Multidrug-Resistant Tuberculosis in Shanghai, China: A Retrospective population-based Genomic Epidemiology Study

ABSTRACT Fluoroquinolones (FQ) are essential for the treatment of multidrug-resistant tuberculosis (MDR-TB). The FQ resistance (FQ-R) rate in MDR-TB in China and its risk factors remain poorly understood. We conducted a retrospective, population-based genomic epidemiology study of MDR-TB patients in Shanghai, China, from 2009 to 2018. A genomic cluster was defined as strains with genetic distances ≤ 12 single nucleotide polymorphisms. The transmitted FQ-R was defined as the same FQ resistance-conferring mutations shared by ≥ 2 strains in a genomic cluster. We used multivariable logistic regression analysis to identify the risk factors for drug resistance. Among the total 850 MDR-TB patients included in the study, 72.8% (619/850) were male, the median age was 39 (interquartile range 28, 55) years, 52.7% (448/850) were migrants, and 34.5% (293/850) were previously treated patients. Most of the MDR-TB strains belong to the Beijing lineage (91.7%, 779/850). Overall, the genotypic resistance rate of FQ was 34.7% (295/850), and 47.1% (139/295) FQ-R patients were in genomic clusters, of which 98 (33.2%, 98/295) were presumed as transmitted FQ-R. Patients with treatment-naïve (aOR = 1.84; 95% CI: 1.09, 3.16), diagnosed in a district-level hospital (aOR = 2.69; 95% CI: 1.56, 4.75), and streptomycin resistance (aOR = 3.69; 95% CI: 1.65, 9.42) were significantly associated with the transmission of FQ-R. In summary, the prevalence of FQ-R among MDR-TB patients was high in Shanghai, and at least one-third were transmitted. Enforced interventions including surveillance of FQ drug susceptibility testing and screening among MDR-TB before initiation of treatment were urgently needed.

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.

Adverse Drug Reactions in Multi-Drug Resistant Tuberculosis Patients, in India, who had received DOTS Plus Treatment along with Home Care and Counselling

Background: Adverse drug reactions are common in MDR-TB patients on treatment. An adverse drug reaction (ADR) is defined as an appreciably harmful or unpleasant reaction resulting from an intervention related to the use of a medicinal product. Revised National Tuberculosis Control Programme used 24-months long Category IV/DOTS Plus regimen for treatment of MDR-TB. The Community Health Department of St. Stephen’s Hospital started an innovative project in 2009, in the form of Home Care for MDR Patients and it concluded with Long-term Follow-up of patients, who had received DOTS Plus Treatment along with Home Care and Counselling (2015). Aims: To study the spectrum, severity and the risk factors for ADRs in MDR-TB patients. Methods: In this retrospective study files of 109 MDR-TB patients who had received treatment along with home care and counselling support, were reviewed. The study was conducted between January to May 2024. Results: Out of 109 MDR TB patients there were 68 (62%) developed one or more ADR. Joint pains 44(40.36%), was the most commonly observed ADR, followed by nausea 29(26.6%) and vomiting 25(22.93%), weakness 23(21.1%), anxiety and depression 16(14.67%), difficulty in breathing 14(12.84%), tremors 13(11.9%), giddiness 11(10.1%), skin rashes 10(9.2%). According to Hartwig Scale mild ADRs were 58.8%, moderate 5.9% and severe 35.3%. Patients who had BMI &lt;18.5 experienced less ADRs with an Odds Ratio =0.22; 95% CI=0.06 to 0.72, p=0.0124. Unemployment was associated with higher number of ADRs OR=3.5; 95% CI=0.99 to 12.29, p=0.05. Sixty-two % MDR TB patients had ADRs. Our treatment outcomes showed 41(60.3) as cured, 24(35.3) died, 2(2.9) defaulted and 1(1.5) failed treatment. This was possible because healthcare teams counselled and provided all possible support to patients 24x7 thus improving adherence to therapy. Conclusion: ADRs occurred in more than half of the cases, with joint pain being the most common. Interventions such as counselling of patients and their family on importance of adherence to drugs at the initiation of treatment, provision of nutritional support, psychological counselling and motivation, instant referral for ADRs and care of patients at referred facilities, help patients not becoming defaulters.

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.

Identification of urine biomarkers predictive of prolonged QTc interval in multidrug-resistant tuberculosis patients treated with bedaquiline.

The most frequent adverse event associated with bedaquiline (BDQ) is the QTc interval prolongation; however, there was no biomarkers that could be used to predict the occurrence of QTc prolongation in BDQ-treated patients. In this study, we employed the ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) to generate metabolic profiling for the discovery of potential predictive urine biomarkers of QTc prolongation in these patients. Untargeted metabolomic technique was used to concentrate the differential metabolic pathway, and targeted metabolomic technique was subsequently performed to identify predictive biomarkers for QTc prolongation. A total of 45 rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB) patients were enrolled in our study, including 15 RR/MDR-TB patients with QTc interval prolongation (QIP) and 30 RR/MDR-TB patients with QTc interval un-prolongations (QIU). Untargeted technique revealed that the lipid metabolism was the most differential metabolic pathway between two groups. Further targeted technique identified four differential metabolites, including betaine, LPE (18:2), LPE (20:3), and LPE (20:4). The combined analysis of metabolisms revealed that the combined use of LPE (20:3) and LPE (20:4) had the best performance for predicting the occurrence of QTc prolongation in TB patients, yielding a sensitivity of 87.4% and a specificity of 78.5%. In addition, with the progression of BDQ treatment, the LPEs exhibited persistent difference in the BDQ-treated TB patients experiencing QTc interval prolongation. In conclusion, our data demonstrate that the combined use of LPE (20:3) and LPE (20:4) yields promising performance for predicting the occurrence of QTc interval prolongation in BDQ-treated patients.

Recent advances in drug therapy for tuberculosis

Despite global efforts to control and eradicate tuberculosis (TB), it remains a significant source of morbidity and mortality worldwide. Drug-resistant TB (DRTB) is a significant public health threat with implications for global health security, economic burden, and access to quality care. To address this challenge, continued investment in research, surveillance, and innovative strategies is crucial. Collaboration among international organizations, governments, and health-care systems is crucial to tackle this global health concern effectively. Bedaquiline (BDQ), a diarylquinoline drug, is indicated for combination therapy in adult patients with pulmonary multidrug-resistant TB (MDRTB). The Food and Drug Administration (FDA) granted accelerated approval in December 2012, based on analysis of time to sputum culture conversion from two phase 2 trials. The World Health Organization (WHO) published interim policy guidance for BDQ in conjunction with WHO-recommended MDRTB treatments in June 2013. The European Medicines Agency authorized Delamanid as a first-in-class bicyclic nitroimidazole for treating MDRTB, which has been used in 89 and 54 nations due to its quick acquisition of resistance. To prevent resistance, combined therapy with additional anti-TB drugs is advised, along with proper use and drug resistance monitoring. Pretomanid received approval from the US FDA in August 2019 after a phase III trial yielded encouraging results. The bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) regimen, a component of the BPaLM regimen, has been approved for treating adults with extensive pulmonary DRTB or treatment-intolerant or non-responsive MDRTB. This significant advancement in management offers improved clinical outcomes and quality of life for MDRTB patients. The inclusion in the WHO guidelines is encouraging for global combat against DRTB. Researchers have identified and investigated new drug targets within the TB pathogenesis, offering promising avenues for the development of innovative anti-TB drugs. Advances in pediatric TB treatment have made significant progress, focusing on improved diagnostic methods, effective drug treatments, and global initiatives. Nanotechnology has shown promising potential in various fields, including medicine and TB treatment.

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.

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.

Evaluation of the Efficacy and Safety of Linezolid by Meta-analysis for Multidrug-resistant Tuberculosis Patients

Evaluation of the Efficacy and Safety of Linezolid by Meta-analysis for Multidrug-resistant Tuberculosis Patients

Impact of Education on Non-Compliance and MDR TB Risk: Specialized Hospital Study

Background: Multidrug-resistant tuberculosis (MDR-TB) poses a significant global health threat, with treatment challenges linked to patient non-compliance. Education has been proposed as a potential strategy to improve adherence and reduce the risk of MDR-TB. This study aims to assess the impact of education on non-compliance and MDR-TB risk among patients receiving treatment at a specialized hospital. Objective: The primary objective of this retrospective cross-sectional study was to determine whether education provided to MDR-TB patients could reduce non-compliance rates and subsequently mitigate the risk of MDR-TB. Methods: The study included 50 MDR-TB patients who had received at least three months of treatment. Data were collected from the MDR-TB wards at the National Institute of Disease of the Chest and Hospital in Dhaka, spanning from October 2011 to March 2012. Patient education interventions focused on treatment adherence and MDR-TB prevention. Results: The study's findings demonstrate a substantial decrease in non-compliance rates Among MDR-TB patients, 64% had a history of non-compliance, with 72% being male and primarily having lower educational backgrounds. Conversely, 70% of drug-compliant patients had attained at least a secondary education level. Educational interventions led to a significant 20% reduction in non-compliance, from an initial 28% to a final 8%, emphasizing their potential to reduce MDR-TB risk. Conclusion: This study demonstrates the positive impact of education on reducing non-compliance among MDR-TB patients. A 20% reduction in non-compliance rates indicates that educational interventions can effectively contribute to decreasing the risk of MDR-TB. Future efforts should prioritize integrating education into MDR-TB treatment programs to enhance patient adherence and reduce the burden of MDR-TB.

Economic Burden of Tuberculosis for Patients and their Households in Cochabamba, Bolivia

Background: Patients with tuberculosis usually incur large costs directly related to their disease. Additional indirect costs also increase the economic burden of households creating barriers of access and adherence. Because TB affects the poorest segment of society the effects can be more serious for poor people. Indirect costs are poorly documented in Bolivia. We therefore conducted a study to determine the socioeconomic impact of TB on patients and their households.&#x0D; Methods: A cross-sectional survey was carried out on 2017 in Cochabamba, Bolivia, included all patients who were on TB treatment within the health network. The generic survey instrument proposed by WHO for tuberculosis patients cost surveys was used. The most important direct medical and direct non-medical payments were calculated in a disaggregated manner. The calculation of indirect costs was carried out through the results-based approach where the loss of income was calculated from the report of household income. Catastrophic cost was determined and multivariable logistic regression was run to assess which factors were independently associated.&#x0D; Results: The indirect costs during an entire illness episode had a median of USD 768.1 corresponding to 63.4% of the total cost for all patients. In the case of multidrug-resistant TB (MDR TB) patients, the median cost was USD 6454.8 corresponding to 54.3% of their total costs. Direct non-medical costs had a median for all patients of USD 408.7 (33.7%), and of USD 5399.6 (45.4%) for MDR TB patients. The most important non-medical costs were those linked to directly observed treatment (DOT) with a median of USD 419.8 during intensive phase and of USD 108.6 during continuation phase for transport costs. Food and drinks costs had a median of USD 94.5 during intensive phase and of USD 54.8 during continuation phase; consumption of nutritional supplements had a median cost of USD 249.1 and additional food outside the regular diet had a median cost of USD 519 for all patients. Catastrophic costs were incurred by 43.9% of TB patients. These catastrophic costs were observed in 50% of the population aged over 55 years, in 60% of MDR-TB patients, and in 63% of poor patients. Using logistic regression, factors associated with a higher risk of catastrophic costs were to live in an urban province (OR = 1.82 1.11 to 2.98, P = 0.002), to be older than 55 years (OR = 1.21 1.07 to 1.38, P = 0.005), and to have a low economic income (OR = 0.83 0.69 to 0.99, P = 0.049).&#x0D; Conclusions: Patients with TB treated in health services face a great financial burden. Indirect cost was higher than direct costs in a complete TB episode, especially in MDR-TB patients. During the treatment, the most important costs were those related to transport and food when patients went to DOT; nutritional supplements and additional food to the regular diet accounted also for a non-negligible cost. Almost half of patients suffer a catastrophic cost, especially those who came from an urban province, those who were older than 55 years, and those having a low economic income.&#x0D; &#x0D;

Economic burden of multidrug-resistant tuberculosis on patients and households: a global systematic review and meta-analysis

Multidrug-resistant tuberculosis (MDR-TB) is a major health threat worldwide, causing a significant economic burden to patients and their families. Due to the longer duration of treatment and expensive second-line medicine, the economic burden of MDR-TB is assumed to be higher than drug-susceptible TB. However, the costs associated with MDR-TB are yet to be comprehensively quantified. We conducted this systematic review and meta-analysis to determine the global burden of catastrophic costs associated with MDR-TB on patients and their households. We systematically searched five databases (CINHAL, MEDLINE, Embase, Scopus, and Web of Science) from inception to 2 September 2022 for studies reporting catastrophic costs on patients and affected families of MDR-TB. The primary outcome of our study was the proportion of patients and households with catastrophic costs. Costs were considered catastrophic when a patient spends 20% or more of their annual household income on their MDR-TB diagnosis and care. The pooled proportion of catastrophic cost was determined using a random-effects meta-analysis. Publication bias was assessed using visualization of the funnel plots and the Egger regression test. Heterogeneity was assessed using I2, and sub-group analysis was conducted using study covariates as stratification variables. Finally, we used the Preferred Reporting Items for Reporting Systematic Review and Meta-Analysis-20 (PRISMA-20). The research protocol was registered in PROSPERO (CRD42021250909). Our search identified 6635 studies, of which 11 were included after the screening. MDR-TB patients incurred total costs ranging from $USD 650 to $USD 8266 during treatment. The mean direct cost and indirect cost incurred by MDR-TB patients were $USD 1936.25 (SD ± $USD 1897.03) and $USD 1200.35 (SD ± $USD 489.76), respectively. The overall burden of catastrophic cost among MDR-TB patients and households was 81.58% (95% Confidence Interval (CI) 74.13–89.04%). The catastrophic costs incurred by MDR-TB patients were significantly higher than previously reported for DS-TB patients. MDR-TB patients incurred more expenditure for direct costs than indirect costs. Social protection and financial support for patients and affected families are needed to mitigate the catastrophic economic consequences of MDR-TB.

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.

The trial of sending short message service multidrug-resistant tuberculosis patients in Indonesia: the chance to increase knowledge and motivation.

Multidrug-Resistant Tuberculosis (MDR TB) is a threat for the future control of TB disease. In Indonesia, the success rate of MDR TB patient recovery is still very low, following the still low recovery rate of TB patients. This paper aims to discuss the trial result of message delivery containing knowledge and motivation to the MDR TB sufferers. There are about 34 MDR TB patients participating in this research. During the research, everyone received a message in their handphone or the handphone of their family members every day, contained information on medication and motivation to comply with the medication. At the end of the research, the measurement on knowledge and attitude, on the compliance with medication, and on the compliance with laboratory examinations was conducted. The results were compared with the assessment before this intervention was conducted. Out of 32 patients that managed to complete the intervention, the average means of their knowledge and attitude increased significantly. The average mean of knowledge before the intervention was 9.74 to become 10.94, and the average mean of attitude was from 7.06 to become 18.47 (P<0.05). Meanwhile, the medication compliance score and the laboratory examination compliance score also changed significantly (P<0.05). SMS delivery routinely even in a short period of time managed to change knowledge and motivation of MDR TB sufferers. To conclude, it is necessary to develop recent technology effort in order to scaling-up MDR TB patients. Existing social channels in the community must be used intensively to reduce this disease negative impact.

Study on the relationship between Vitamin D deficiency and Leukocyte Ratio in Multidrug Resistant Tuberculosis patients

Tuberculosis (TB) remains an important health problem in Indonesia,the problems more complex with phenomenon of multi-drug resistance Tuberculosis (MDR) which cause worse prognosis, long treatment,high risk of transmission to other and side effect of treatment. Vitamin D plays a role in non specific and specific immune responses in Mycobacterium tuberculosis (M.tb) infection. Vitamin D have a role in hematopoiesis and affects the early development of monocytes and granulocytes. M.tb infection causes changer in the ratio of neutrophil cells, lymphocytes and monocytes. Changes in the ratio reflect an increase or decrease of effective immune response. Using a case control design, this study will evaluate the correlation between vitamin D, leukocyte ratio and MDR-TB patients among MDR-TB patient cases and TB patient controls. Independent variable in this study were vitamin D levels, leukocyte ratios consisting of NLR, MLR, NMLR, and clinical status of respondents were the dependent variable. The result of this study found that vitamin D levels of TB patients all showed values ​​that were within range of in the insufficiency and deficiency categories. From this result TB patients must coverIn addition, the NLR and NMLR parameters were able to show that immune status problems were mainly found in the MDR-TB patients

Efektivitas dan keamanan terapi dengan rejimen yang mengandung linezolid dalam pengobatan multidrug-resistant tuberculosis (MDR-TB): Kajian Sistematik

Objective: To systematically evaluate the existing evidence regarding the efficacy and safety of therapy with regimens containing linezolid in the treatment of Multidrug‐ resistant tuberculosis (MDR-TB). Data source: The search strategy was undertaken using PubMed, Cochrane, and ScienceDirect databases. Review method: Searching the literature without changing the type of research or year of publication in which articles published until March 14, 2021, are involved in this literature review. The search strategy undertaken using PubMed, Cochrane, and ScienceDirect with the keywords "linezolid", "treatment", "tuberculosis" and "multidrugresistant" which were combined with the use of a Boolean operator "AND". Results: A total of seven studies were included in the final study. Linezolid had efficacy in MDR-TB patients with a much higher level of treatment support in the linezolid therapy group than in the control group (not using linezolid). However, the side effects that occurred were categorized as hematologic, gastrointestinal, neurological, and dermatological which generally occurred after 278 days of use. Severe diarrhea and nausea shortly after starting treatment were felt in 12.5% of patients. The main side effects controlled with linezolid (anemia, thrombocytopenia, and/or polyneuropathy), which generally required discontinuation were reported in 1 study and required discontinuation in 27 (77%) cases. The most important side effect is peripheral neuropathy, necessary to monitor the report by the 5 articles included in the final study. Conclusion: Available evidence has shown linezolid therapy to be effective against MDR-TB treatment. Monitored for the incidence of major adverse neurotoxicity (peripheral or optic neuropathy). To follow side effects and improve clinical outcomes, a combined high dose (1200 mg daily) for the intensive phase followed by a lower dose (300-600 mg daily) for the continuous phase is recommended along with an effective patient to increase the current dose and monitoring.

ARTICLE REVIEW: THE TREATMENT PROBLEM AND ADVERSE DRUG REACTIONS IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS

Multidrug-resistant tuberculosis (MDR-TB) is the resistance of Mycobacterium tuberculosis to at least two tuberculosis (TB) drugs, rifampicin and isoniazid. The disease requires a long treatment duration with several second-line drugs. This leads to a globally low success rate of approximately 56% for MDR-TB treatment. Studies have reported that adverse drug reactions (ADRs) contribute to high rates of non-compliance, treatment discontinuation, and failure. This narrative review aimed to provide information about MDR-TB treatment modalities, various ADRs, challenges encountered in MDR-TB treatment, and instances of ADRs that can impact treatment success. This narrative review study was conducted by searching for scientific information from the primary electronic databases PubMed and Google Scholar, covering 2012-2022. Based on the literature search results, 14 studies were identified, demonstrating challenges in TB and MDR-TB treatment, along with 6 ADRs that can influence treatment success in MDR-TB patients. ADRs during MDR-TB treatment can affect patients’ physical, mental, and social well-being as well as their beliefs and behaviors related to treatment. Comprehensive support from families, communities, and healthcare providers is essential to assist patients in addressing treatment challenges and adverse ADRs. Rapid identification and strategies for monitoring and managing treatment challenges and ADRs can improve compliance and success of MDR-TB treatment. Keywords: Adverse Drug Reactions, Drug Side Effects, Multi Drug-Resistant Tuberculosis (MDR-TB), Treatment Success

Influencing factors of death in patients with MDR-TB based on Bayesian Cox regression model.

Multidrug-resistant tuberculosis (MDR-TB) has a high mortality and is always one of the major challenges in global TB prevention and control. Analyzing the factors that may impact the adverse outcomes of MDR-TB patients is helpful for improving the systematic management and optimizing the treatment strategies for MDR-TB patients. For follow-up data, the Cox proportional hazards regression model is an important multifactor analysis method. However, the method has significant limitations in its application, such as the fact that it is difficult to deal with the impacts of small sample sizes and other practical issues on the model. Therefore, Bayesian and conventional Cox regression models were both used in this study to analyze the influencing factors of death in MDR-TB patients during the anti-TB therapy, and compare the differences between these 2 methods in their application. Data were obtained from 388 MDR-TB patients treated at Lanzhou Pulmonary Hospital from November 1, 2017 to March 31, 2021. Survival analysis was employed to analyze the death of MDR-TB patients during the therapy and its influencing factors. Conventional and Bayesian Cox regression models were established to estimate the hazard ratios (HR) and their 95% confidence interval (95% CI) for the factors affecting the death of MDR-TB patients. The reliability of parameter estimation in these 2 models was assessed by comparing the parameter standard deviation and 95% CI of each variable. The smaller parameter standard deviation and narrower 95% CI range indicated the more reliable parameter estimation. The median survival time (1st quartile, 3rd quartile) of the 388 MDR-TB patients included in the study was 10.18 (4.26, 18.13) months, with the longest survival time of 31.90 months. Among these patients, a total of 12 individuals died of MDR-TB and the mortality was 3.1%. The median survival time (1st quartile, 3rd quartile) for the deceased patients was 4.78(2.63, 6.93) months. The majority of deceased patients, accounting for 50%, experienced death within the first 5 months of anti-TB therapy, with the last mortality case occurring within the 13th month of therapy. The results of the conventional Cox regression model showed that the risk of death in MDR-TB patients with comorbidities was approximately 6.96 times higher than that of patients without complications (HR=6.96, 95% CI 2.00 to 24.24, P=0.002) and patients who received regular follow-up had a decrease in the risk of death by approximately 81% compared to those who did not receive regular follow-up (HR=0.19, 95% CI 0.05 to 0.77, P=0.020). In the results of Bayesian Cox regression model, the iterative history plot and Blue/Green/Red (BGR) plot for each parameter showed the good model convergence, and parameter estimation indicated that the risk of death in patients with a positive first sputum culture was lower than that of patients with a negative first sputum culture (HR=0.33, 95% CI 0.08 to 0.87). Additionally, compared to patients without complications, those with comorbidities had an approximately 6.80-fold increase in the risk of death (HR=7.80, 95% CI 1.90 to 21.91). Patients who received regular follow-up had a 90% reduction in the risk of death compared to those who did not receive regular follow-up (HR=0.10, 95% CI 0.01 to 0.30). The comparison between these 2 models showed that the parameter standard deviations and corresponding 95% CI ranges of other variables in the Bayesian Cox model were significantly smaller than those in the conventional model, except for parameter standard deviations of receiving regular follow-up (Bayesian model was 0.77; conventional model was 0.72) and pulmonary cavities (Bayesian model was 0.73; conventional model was 0.73). The first year of anti-TB therapy is a high-risk period for mortality in MDR-TB patients. Complications are the main risk factors of death in MDR-TB patients, while patients who received regular follow-up and had positive first sputum culture presented a lower risk of death. For data with a small sample size and low incidence of outcome, the Bayesian Cox regression model provides more reliable parameter estimation than the conventional Cox model.

Assessment of Comorbidity in Patients with Drug-Resistant Tuberculosis.

A wide range of comorbidities, especially in multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) patients, markedly complicates selecting effective treatment of tuberculosis (TB) and preventing the development of adverse events. At present, it is impossible to assess the severity of comorbid pathologies and develop indications for the administration of accompanying therapy in TB patients. The aim of this study was to identify the difference in the range of comorbidities between patients with MDR-TB and XDR-TB and assess the impact of comorbidities on TB treatment. Materials and Methods: A retrospective, prospective study was conducted where 307 patients with MDR-TB and XDR-TB pulmonary tuberculosis aged 18 to 75 years who received eTB treatment from 2016 to 2021 in St. Petersburg hospitals were analyzed. The analysis showed that the comorbidity level in MDR-TB and XDR-TB patients with TB treatment success and treatment failure was comparable with the use of the Charlson Comorbidity Index (CCI). The CCI demonstrated declining data in terms of TB treatment outcome period in both groups. A slight predominance of CCI score (3 to 4 points) in XDR-TB (22.7%) vs. MDR-TB (15.4%) patients was found. In the case of an TB treatment failure, the CCI level in MDR-TB vs. XDR-TB patients was characterized by a significantly higher rate of low magnitude (ranging from 1 to 2 points) in 21.1% vs. 4.5% (p < 0.05), which was higher in XDR-TB patients (ranging from 4 to 5 points, in 10.0% vs. 0, χ2 = 33.7 (p < 0.01)). Chronic viral hepatitis B and C infection, cardiovascular pathology, chronic obstructive pulmonary disease, and chronic alcoholism were found to be significant comorbidity factors that influenced the TB treatment success. Conclusions: It is evident that XDR-TB patients comprise a cohort with the most severe disease course due to comorbidities impacting TB treatment efficacy. The obtained data pointed to the need to determine comorbidity severity in patients with drug-resistant Mbt prior to administering TB treatment schemes.