MDR-TB Treatment Research Articles

Treatment success using novel and adapted treatment regimens in registered DR-TB children in Dushanbe, Tajikistan, 2013-2019.

Approximately 3% of all pediatric TB cases develop MDR-TB, with only 3-4% of such children receiving MDR-TB treatment. In Tajikistan, children as a proportion of all DR-TB in the country increased from 4.3 to 7.5% during 2013-2018. Despite limited evidence on the use of new anti-TB drugs in children, WHO has updated its guidelines for DR-TB treatment for children, and Tajikistan did so in 2013 and 2017. Novel and adapted regimens included individual regimens for RR/MDR, XDR (with and without Bedaquiline and Delamanid) and short treatment regimens with and without injectables. It is important to document the outcomes of the treatment regimens. Therefore, the aim of this study was to describe characteristics of children receiving different treatment regimens for DR-TB, the culture conversion and treatment outcomes. Cohort study of children enrolled in DR-TB treatment by the National Tuberculosis Program in Dushanbe, Tajikistan, January 2013 to July 2019. The study included 60 DR-TB children. The male to female ratio was 1:2 and mean age 13.6 years. Median time to culture conversion was 66 days [IQR:31-103; Range:2-232]. In children with treatment outcomes (N = 58), 93% had favorable outcomes. There were four children (7%) with unfavorable treatment outcomes, all of whom were female 15-17 years, on standard (RR/MDR) treatment during 2013-2015. Favorable outcomes by DR-TB type were 91%, 90%, and 100% in RR/MDR, PreXDR, and XDR-TB patients, respectively. All children enrolled after the introduction of modified guidelines for novel and adapted regimens for DR-TB showed positive TB treatment outcomes.

The Use of Molecular Genetic Diagnostic Tests to Improve MDR TB Treatment Outcomes in Arkhangelsk Region

The use of molecular genetic tests as a part of tuberculosis patients examination made it possible to reduce the time for TB diagnosis and determination of drug resistance (DR) of M. tuberculosis (MTB) in Arkhangelsk Region. Early detection of multiple drug resistant tuberculosis (MDR TB) made it possible to prescribe the adequate chemotherapy regimen promptly and thus to improve treatment outcomes.The objective of the study: to evaluate the results of treatment of MDR TB patients in whom MDR TB was diagnosed by molecular genetic tests. It was assumed that the introduction of molecular genetic tests would result in improved treatment outcomes in MDR TB patients [(the research project of the International Union Against Tuberculosis and Lung Diseases and Tuberculosis Control Program of Arkhangelsk Region of the PROVE-IT LPA (Policy Relevant Outcomes from Validating Evidence on Impact of Line Probe Assays)].Subjects: 295 MDR TB patients detected in Arkhangelsk Region were enrolled in the study. MDR TB was detected by molecular genetic tests in the main group (132 patients) and by culture in the control group (163 patients). Patients from both groups received the standard chemotherapy regimen. Chemotherapy outcomes were compared in both groups.Results. Treatment outcomes were better in the group (MGT group) where molecular genetic tests were used for drug susceptibility testing (p = 0.003) versus the comparison group where the culture was used. Effective treatment was documented more frequently (65.2%) in the MGT group versus the comparison group (44.8%). All-cause mortality was lower in the MGT group (7.6%) than in the comparison group (15.9%). There were no statistically significant differences between the groups in the time when sputum conversion (by smear and culture) was achieved.

WULIRA APP mobile phone application to assess occupational hearing loss among industrial workers in Kampala, Uganda

BACKGROUND AND AIM: Occupational hearing loss (OHL) is among the most common causes of disabling hearing loss. Pure Tone Audiometry (PTA) is not readily available in Uganda due to the high cost and operator dependence. However, a mobile phone-health innovation, Wulira App, with a sensitivity of 91.4% in the right ear and 88.4% in the left ear and a specificity of 93.2% and 91.5% in the right and left ear respectively, provides an easy to use, and reliable alternative screening tool for hearing loss. In this study, the prevalence and associated factors of OHL among industrial workers will be determined. METHODS: We will conduct a cross-sectional study among industrial workers in Kampala. A total of 354 participants will be recruited systematically and screened for hearing loss using the Wulira App in a quiet room. Noise cancelling earphones will be used to minimize interference from any ambient noises. The study population will be described by exposure variables such as duration of work in the factory, age, sex, smoking, previous MDR-TB treatment. Categorical data will be presented as frequencies and percentages while continuous variables will be presented as means and standard deviations or medians and interquartile ranges. Proportions for categorical variables will be compared using the chi-square tests and Fisher’s exact tests after testing for assumptions whereas means of continuous variables will be compared using Student t-test for normally distributed data and Mann Whitney U test for skewed data. Inferential statistics will be used. RESULTS:Using a hearing threshold more than or equal to 26 dB as hearing loss, participants with OHL will be presented as proportions and classified according to the WHO classification of hearing loss. CONCLUSIONS:Wulira App is easy to use tool for assessing OHL. Therefore, Wulira App could be adopted in clinical and work settings to screen and monitor for hearing loss. KEYWORDS: Occupational exposure, Occupational epidemiology

Early detection of MDR Mycobacterium tuberculosis mutations in Pakistan

The result of improper treatment has led to the rise of Multidrug-resistant (MDR) strains. This concern still exists in Pakistan. In order to save energy, time and resources an early detection of resistant cases is imperative. Thus, a treated group of 100 isolates and a control group of 56 untreated isolates were studied. PCR and gene sequencing showed mutations at codon 531 and 513 in the rpoB gene. 12% of cases showed a double mutation in the rpoB gene. katG gene showed mutations at codon 315 and 299. 28.6% of the control group cases were positive for MDR whereas 100% of the treated group were positive for MDR. This study explores the significantly increasing ratio of MDR-TB among Pakistani population. This study provides prevalent MDR mutations among Pakistanis and suggests developing such molecular assays that are time and cost effective. Importance: Pakistan is a developing country and has fourth highest incidence rate of MDR-TB. The treatment of MDR-TB is the use of second line drugs that has severe side effects as well as it requires long time span. One of the strategies to control the spread of MDR-TB is to decipher the aberrations at molecular level in order to formulate potent drugs that can treat the patients within short span of time. Determining the mutation profile of MDR in Pakistani populations will open new horizons for the improvement of drug treatment regimens to make it more effective or for the development of novel potent drugs and vaccines to better treat the drug-resistant TB. Moreover, this study will be help in disease control program.

Pharmacoepidemiology and pharmacoeconomics of multidrug- and extensively drug-resistant tuberculosis

Treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) is a current problem worldwide. Currently, special attention is paid to the possibility of using new high-cost chemotherapy regimens in the treatment of MDR/XDR-TB. Numerous studies have shown that, from a clinical point of view, the effectiveness of MDR/XDR-TB therapy increases with the inclusion of bedaquiline, delamanid, linezolid, fluoroquinolones (moxifloxacin, levofloxacin), and pretomanid. At the same time, there is an assumption that the use of new and repurposed anti-tuberculosis drugs (ATDs) may be associated with an increase in overall costs. This paper demonstrates the potential of pharmacoepidemiology and pharmacoeconomics to evaluate the widespread introduction of new anti-tuberculosis drugs (ATDs), taking into account all the typical features of MDR/XDR-TB therapy. The authors analyzed studies of pharmacoeconomic feasibility of using expensive drugs in treatment regimens of pulmonary tuberculosis patients with MDR/XDR pathogen. It was shown that the use of chemotherapy regimens containing new high-cost and highly effective drugs (moxifloxacin, linizolid, and bedaquiline) in rational combinations with other drugs of the basic and reserve series, selected concerning drug resistance of the pathogen, is associated with a significant economic effect. From the applicability of pharmacoeconomic analysis point of view, the introduction of short-term MDR-TB treatment regimens is also a promising direction in phthisiology. The key link to achieve effective MDR/XDR-TB treatment is the use of new drugs. Considering the specificity of pharmacoeconomic analysis in phthisiology and results of existing clinical and economic studies, the authors have formed recommendations aimed at a more complete realization of pharmacoeconomic analysis potential in MDR- and XDR-TB treatment.

Measuring Catastrophic Costs Due to Tuberculosis in Myanmar.

Background: This is the first survey to use the World Health Organization (WHO) methodology to document the magnitude and main drivers of tuberculosis (TB) patient costs in order to guide policies on cost mitigation and to produce a baseline measure for the percentage of TB-affected households experiencing catastrophic costs in Myanmar. Methods: A nationally representative cross-sectional survey was administered to 1000 TB patients in health facilities from December 2015 to February 2016, focusing on costs of TB treatment (direct and indirect), household income, and coping strategies. A total cost was estimated for each household by extrapolating reported costs and comparing them to household income. If the proportion of total costs exceeded 20% of the annual household income, a TB-affected household was deemed to have faced catastrophic costs. Results: 60% of TB-affected households faced catastrophic costs in Myanmar. On average, total costs were USD 759, and the largest proportion of this total was accounted for by patient time (USD 365), followed by food costs (USD 200), and medical expenses (USD 130). Low household wealth quintile and undergoing MDR-TB treatment were both significant predictors for households facing catastrophic costs. Conclusions: The high proportion of TB-affected households experiencing catastrophic costs suggests the need for TB-specific social protection programs in patient-centered healthcare. The survey findings have led the government and donors to increase support for MDR-TB patients. The significant proportion of total spending attributable to lost income and food or nutritional supplements suggests that income replacement programs and/or food packages may ameliorate the burdensome costs.

Patient treatment pathways of multidrug-resistant tuberculosis cases in coastal South India: Road to a drug resistant tuberculosis center

Background: Delays in initiating multidrug-resistant tuberculosis (MDR TB) treatment adds risk to individual patients and the community due to disease progression, and on-going transmission. The Government of India offers free TB diagnosis and treatment, however many presumptive MDR TB patients wander within the Indian healthcare system and delay accessing the programme. To improve access to care, it is imperative to understand the treatment pathways taken by MDR TB patients. We aimed to describe the diagnostic and treatment pathway taken by presumptive MDR TB patients registered under Programmatic Management of Drug-resistant TB Program. Methods: We conducted a cross-sectional study amongst patients registered during August 2016 – April 2017 at one District Drug Resistance Tuberculosis centre of Dakshina Kannada district in Karnataka, India. A semi-structured questionnaire was used to collect the number, type (private and public sector), and dates of healthcare facilities (HCFs) visits prior to the initiation of MDR TB treatment. Delays in pathway were measured in days and summarised as median and interquartile range (IQR), from the date of onset of illness until the initiation of MDR TB treatment. Results: We found that patients preferred private HCFs; however, due to lack of treatment and unaffordability they shifted to public HCFs. Median delay to register under the program was more in private HCFs (180 days) in comparison with public HCFs (120 days). We also found that the detection rates were much higher in public HCFs (80%). Conclusion: The present study found that there was substantial patient delay and total delay in diagnosis and treatment of MDR TB patients. Private HCF was first point of contact for most of the patients; however those visited public HCF diagnosed earlier as compared to others. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

Thyroid Profile and Factors Associated with Hypothyroidism Among Multidrug-Resistant Tuberculosis Patients Attending Saint Peter's Specialized Hospital Addis Ababa, Ethiopia.

BackgroundThe emergence of MDR-TB is a global public health problem. Hypothyroidism is one of the severe adverse drug reactions (ADRs) in MDR-TB patients on treatment. Representative data on hypothyroidism and its associated factors among MDR-TB patients are lacking.ObjectiveTo determine thyroid profiles and associated risk factors among multidrug-resistant TB patients during therapy with anti-MDR-TB regimen in Saint Peter Specialized Hospital Addis Ababa, Ethiopia from January to November 2020.MethodsA cross-sectional study was conducted in MDR-TB patients in Addis Ababa, Ethiopia. A total of 162 patients, who were older than 18 years, had bacteriologically confirmed MDR-TB and on treatment for more than one month were enrolled consecutively from the TB registration book. However, critically sick patients and those who were receiving additional drugs known to cause severe ADRs were excluded. Simple descriptive statistics were used to present the socio-demographic and clinical characteristics of the patients. A logistic regression model was used to assess the association between independent and dependent variables. A p-value <0.05 was considered as statistically significant in all analyses.ResultsMean age of the study participant was 35.9 ± 13.6 years. The prevalence of hypothyroidism was 32 (19.8%). The presence of co-morbidity, being underweight, and prothionamide use were significantly associated with hypothyroidism in MDR-TB patients on treatment.ConclusionHypothyroidism occurs commonly among MDR-TB patients. Presence of co-morbidity, being underweight, and prothionamide drug use are the factors associated with hypothyroidism. Monitoring of thyroid function test during MDR-TB treatment and factors associated with hypothyroidism require attention to prevent complication.

Impact of shorter MDR tuberculosis regimen drugs on heart rate variability in MDR tuberculosis patients at tertiary care hospital

Background: Tuberculosis is major cause of death in India. Analysis of heart rate variability is one of the most popular methods of autonomic nervous system evaluation. Shorter MDR-TB regimen drugs affect both central nervous system as well as peripheral nervous system. Existing research suggests that active pulmonary tuberculosis causes ANS dysfunction. So, by HRV measurement impact of shorter MDR-TB regimen drugs on autonomic dysfunction can be correlated. Aim of the current investigation was to evaluate effect of shorter MDR-TB regimen drugs on cardiac autonomic regulation in MDR-TB patients with respect to heart rate variability as a parameter.Methods: Fifty newly diagnosed MDR-TB patients of either gender on shorter MDR- TB regimen were enrolled in this study after taking consent. After 20 minutes rest, ECG was taken by “physiopac digital polygraph” software for 5 minutes. Two follow-up HRV assessments were done on 2nd month and 4th or 6th month of treatment. HRV was calculated by root mean square deviation of successive differences between adjacent RR intervals (RMSSD) and low frequency and high frequency ratio.Results: Repeated measures ANOVA showed no statistically significant difference in HRV parameters between baseline, 2 months and 6 months groups. So, sympathetic and parasympathetic modulation in terms of HRV remains unchanged during treatment of MDR-TB with shorter MDR-TB regimen drugs.Conclusions: Shorter MDR-TB regimen drugs don’t have any significant impact on HRV in MDR- TB patients, No correlation was observed between HRV and heart rate in MDR-TB patients.

Ambulatory Treatment for Multidrug-Resistant Tuberculosis in Rural Haiti: A Mixed-Methods Study of Social and Economic Factors Affecting Timely Diagnosis and Treatment Success

BACKGROUND AND OBJECTIVES: Patients with MDR-TB in remote areas of Haiti face barriers that delay their ability to initiate and complete treatment. These barriers must be addressed to ensure successful decentralization of MDR-TB treatment. We conducted a mixed-methods study at two MDR-TB facilities in rural Haiti to identify factors that impact MDR-TB treatment initiation and documented treatment response after discharge from hospital. &#x0D; &#x0D; METHODS: We enrolled patients who started MDR-TB treatment at two Zanmi Lasante MDR-TB facilities in Haiti between October 2015 and March 2016. We conducted interviews with patients at discharge to assess factors creating delay in treatment initiation; performed a longitudinal quantitative assessment of patient wellbeing at discharge and for four months after; and conducted a second interview with the same patients and family caregivers to identify obstacles to transition from hospital-based care to ambulatory treatment. Qualitative data were coded into six final conceptual categories representing patient experiences with TB treatment and care. We then explored how the patient experience during transition might affect the score obtained in the quantitative assessment.&#x0D; &#x0D; RESULTS: We enrolled 17 MDR-TB patients and 16 family members. Four patients were identified as having poor clinical response after discharge, characterized by low BMI, low hemoglobin, compromised activities of daily life, food insecurity, depression and other treatment side effects. Patients with poor response also experienced limited social support and difficult living conditions.&#x0D; &#x0D; Factors contributing to delayed treatment initiation were present at discharge and may compromise response. These include financial (lost wages, costly transportation) and logistical barriers to reaching highly centralized treatment facilities. The results highlight the barriers that MDR-TB patients in rural Haiti face to find and successfully complete lifesaving treatment. &#x0D; &#x0D; CONCLUSION: Properly implemented decentralized care will help overcome geographical barriers. Strong nutritional, social and financial support are essential to support appropriate treatment for the disease.

A multi-targeting pre-clinical candidate against drug-resistant tuberculosis

FNDR-20081 [4-{4-[5-(4-Isopropyl-phenyl)- [1,2,4]oxadiazol-3-ylmethyl]-piperazin-1-yl}-7-pyridin-3-yl-quinoline] is a novel, first in class anti-tubercular pre-clinical candidate against sensitive and drug-resistant Mycobacterium tuberculosis (Mtb). In-vitro combination studies of FNDR-20081 with first- and second-line drugs exhibited no antagonism, suggesting its compatibility for developing new combination-regimens. FNDR-20081, which is non-toxic with no CYP3A4 liability, demonstrated exposure-dependent killing of replicating-Mtb, as well as the non-replicating-Mtb, and efficacy in a mouse model of infection. Whole genome sequencing (WGS) of FNDR-20081 resistant mutants revealed the identification of pleotropic targets: marR (Rv0678), a regulator of MmpL5, a transporter/efflux pump mechanism for drug resistance; and Rv3683, a putative metalloprotease potentially involved in peptidoglycan biosynthesis. In summary, FNDR-20081 is a promising first in class compound with the potential to form a new combination regimen for MDR-TB treatment.

CBNAAT Based Identification and Demographic Pattern of Drug Resistant Mycobacterium Tuberculosis in South Kashmir, India- a One Year Retrospective Study

India is the highest TB burden country in the world having an estimated incidence of 26.9 lakh cases in 2019. With a population of 1.32 billion, India has the highest burden of drug resistant TB (DR-TB) in the world. North zone of India is the second highest MDR-TB prevalent zone after the West zone of India. MDR TB treatment involves prolonged treatment with injectable second-line drugs, associated with more adverse effects, suboptimal treatment outcomes and higher risks of mortality compared to patients with drug-sensitive TB and those with lesser resistant forms of TB.&#x0D; Materials methods: This retrospective study was conducted in the department of Microbiology Government Medical College Anantnag, data was analyzed from March 2017 to February 2018. Non-sterile specimens were processed by Modified Petroff Method. Sterile specimens were concentrated by centrifugation and smear and cultures was inoculated from the sediment. CBNAAT assay was performed by Gene Xpert (Cepheid) 4 system according to the manufacturers’ recommendations.&#x0D; Results: Of the total 1497 clinically suspected tuberculosis specimens collected, 1370 (91.5%) were pulmonary and 127 (8.5%) were presumptive extra pulmonary tuberculosis received from different anatomical sites. Maximum clustering of cases was seen in 10-20 years age group. Out of the total 1497 samples 200 were CBNAAT confirmed Mycobacterium Tuberculosis positive samples. In which 155 were pulmonary and 45 were extra pulmonary. The average percentage positivity rate (i.e. percentage of MTB positive samples out of total samples tested) was 13.3% (200/1497). Rifampicin resistance (RR-TB) was seen in 5.5% (11/200) samples. Out of the samples detected positive (200): 155 were pulmonary samples and out of these 155 pulmonary samples 8 were found to be RR MTB 5.1% (8/155). Also out of the 200 positive samples 45 were extra pulmonary and out of these 45 extra pulmonary samples 3 were found to be RR MTB 6.6% (3/45).&#x0D; Conclusion: In this study we found that in our region 5.5% cases of TB were RR-TB, 3.2% were new cases and 13% RR-TB was seen in previously treated cases of MTB. The screening of drug resistance has to be expanded to offer universal DST including expanded DST .The second and most important activity is to strengthen drug resistance surveillance under the various national programs with inclusion of laboratories in the private sector as well. The state level regional studies also give us the opportunity to plan and execute intervention prioritization, based on the drug resistance trends observed.

Projected Use of Pretomanid, Bedaquiline and Linezolid in All-Oral Regimens for Multi-Drug Resistant Tuberculosis from 2021-2025

Background: The World Health Organization is urging countries to facilitate access to fully oral treatment regimens for patients with drug-resistant tuberculosis (DR-TB), which remains a public health crisis. TB Alliance has developed a new 6-month, all-oral regimen for DR-TB called BPaL (comprised of bedaquiline, pretomanid and linezolid), which is recommended by WHO for use under operational research conditions for patients with XDR-TB and in patients who are either unable to tolerate or who have failed MDR-TB treatment. The objective of this study is to project the use of BPaL, along with its components bedaquiline and linezolid, in DR-TB globally until the year 2025. Methods: We conducted semi-structured interviews with National TB Programs in key countries to gather intelligence on country targets and planned regimens for DR-TB treatment for 2021-2025, and developed a deterministic model based on this data to project the use of these drugs globally. Results: The study projects a consistent global growth in the use of bedaquiline, linezolid and BPaL, reaching 190,752, 137,712 and 103,122 patients respectively by 2025. Further, evidence from late-stage trials such as ZeNix, SimpliciTB and TB-PRACTECAL will inform the use of pretomanid-containing regimens. Conclusion: This study can support global health stakeholders including donors, policy makers and manufacturers with planning and budgeting for DR-TB interventions. An estimation of future usage could help us estimate cost of the individual components of DR-TB regimens at different volumes. Above all, national efforts to scale up drug susceptibility testing and implement new treatments will be essential to ensuring they are accessible to all eligible patients in the coming years. Funding Information: The authors Aastha Gupta and Christiaan Mulder received financial support from TB Alliance for the research and writing of this manuscript. The funder reviewed the analysis, methodology and the manuscript, but was not involved in data collection, data interpretation and preparation of the results. Declaration of Interests: C. Mulder and A. Gupta received support and consulting fees from TB Alliance. All other authors have no conflicts to declare. Ethics Approval Statement: Request for ethical approval or informed consent was not deemed necessary as the data collected were reflecting national projections. All respondents agreed with the publication of these data in an anonymized way.

Evidence-based Definition for Extensively Drug-Resistant Tuberculosis.

Rationale: Until 2020, extensively drug-resistant tuberculosis (XDR-TB) was defined as TB with resistance to rifampicin and isoniazid (multidrug-resistant TB [MDR-TB]), any fluoroquinolone (FQ), and any second-line injectable drug (SLID). In 2019, the World Health Organization issued new recommendations for treating patients with drug-resistant TB, substantially limiting the role of SLIDs in MDR-TB treatment and thus putting the definition of XDR-TB into question. Objectives: To propose an up-to-date definition for XDR-TB. Methods: We used a large data set to assess treatment outcomes for patients with MDR-TB exposed to any type of longer regimen. We included patients with bacteriologically confirmed MDR-TB and known FQ and SLID resistance results. We performed logistic regression to estimate the adjusted odds ratios (aORs) for an unfavorable treatment outcome (failure, relapse, death, loss to follow-up), and estimates were stratified by the resistance pattern (FQ and/or SLID) and group A drug use (moxifloxacin/levofloxacin, linezolid, and/or bedaquiline). Measurements and Main Results: We included 11,666 patients with MDR-TB; 4,653 (39.9%) had an unfavorable treatment outcome. Resistance to FQs increased the odds of an unfavorable treatment outcome (aOR, 1.91; 95% confidence interval [CI], 1.63-2.23). Administration of bedaquiline and/or linezolid improved treatment outcomes regardless of resistance to FQs and/or SLIDs. Among patients with XDR-TB, compared with persons receiving no group A drug, aORs for an unfavorable outcome were 0.37 (95% CI, 0.20-0.69) with linezolid only, 0.40 (95% CI, 0.21-0.77) with bedaquiline only, and 0.21 (95% CI, 0.12-0.38) with both. Conclusions: Our study supports a new definition of XDR-TB as MDR-TB and additional resistance to FQ plus bedaquiline and/or linezolid and helps assess the adequacy of this definition for surveillance and treatment choice.

Drug resistance In Mycobacterium Tuberculosis

The COVID-19 pandemic has also had a significant impact on the detection and management of infectious diseases worldwide. As the healthcare resources struggle to deal with the pandemic, there is widespread fear that there will be a rise in other infections and non-communicable diseases. Mycobacterium Tuberculosis remains one of the highest cause of mortality and morbidity in the world with 10 million new cases, 1.4 million deaths and nearly half a million cases of drug-resistant TB, in 2019. The need of the hour is to prevent the rise of drug resistance in TB. The rise in drug resistance can be mainly attributed to failure to adhere to treatment regimens. Recent studies show that the exposure of bacteria to sublethal levels of bacterial antibiotics, promotes cellular mutations, leading to increased mutations promoting drug resistance. Because of the problems associated with the detection and treatment of drug-resistant tuberculosis, it is of paramount importance that we aim to implement stringent measures of primary and secondary prevention against cases of drug-sensitive tuberculosis to prevent the rise of drug resistance. It is important to highlight the importance of DOTS while talking about measures of primary and secondary prevention. The involvement of the multidisciplinary health team and auxiliary health workers to monitor the treatment of affected patients cannot be stressed enough, since this is the most simple and effective way to prevent treatment failure. Furthermore, the cost of treatment of MDR-TB remains out of reach of the middle and lower middle-income strata of society. It is the need of the hour to lower the cost of drugs as well as provide easy and affordable access to rapid investigations to detect drug resistance

Lung Tuberculosis with Multi Drug Resistant Risk in Tertiary Hospital in Middle Java

World TB report from World Health Organization (WHO) in 2017 informed that Indonesia was second country with TB case. Multi Drug Resistance pulmonary infection’s case in Indonesia were 12.000. Kariadi hospital is one of tertiary hospital for pulmonary MDR-TB treatment but, there is no study about risk factor of it yet, so it needed to find risk factors of MDR-TB pulmonary infection in Kariadi hospital. Cross Sectional design using secondary data from Medical Record from January 1st - December 31, 2017 with result of Mycobacterium tuberculosis on GeneXpert sputum examination. Bivariate analysis with Chi square test and multivariate analysis was done by multiple logistic regression. The p value was considered significant if &lt;0.05, all analyzes were 2-tailed. Totally 110 patients were obtained during periode, 55 samples for case and 55 samples for control. There were correlation between smoking habit OR = 3,1 (CI 95% 1,1-8,7), malnutrition OR = 2,9 (CI 95% 1,3-6,3), contact with patient with MDR pulmonary TB infection OR = 12,0 (CI 95% 1,5-97,3), past treatment OR = 81,7(CI 95% 23,4-285,2) and ≥6months past treatment OR = 94,5 (CI 95% 12,1-736,2. Risk factor that could influence together were contact with patient with MDR pulmonary TB infection OR = 34,5 (CI 95% 2,6-464,5), past treatment OR = 39,4 (CI 95% 8,3-186,3) and ≥ 6months past treatment OR = 12,4 (CI 95% 1,3-117,7). Risk factors for the incidence of pulmonary MDR TB infection are past contact with patient with MDR pulmonary TB infection, past treatment and ≥ 6months past treatment.

The use of reserve drugs in the chemotherapy of children and adolescents with tuberculosis

Introduction. The incidence of tuberculosis in children and adolescents is considered one of the most significant epidemiological indicators, which reflects the overall epidemic situation for tuberculosis. An urgent problem is the fact that the effectiveness of treatment of tuberculosis with MDR/XDR MBT in children and adolescents is not reflected in official statistics, and the tolerability of new anti-tuberculosis drugs in children with tuberculosis is not sufficiently studied at present. One of the drugs that can be used in the treatment of MDR-TB in children is linezolid. Objective. to evaluate the safety and efficacy of linezolid in chemotherapy regimens for drug-resistant tuberculosis in children. Results. in the structure of clinical forms of infiltrative tuberculosis — (32.0%), the primary tuberculosis complex was detected in 8 people (16.0%), TB of intra-thoracic lymph nodes also in 8 people (16.0%). MBT resistance to cycloserine and linezolid has not been reported in any patients. All patients received linezolid (100%). The development of undesirable side effects was observed in 14 people (28.0%). Linezolid caused in 3 people (6.0%) (adolescents 13 — 17 years old) undesirable adverse reactions of the type of polyneuropathy. The cessation of bacterial excretion was observed after 1 month in 100 % of cases. All children showed positive clinical dynamics and normalization of blood parameters in the period from 2 to 6 months of treatment. Positive radiological dynamics were also observed in the period from 2 to 6 months of treatment in the form of closure of the decay cavities, compaction, calcification and resorption of foci. Conclusion. Linezolid is a promising drug in children with tuberculosis who need the use of reserve drugs, since clinical efficacy is noted, MBT resistance is rarely developed, and the frequency of undesirable side reactions of regimens with the inclusion of linezolid does not exceed the frequency of those when prescribing regimens without the inclusion of linezolid

A rational pharmacotherapeutic study of the prevalent prescription patterns of delamanid, ofloxacin, levofloxacin, and bedaquiline among the multi-drug resistant tuberculosis patients in global multi-centre tertiary care hospitals

Background: Delamanid, a nitro-dihydro-imidazooxazole, is a bactericidal cell wall methoxy-mycolic and keto-mycolic acids biosynthesis inhibitor in actively replicating, dormant, and intracellular tuberculosis, and both drug-susceptible and drug-resistant strains of M. tuberculosis and M. kansasii, decreasing hydrophobicity and facilitating better bacterial drug penetration. Delamanid promotes intracellular generation of microbiocidal nitrogen oxidative intermediaries including nitric oxide, toxic even to dormant M. tuberculosis. Ofloxacin, the racemic mixture and levofloxacin, the S-or levorotatory isomer of ofloxacin, are bactericidal to M. tuberculosis, MAC, M. fortuitum, and other atypical mycobacteria, with inhibitory effect on DNA gyrase, DNA topoisomerase IV and IL-1α, IL-6, IL-8. Bedaquiline, a novel diarylquinoline, inhibits mycobacterial adenosine triphosphate synthase of M. tuberculosis, disrupting mycobacterial energy metabolism and replication. Bedaquiline’s initial bacteriostatic action is followed by a bactericidal effect after 5-7 days. The objective was to perform a rational pharmacotherapeutic study of the prevalent prescription patterns of delamanid, ofloxacin, levofloxacin, and bedaquiline, among the multi-drug resistant tuberculosis patients, in global multi-centre tertiary care hospitals.Methods: A multi-centre, retrospective, observational and analytical study of clinical prescriptions of 100 multi-drug resistant tuberculosis patients in hospitals, were performed. For 24-48 weeks, these patients had been prescribed anti-tubercular drugs, like delamanid 100 mg and ofloxacin 400 mg twice daily, levofloxacin 750 mg and bedaquiline 400 mg once daily followed by 200 mg thrice weekly, as part of MDR-TB treatment regimens. The no. of prescriptions for each drug were recorded, and the corresponding prescription rates were statistically derived in percentages. Results: Delamanid was most commonly prescribed (32 prescriptions, 32%), followed by ofloxacin (29 prescriptions, 29%), levofloxacin (24 prescriptions, 24%), and bedaquiline (15 prescriptions, 15%). The completeness of the prescription contents, the dose of drug, the duration of treatment, the instructions of medication, the frequency of drug intake, the name of the drug and the dosage form of the drug were observed in 100% of prescriptions.Conclusions: Prescription frequency of delamanid was followed by ofloxacin, levofloxacin and bedaquiline. Prescription content analyses showed 100% completeness.

Culture conversion at six months in patients receiving bedaquiline- and delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis

Rifampicin-resistant/multidrug-resistant (RR/MDR) and extensively drug-resistant (XDR) strains of M. tuberculosis (TB) are serious public health problem in Kazakhstan. In 2012 and 2013, stringent regulatory authorities approved the first new TB drugs in fifty years, bedaquiline and delamanid, offering hope for more effective and less toxic MDR-TB treatment. The endTB Observational Study is a multi-country study that enrolled patients receiving a bedaquiline- or delamanid-containing regimen for RR/MDR-TB between 01 April 2015 and 30 September 2018. In Kazakhstan, 675 patients participated in the study; all had at least 6-months or longer of follow-up after the start of treatment. The present analysis focuses on endTB Observational Study patients living in Kazakhstan who had a positive baseline sputum culture (220 patients) and initiated a bedaquiline- or delamanid-containing regimen between February 1, 2016 and March 31, 2018. Of them, 195 (89%) of patients experienced culture conversion within six months.

Discordance of the Repeat GeneXpert MTB/RIF Test for Rifampicin Resistance Detection Among Patients Initiating MDR-TB Treatment in Uganda.

BackgroundThe Global Laboratory Initiative (GLI) guidelines recommend repeat for GeneXpertMTB/RIF (XpertMTB/RIF) in patients with a low pretest probability of rifampicin resistance (RR).MethodsThis was a cross-sectional study using results of sputum specimens collected from participants screened for the STREAM 2 trial. We recruited all patients with XpertMTB/RIF RR-TB detected who were referred for RR/multidrug-resistant (MDR) TB treatment initiation at Mulago National Referral Hospital, Kampala, between September 2017 and October 2019. At baseline, smear microscopy, repeat XpertMTB/RIF, Xpert Ultra, and MTBDRplus assays were done on sputum specimens. Culture-based drug susceptibility testing (DST) was performed on discordant specimens. We analyzed the prevalence and factors associated with discordance between initial and repeat XpertMTB/RIF RR and false XpertMTB/RIF RR. False XpertMTB/RIF RR was defined as no RR detected by any of Xpert Ultra, LPA, or culture DST (reference comparator).ResultsA total of 126/130 patients had repeat XpertMTB/RIF results, of whom 97 (77.0%) had M. tuberculosis detected, 81 (83.5%) had RR detected, and 1 (1.0%) had RR indeterminate. The prevalence of discordant XpertMTB/RIF RR was 15/96 (15.6%), whereas false XpertMTB/RIF RR prevalence was 10/96 (10.4%).Low–bacillary load sputum specimens were more likely to have discordant XpertMTB/RIF RR and false XpertMTB/RIF RR results (adjusted odds ratio [aOR], 0.04; 95% CI, 0.00–0.37; P = .01; aOR, 0.02; 95% CI, 0.01–0.35; P = .01, respectively).ConclusionsOur findings show a high false-positive rifampicin resistance rate in low–TB burden patients, which calls for repeat testing in order to prevent unnecessary prescription of anti-MDR-TB therapy.