Treatment outcomes of multidrug resistant tuberculosis (MDR TB) treated with bedaquiline under programmatic management of drug resistant tuberculosis at a tertiary care hospital in Punjab, India.

INTRODUCTION: MDR TB is a serious global concern which is hampering TB elimination goals badly. Standardized MDR TB regimen had high default rates, more side effects and poor treatment outcomes. Bedaquiline is a newer anti-tubercular drug which has made oral regimens possible for MDR TB. We aimed to study the outcomes of MDR TB patients treated with Bdq containing regimens. METHODS: 155 patients of MDR TB on Bdq containing regimen enrolled at GMC, Patiala under NTEP from 2017 to 2020 were enrolled retrospectively. RESULTS: Out of 155 patients enrolled, 82 (52.9 %) were cured, 31 (20 %) completed treatment, 18 (11.6 %) defaulted, 22 (14.2 %) died and 2 (0.12 %) failed treatment. CONCLUSION: Bdq is well tolerated with very less side effects and has better outcomes as compared to standard MDR regimens which were followed earlier.

A Comprehensive Review on Long vs. Short Regimens in Multidrug-Resistant Tuberculosis (MDR-TB) Under Programmatic Management of Drug-Resistant Tuberculosis (PMDT).

This comprehensive review delves into the intricate landscape of multidrug-resistant tuberculosis (MDR-TB) treatment within the programmatic management of drug-resistant tuberculosis (PMDT) framework. MDR-TB poses a substantial global health threat, necessitating targeted approaches for effective management. The analysis explores the historical evolution, efficacy, safety profiles, and implementation challenges associated with long and short regimens. The findings underscore the importance of individualized clinical practices, considering patient-specific factors, and the need for ongoing monitoring within PMDT programs. Recommendations advocate for integrating advanced diagnostics, continuous surveillance, and training for healthcare professionals. The review concludes with a nuanced outlook on long versus short regimens, emphasizing a balanced approach and the imperative role of collaborative efforts in shaping the future of MDR-TB treatment. This synthesis contributes to the ongoing discourse, providing valuable insights for healthcare practitioners, policymakers, and researchers working toward optimizing outcomes for individuals afflicted with MDR-TB.

Shorter regimens improved treatment outcomes of multidrug-resistant tuberculosis patients in Tanzania in 2018 cohort.

OBJECTIVE: In 2018, shorter treatment regimens (STR) for people with drug-resistant tuberculosis (DR-TB) were introduced in Tanzania and included kanamycin, high-dose moxifloxacin, prothionamide, high-dose isoniazid, clofazimine, ethambutol and pyrazinamide. We describe treatment outcomes of people diagnosed with DR-TB in a cohort initiating treatment in 2018 in Tanzania. METHODS: This was a retrospective cohort study conducted at the National Centre of Excellence and decentralised DR-TB treatment sites for the 2018 cohort followed from January 2018 to August 2020. We reviewed data from the National Tuberculosis and Leprosy Program DR-TB database to assess clinical and demographic information. The association between different DR-TB regimens and treatment outcome was assessed using logistic regression analysis. Treatment outcomes were described as treatment complete, cure, death, failure or lost to follow-up. A successful treatment outcome was assigned when the patient achieved treatment completion or cure. RESULTS: A total of 449 people were diagnosed with DR-TB of whom 382 had final treatment outcomes: 268 (70%) cured; 36 (9%) treatment completed; 16 (4%) lost to follow-up; 62 (16%) died. There was no treatment failure. The treatment success rate was 79% (304 patients). The 2018 DR-TB treatment cohort was initiated on the following regimens: 140 (46%) received STR, 90 (30%) received the standard longer regimen (SLR), 74 (24%) received a new drug regimen. Normal nutritional status at baseline [adjusted odds ratio (aOR) = 6.57, 95% CI (3.33-12.94), p < 0.001] and the STR [aOR = 2.67, 95% CI (1.38-5.18), p = 0.004] were independently associated with successful DR-TB treatment outcome. CONCLUSION: The majority of DR-TB patients on STR in Tanzania achieved a better treatment outcome than on SLR. The acceptance and implementation of STR at decentralised sites promises greater treatment success. Assessing and improving nutritional status at baseline and introducing new shorter DR-TB treatment regimens may strengthen favourable treatment outcomes.

MDR-TB in Pakistan: Challenges, efforts, and recommendations.

Tuberculosis (TB), a global health concern is also a leading cause of mortality and morbidity across Pakistan affecting a major proportion of the population. The absence of an integrated system to control the spread of TB has led to a rise in multidrug resistant strains of TB (MDR-Tb) which do not exhibit any sensitivity towards the first line therapy for TB. Such adverse circumstances call for effective planning strategies to mitigate the health hazards of MDR-TB. This article briefly highlights the challenges encountered by the already burdened healthcare system and suggests relatively inexpensive approaches to tackle the ongoing crisis associated with MDR-TB on a national scale.

Drug resistance patterns, treatment outcomes and factors affecting unfavourable treatment outcomes among extensively drug resistant tuberculosis patients in Pakistan; a multicentre record review.

Background: Extensively drug resistant tuberculosis (XDR-TB) is considered as a major threat to global health. This study aimed to analyse the treatment outcomes and identify the factors significantly associated with unfavourable treatment outcomes among XDR-TB patients. Methods: We conducted a retrospective observational study at 10 Programmatic Management Units of the National Tuberculosis Control Program of Pakistan. The Electronic Nominal Recording Reporting System records were used to collect data of all eligible XDR-TB patients registered at the study sites between March 2012 and August 2018. Treatment outcomes were analysed as per the standard criteria. Factors associated with unfavourable treatment outcomes were analysed by using multivariate binary logistic regression analysis. Results: Out of the total 184 patients, 59 (32.1%) completed their treatment successfully. Whereby, 83 patients (45.1%) died, 24 (13%) had treatment failure, and 11 (6%) were lost to follow-up. Treatment outcomes were not evaluated in 7 (3.8%) patients. Factors significantly associated with unfavourable treatment outcomes included; conventional therapy with bedaquiline, unfavourable interim treatment outcomes and occurrence of adverse drug events (negative association). Conclusion: Treatment success rate in the study cohort was sub-optimal (i.e., <75%). The poor success rate and high mortality are concerning, and requires immediate attention of the program managers and clinicians.

Study of treatment outcomes of multidrug-resistant tuberculosis under programmatic conditions and factors influencing the outcomes in Hyderabad District.

BACKGROUND: Treatment outcomes for Multidrug-Resistant Tuberculosis (MDR TB) is generally poor. The study aims to know about the treatment outcomes of MDR-TB under programmatic conditions in Hyderabad District and to analyze the factors influencing the treatment outcomes. METHODS: This is a retrospective study in which 377 patients of Hyderabad district, Telangana state who were diagnosed with MDR TB and registered at Drug Resistance TB Treatment site of Government General & Chest Hospital, Hyderabad from 4th quarter 2008 to 4th quarter 2013 were included in the study. Impact of Demographic factors (age, sex; Nutritional status (BMI); Co-morbid condition (Diabetes, HIV, Hypothyroidism); Programmatic factors (time delay in the initiation of treatment); Initial Resistance pattern on the outcomes were studied and analyzed. RESULTS: The treatment outcomes of Multidrug-Resistant Tuberculosis under Programmatic Conditions were: 57% cured, 21.8% died, 19.6% defaulted, 1.1% failed and 0.5% switched to XDR. Age, Sex, BMI had a statistically significant impact on treatment outcomes. Hypothyroidism and Delay in the initiation of treatment >1 a month had an impact on the outcomes though not statistically significant. NO impact on treatment outcomes was found when Rifampicin resistance & INH sensitive patients were compared with those resistant to both INH and Rifampicin. CONCLUSION: To reduce MDR-TB transmission in the community, improvement of treatment outcomes, via ensuring adherence, paying special attention to elderly patients is required. The Programmatic Management of Drug Resistance Tuberculosis (PMDT) should seriously think of providing Nutritional support to patients with low BMI to improve outcomes. In the programmatic conditions if we could address the problems like delay in initiation of treatment and proper management of comorbidities like HIV, Diabetes, Hypothyroidism would definitely improve the treatment outcomes.

Frequency and Factors Associated With Adverse Events Among Multi-Drug Resistant Tuberculosis Patients in Pakistan: A Retrospective Study.

Background: Treatment of multi-drug resistant tuberculosis (MDR-TB) for a prolonged period with comparatively less effective and more toxic second-line anti-TB drugs is associated with greater incidence of adverse events. Study aim: This study aimed to evaluate the frequency and factors associated with occurrence of adverse events among patients with MDR-TB attending the Bahawal Victoria Hospital, Bahawalpur, Pakistan. Study design: This retrospective study included all patients with MDR-TB who were registered and treated at the study site between June 2014 and December 2016 and had their treatment outcomes available at the time of data collection (i.e., November 2018). Measures and outcomes: The Electronic Nominal Record System (ERNS) records, medical charts of patients, and laboratory reports were reviewed to obtain the data. Adverse events were reported as per the standard criteria recommended by the WHO. Multivariate binary logistic regression was used to find the independent factors associated with the occurrence of adverse events. Results: A total of 179 patients with MDR-TB were included in the final analysis. Out of these, 114 (63.7%) patients experienced at least one adverse event during the course of their treatment. Depression was the most common adverse events (33%), followed by nausea and vomiting (27.4%) and arthralgia (27.4%). The factors associated with the occurrence of adverse events included presence of comorbidity (adjusted odds ratio [AOR] 2.951; 95% CI 1.423, 6.118) and being employed (AOR 3.445; 95% CI 1.188, 9.993). Conclusion: Adverse events were prevalent in this cohort, however, resolved with the effective management approaches. Patients with identified factors for occurrence of adverse events need special attention and enhanced clinical management.

A comparison of patient treatment pathways among multidrug-resistant and drug-sensitive TB cases in Delhi, India: A cross-sectional study.

BACKGROUND: The delay in the diagnosis and treatment initiation of patients with MDR-TB worsens individual prognosis and increases the risk of disease transmission in the community. These delays have been attributed to delay in treatment-seeking by the patient and shifting to multiple healthcare facilities before being tested and diagnosed through India's National Tuberculosis Elimination Program (NTEP). OBJECTIVE: to identify treatment pathways in patients with MDR-TB from the time of onset of symptoms and treatment seeking until diagnosis at a PMDT site and subsequent treatment initiation. We also compared these characteristics with those of patients with DS-TB. METHODS: We recruited a total of 168 patients with MDR-TB and DS-TB each, in Delhi. Data were analyzed using IBM SPSS Version 25. RESULTS: The mean (SD) patient delay for initial treatment-seeking was 20.9 (15.9) days in patients with MDR-TB, and 16.1 (17.1) days in patients with DS-TB (p < 0.001). The median time from visit to the first healthcare facility (HCF) until confirmation of MDR-TB diagnosis was 78.5 days, and until treatment initiation was 102.5 days. Among patients with DS-TB, the time interval from a visit to the first HCF until the initiation of ATT-DOTS was 61.5 days.. Patients diagnosed with DS-TB, whose first source of treatment was a private facility (n = 49), reported a significant delay in the initiation of ATT-DOTS (p < 0.001). CONCLUSIONS: Despite the introduction of universal drug sensitivity testing in individuals having presumptive MDR-TB, a significant delay in the diagnosis and initiation of effective MDR-TB treatment persists as a major public health challenge in India.

Factors associated with mortality to drug-resistant tuberculosis and their programmatic management in treatment centres of Punjab, Pakistan.

OBJECTIVE: To describe the characteristics and assess the factors of mortality in drug-resistant tuberculosis patients. METHODS: This retrospective study was conducted at 11 programmatic management of drug-resistant tuberculosis centres located in different cities of the Punjab province of Pakistan, and comprised record of patients with drug-resistant tuberculosis from January 2010 to September 2015. Data was retrieved from patient medical records using electronic nominal review system of the provincial tuberculosis control programme. Cox's proportional hazards model was performed to identify the factors for death. SPSS 17 was used for data analysis. RESULTS: Of the 1,136 patients, 472(41.5%) died during treatment and 664(58.5%) were declared cured or their treatment was completed. Of those who expired, 97(20.6%) expired within 3 months of the start of the treatment. Men had higher rates of death which was not significantly associated with the drug-resistant tuberculosis mortality (p>0.05). CONCLUSIONS: The number of patients who died from drug-resistant tuberculosis treatment was relatively high.

Prevalence and drug resistance pattern of MDR TB in retreatment cases of Punjab, Pakistan.

OBJECTIVE: To determine the prevalence and resistance pattern of multidrug-resistant tuberculosis. METHODS: This cross-sectional study was carried out from January 2010 to June 2014 in nine tertiary care hospitals implementing programmatic management of drug-resistant tuberculosis in Punjab, and comprised retreatment tuberculosis cases. Data was collected from the Electronic Nominal Review System. SPSS 17 was used for data analysis. RESULTS: Of the 1,250 cases, 861(69%) were of multidrug-resistant tuberculosis confirmed through drug sensitivity testing. The mean age was 32 (±13.5 SD) years. Besides, 664(53%) were males and 1,208(97%) resided in urban areas of Punjab. Multidrug-resistant tuberculosis was found to be more prevalent in the most productive age group, i.e. 15-45 years, with 709(57%) cases (p<0.05), in urban areas1, 208(97%) cases (p<0.05) and in the pulmonary site 852(68%) cases (p<0.05). Overall, 391(41%) cases showed resistance to all first-line anti-tuberculosis drugs while 239(28%) showed resistance to oral first-line drugs. Besides, 526(42%) cases showed resistance to fluoroquinolones and 650(52%) to second-line drugs. Of them, 420(81%), (p<0.05) patients showed highly significant resistance to fluoroquinolones and 26(5%) to ethionamide. CONCLUSIONS: There is a need to fully implement national tuberculosis guidelines with a focus on expansion and effective implementation of directly observed therapy short course in order to prevent further emergence of drug resistance.

Could transformation mechanisms of acetylase-harboring pMdT1 plasmid be evaluated through proteomic tools in Escherichia coli?

UNLABELLED: Escherichia coli is a commensal microorganism of the gastrointestinal tract of animals and humans and it is an excellent model organism for the study of antibiotic resistance mechanisms. The resistance transmission and other characteristics of bacteria are based on different types of gene transfer occurring throughout the bacterial evolution. One of which is horizontal gene transfer that allows us to understand the ability of bacteria to acquire new genes. One dimensional and two dimensional electrophoresis (2-DE) techniques were performed in order to identify and characterize the proteome of two E. coli strains: Electromax DH10B, a transformation-ready strain; and TF-Se20, the Electromax DH10B that contains the aac(6')-Ib-cr4-harboring pMdT1 plasmid. After 2-DE and subsequent analysis by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS), it was possible to identify 76 distinct proteins on the TF-Se20 strain, whereas 71 had a known function. From Electromax DH10B strain, 72 different proteins were identified of which 71 were associated with a biological process. The protein of interest, aminoglycoside N-(6')-acetyltransferase type 1, was identified by MALDI-TOF MS. The liquid chromatography-tandem mass spectrometry (LC-MS/MS) technique was performed to determine its sequence. Seventy six percent of the acetylase sequence was reconstructed only in the TF-Se20 strain, representing the single protein associated to antibiotic resistance. MALDI-TOF MS and LC-MS/MS approaches allowed us to determine the total proteome of both strains, as well as the acetylase sequence. Both of them enhance the ability to obtain more accurate information about the mechanisms of antimicrobial resistance. The pMdT1 plasmid brings a new perspective in understanding the metabolic processes that lead to antibiotic resistance. BIOLOGICAL SIGNIFICANCE: This study highlights the importance of proteomics and bioinformatics in understanding mechanisms of gene transfer and antibiotic resistance. These two approaches allow to compare the protein expression in different samples, as well as different biological processes related to each protein.

Prevalence of Multidrug Resistant Pulmonary Tuberculosis in North Bihar.

INTRODUCTION: Multidrug resistant tuberculosis (MDR-TB) is caused by Infection with Mycobacterium tuberculosis which is resistant to both isoniazid (INH) and rifampicin (RIF), with or without any other anti tubercular drug. It is caused by resistant mutant strains due to inadequate treatment and poor compliance. Due to time taking conventional diagnostic methods, drug resistant strains continue to spread. Therefore rapid diagnosis and treatment of MDR-TB strains are prerequisites for the worldwide fight against TB. OBJECTIVE: To determine the prevalence of MDR TB in North Bihar by molecular diagnostic method and to facilitate early diagnosis and treatment. Also, to find out the number of those diagnosed cases who were successfully initiated the treatment in MDR TB Centre of DMCH. MATERIALS AND METHODS: This six month observational study was carried out in IRL Darbhanga, Damien TB research Centre of the Darbhanga Medical College and Hospital, Bihar, India. During the period of February-July 2014, 256 sputum samples were collected from suspected cases of multidrug resistant tuberculosis, from 6 districts of North Bihar around Darbhanga. These samples were subjected to routine microscopy and culture to detect Mycobacterium tuberculosis. Positive cases were subjected to drug sensitivity test by a molecular diagnostic method, Using Genotype MTBDR plus kit. RESULT: Out of 256 sputum samples from suspected cases of MDR TB, 122 cases were microscopy positive for tuberculosis. Among these 122 cases, tuberculosis was confirmed by PCR in 114 cases. Finally with the help of Line Probe Assay (LPA), 39(15%) samples were found to have resistance to both INH and Rifampicin. Male female ratio was 4:1. CONCLUSION: The Prevalence of Multi drug resistant pulmonary tuberculosis in North Bihar is 15%. It needs early diagnosis by molecular diagnostic method and prompt treatment to reduce the spread of MDR TB cases.

Western Pacific Regional Green Light Committee: progress and way forward.

The Western Pacific Regional Green Light Committee (rGLC WPR) was established in 2011 to promote the rational scale-up of programmatic management of drug-resistant tuberculosis (PMDT). We reflect on its achievements, consider the challenges faced, and explore its potential future role. Achievements include the supervision and support of national PMDT action plans, increased local ownership, contextualized guidance, and a strong focus on regional capacity building, as well as a greater awareness of regional challenges. Future rGLC activities should include (1) advocacy for high-level political commitment; (2) monitoring, evaluation, and supervision; (3) technical support and contextualized guidance; and (4) training, capacity building, and operational research. Regional activities require close collaboration with both national and global efforts, and should be an important component of the new Global Drug-resistant TB Initiative.