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Background: Drug resistant tuberculosis (DR-TB) continues to be a significant global public health concern despite the availability of effective TB medicines. Equally, delayed DR-TB treatment initiation is associated with increased morbidity, amplified resistance, transmission risk and poor treatment outcomes. This study aimed to investigate treatment delays and identify predictors of delayed treatment initiation among DR-TB patients in Uganda., Method: A retrospective study was conducted using routine DR-TB national case registration data between January 2012 and December 2019. Stata version 15 was used to run uni-variate analysis to describe patient characteristics using frequencies and percentages; bivariate analysis to identify significant differences in median times to treatment initiation; and logistic regression model was fitted, and adjusted odds ratio (AOR) with 95% confidence interval was used to identify factors associated with DR-TB treatment delay., Results: A total of 2,166 DR-TB patients were included in this study. The median treatment initiation delay was 10 days. Approximately 57% of DR-TB patients experienced delays in starting their treatment beyond the acceptable 7-day timeframe. Being diagnosed as RR-TB [AOR = 1.22; 95% CI: 1.08-1.37], and being a recurrent TB patient [AOR = 1.22; 95% CI: 1.01-1.47] were associated with treatment delays. Patients with previous history of 'lost to follow-up' (LTFU), failure and being diagnosed as Pre-XDR-TB were less inclined to delay DR-TB treatment., Conclusion: Several DR-TB patients experienced treatment delay. The delay was significant among patients diagnosed as RR-TB and those with TB treatment history of recurrent TB. This highlights the need for heightened vigilance among healthcare workers when managing DR-TB patients with a history of past TB treatment and those diagnosed as RR-TB to minimize delays. Furthermore, future research should investigate a comprehensive list of variables influencing the timing of treatment initiation after diagnosis. An in-depth understanding of the effects of these factors can inform targeted interventions to optimize treatment strategies for improved DR-TB patient outcomes., Competing Interests: Declarations. Ethics approval and consent to participate: The study employed routine NTLP DR-TB program data without patient participation, but gained administrative authorization to access the data from NTLP. As the study did not utilize any personal identifiable information, obtaining patient consent was unnecessary. Moreover, there were no anticipated risks or advantages to the patients resulting from the examination of this data. Nevertheless, the researchers obtained ethical approval from both the Makerere School of Social Sciences Research and Ethics Committee (REC) with a reference number (MAKSSREC 11.22.610/PRI) and the Uganda National Council for Science and Technology(UNCST) with a reference number HS2653ES. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Drug-resistant tuberculosis (DR-TB) poses a significant global health challenge and requires treatment with potentially toxic second-line anti-TB drugs. Assessing the health-related quality of life (HRQoL) of DR-TB patients is crucial, given the impact of disease and treatment on their well-being. This study aimed to evaluate HRQoL among DR-TB patients undergoing treatment in Botswana and identify predictors of variability during the treatment period., Methods: A cross-sectional study involving almost all the eligible clients in the DR-TB treatment database was conducted at four of the six DR-TB sites in Botswana. The SF-36v2-based questionnaire was administered to all patients receiving treatment between March 2022 and June 2023. Data analysis was performed with QualityMetric Inc., LLC PRO CoRE scoring software and Stata 13.1 for the HRQoL scoring and regression analyses, respectively. A score ≤ 47 on the norm-based scoring (NBS) indicated poor HRQoL. Shorter, all-oral DR-TB regimens were introduced since 2018 but Botswana had not yet fully implemented those in the years 2022/2023. Patients had to go on treatment for 18-24 months during the time of the study., Results: Seventy-two of the 81 eligible participants were enrolled. Participants on treatment for 13-24 months exhibited better HRQoL scores (53.3 ± 8.4) than those in the initial (0-12 months, 46.9 ± 10.8) and latter phases of treatment (> 24 months, 44.3 ± 10.1) for the Physical Component Summary (PCS) even though it was not statistically significant (p = 0.0996). The mental component summary (MCS) scores were 41.6 ± 11.3, 51.6 ± 7.8, and 41.3 ± 10.7 for 0-12, 13-24, and > 24 months, respectively, with significant differences observed for the MCS (p = 0.0097). Multivariate analysis identified renal impairment as a predictor of PCS variability, while alcohol consumption, prior TB treatment, and lung cavity on chest X-ray imaging predicted MCS variability., Conclusion: DR-TB patients in Botswana demonstrated comparable or improved HRQoL (> 47 NBS) in their second year (13-24 months) of treatment, contrasting with poorer HRQoL scores in the initial and final years for both the PCS and MCS. The findings underscore the necessity for tailored psychosocial support, advocated for its integration into the Botswana National TB Program as a pilot initiative before widespread implementation., Competing Interests: Declarations. Ethical approval and consent to participate: All ethical clearance procedures were followed before the start of the study. Ethical approval was obtained from the University of Botswana Institutional Review Board (IRB) under reference number UBR/RES/IRB/BIO/GRAD/158 and the Ministry of Health Review Board under permit number HPDME: 13/18/1 of 01 December 2021, and permission to conduct the study on sites was granted by the PMH, NRH, SMH and GPH IRBs. All respondents were requested to sign a consent form and were informed that participation in the study is voluntary. All participants who successfully completed the study questionnaire were included in the analysis. All participants provided written informed consent before study participation. Clinical trial number: not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: Multidrug-resistant/rifampicin-resistant tuberculosis is a major obstacle to successful tuberculosis control. The recommendation by the WHO to use bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaL(M)) for 6 months, based on results of two trials with high efficacy and low toxicity, has revolutionized treatment options., Methods: In this study, representatives of the Tuberculosis Network European Trials group in 44 of 54 countries of the WHO Europe region documented the availability of the medicines and drug susceptibility testing (DST) of the BPaL(M) regimen through a structured questionnaire between September and November 2023., Results: In total, 24 of 44 (54.5%), 42 of 44 (95.5%), 43 of 44 (97.7%), and 43 of 44 (97.7%) countries had access to pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, 23 of 44 (52.3%) countries had access to all the drugs composing the BPaL(M) regimen. In total, 21 of 44 (47.7%), 37 of 44 (84.1%), 40 of 44 (90.9%), and 41 of 44 (93.2%) countries had access to DST for pretomanid, bedaquiline, linezolid, and moxifloxacin, respectively. Overall, DST was available for all medicines composing the BPaL(M) regimen in 21 of 44 (47.7%) countries, including countries where pretomanid DST was available at specialized laboratories. The availability of DST for the drugs the countries had access to, varied from 87.5% to 95.3% (pretomanid 21 of 24 (87.5%), bedaquiline 37 of 42 (88.1%), linezolid 40 of 43 (93.1%) and moxifloxacin 41 of 43 (95.3%))., Discussion: In only about half of the countries participating in the survey, clinicians had access to all the BPaL(M) regimen drugs. A complete DST for the BPaL(M) medicines was possible in less than half of the countries, because of the low accessibility of DST for pretomanid. Equal access to new regimens is urgently needed in Europe and a rapid scale up of DST, especially for pretomanid, is important to prevent unnoticed spread of drug resistance., (Copyright © 2024 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Regimens for the treatment of rifampicin-resistant tuberculosis currently rely on the use of QT-prolonging agents. Using data from the randomized controlled trial, TB-PRACTECAL, we investigated differences in QTcF among participants in the three interventional arms: BPaL (bedaquiline, pretomanid, and linezolid), BPaLC (BPaL with clofazimine), and BPaLM (BPaL with moxifloxacin). Additionally, we assessed whether age, body mass index, and country were causally associated with QTcF prolongation. The trial included participants from South Africa, Uzbekistan, and Belarus. A post hoc analysis of electrocardiogram data was undertaken. Random effects regression was used to model QTcF longitudinally over 24 weeks and causal frameworks guided the analysis of non-randomized independent variables. 328 participants were included in BPaL-based arms. The longitudinal analysis of investigational arms showed an initial QTcF steep increase in the first week. QTcF trajectories between weeks 2 and 24 differed slightly by regimen, with highest mean peak for BPaLC (QTcF 446.5 ms). Overall, there were 397 QTcF >450 ms (of 3,744) and only one QTcF >500 ms. The odds of QTcF >450 ms among participants in any investigational arm, was 8.33 times higher in Uzbekistan compared to Belarus (95% confidence interval: 3.25-21.33). No effect on QTcF prolongation was found for baseline age or body mass index (BMI). Clinically significant QTc prolongation was rare in this cohort of closely monitored participants. Across BPaL-based regimens, BPaLC showed a slightly longer and sustained effect on QTcF prolongation, but the differences (both in magnitude of change and trajectory over time) were clinically unimportant. The disparity in the risk of QTc prolongation across countries would be an important factor to further investigate when evaluating monitoring strategies., Clinical Trials: This study is registered with ClinicalTrials.gov as NCT02589782., Competing Interests: The authors declare no conflict of interest.

Objective: We aimed to evaluate the sputum culture conversion time of DR-TB patients and its related factors., Methods: PubMed, The Cochrane Library, Embase, CINAHL, Web of Science, CNKI, Wan Fang, CBM and VIP databases were electronically searched to collect studies on sputum culture conversion time in patients with DR-TB. Meta-analysis was performed by using the R 4.3.0 version and Stata 16 software., Results: A total of 45 studies involving 17373 patients were included. Meta-analysis results showed that the pooled median time to sputum culture conversion was 68.57 days (IQR 61.01,76.12). The median time of sputum culture conversion in patients with drug-resistant tuberculosis was different in different WHO regions, countries with different levels of development and different treatment schemes. And female (aHR = 0.59,95%CI: s0.46,0.76), alcohol history (aHR = 0.70,95%CI:0.50,0.98), smoking history (aHR = 0.58,95%CI:0.38,0.88), history of SLD use (aHR = 0.64,95%CI:0.47,0.87), BMI < 18.5 kg/m 2 (aHR = 0.69,95%CI:0.60,0.80), lung cavity (aHR = 0.70,95%CI:0.52,0.94), sputum smear grading at baseline (Positive) (aHR = 0.56,95%CI:0.36,0.87), (grade 1 + ) (aHR = 0.87,95%CI:0.77,0.99), (grade 2 + ) (aHR = 0.81,95%CI:0.69,0.95), (grade 3 + ) (aHR = 0.71,95%CI:0.61,0.84) were the related factor of sputum culture conversion time in patients with DR-TB., Conclusion: Patients with DR-TB in Europe or countries with high level of economic development have earlier sputum culture conversion, and the application of bedaquiline can make patients have shorter sputum culture conversion time. Female, alcohol history, smoking history, history of SLD use, BMI < 18.5 kg/m 2 , lung cavity, sputum smear grading at baseline (Positive, grade 1 + , grade 2 + , grade 3 + ) may be risk factors for longer sputum culture conversion time. This systematic review has been registered in PROSPERO, the registration number is CRD42023438746., (© 2024. The Author(s).)

Tuberculosis (TB) updates and guidelines have been published rapidly in last few years. The WHO and RNTCP have recommended suggestions that have changed the diagnostics and therapeutics paradigm in 2019. The rapid nature of these changes need to be appraised at the pulmonologist end. We conducted a google survey to study these gaps and subsequently review TB in 2019 focusing on the gaps in the survey. We narrate a short review covering the important diagnostic and therapeutic aspects in brief. We discuss the results of our google survey to address the knowledge gaps. Diagnosis, principles and rationale of therapy and treatment of drug sensitive and drug resistant tuberculosis including the shorter regimen and regrouping of drugs are important considerations of our review., (Copyright © 2019 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Background: Currently available injectable agents are inadequate to address the high drug-resistant tuberculosis (DR-TB) burden in China. Regimens including the oral agent bedaquiline have been shown to be efficacious and safe, leading to its incorporation into multiple national TB treatment programs. This analysis evaluated the impact of increased adoption of bedaquiline-containing regimens on the DR-TB burden in China., Methods: A state-transition model was developed that permits movement and interaction between susceptible, latent, and active TB disease states, while distinguishing between drug-sensitive (DS) and DR-TB. Model inputs were obtained from the published literature or derived such that model metrics approximated those published by the WHO. Expected improvements in infrastructure were built into the model to forecast the epidemiology of DR-TB in China through 2040 in the absence of bedaquiline (baseline forecast). The impact of higher utilization of bedaquiline-containing regimens (85% peak share) was then assessed in two scenarios that differed with regard to treatment success rates of the regimens: 61% (reflecting findings of clinical trials) and 80% (reflecting data from observational studies), versus the 44% success rate associated with standard-of-care treatment., Results: In the baseline scenario, the model predicted increases in annual incidence of DR-TB by 6-8% during each five-year period between 2020 and 2040, with an increase of 30% over the entire study duration. Adoption of bedaquiline-based regimens limits the incidence increases to only 1-3% in each five-year period and to 8% over the study duration in the 61% success rate scenario. Incidence declines by 1-6% during each five-year period and by 12% over the study duration in the 80% success rate scenario. Similar effects on DR-TB prevalence (4-5% increase in baseline, 0-7% decline in scenario 1, and 4-19% decline in scenario 2) and mortality (5-7% increase in baseline, 0-16% decline in scenario 1, and 6-40% decline in scenario 2) were seen following bedaquiline adoption., Conclusions: Incorporation of bedaquiline into DR-TB treatment regimens will significantly reduce the DR-TB burden in China, helping to counter the expected increase in burden in the absence of bedaquiline. The study will provide valuable information to public health policy planners.

Objectives: Drug-resistant tuberculosis (DR-TB) is a major challenge to national TB control programmes in developing countries. In the Pakistan province of Punjab, the extent and development of DR-TB is not well known. The current study was therefore conducted to assess the incidence and predictors of DR-TB in Punjab Province., Methods: Drug susceptibility testing was performed for 863 confirmed culture-positive Mycobacterium tuberculosis isolates using the proportion method. Patients were enrolled in the Programmatic Management of Drug-Resistant TB Unit of Gulab Devi Chest Hospital (Lahore, Pakistan) from August 2011 to September 2013. Data analysis was performed using IBS SPSS Statistics v.20. Multivariate logistic regression analysis was performed to assess risk factors for DR-TB., Results: The rate of resistance to at least one drug (i.e. DR-TB) was 35.0% (302/863) and the rate of multidrug-resistant TB (MDR-TB) was 30.0% (259/863). Among DR-TB cases, the number of females was relatively higher (167/302; 55.3%) compared with males. The majority of DR-TB patients resided in a rural area (229/302; 75.8%). Significant predictors of DR-TB were age 18-45 years, previous TB treatment, rural residence, being a housewife, being married, duration of sickness >1year and unemployment., Conclusion: The problem of DR-TB in Pakistan is significant. The strongest risk factors were young age and previous anti-TB treatment. Being married, being a housewife, rural residence and unemployment were also risk factors, culminating in an urgent need for effective control, early diagnosis and treatment policies for DR-TB., (Copyright © 2019 International Society for Antimicrobial Chemotherapy. Published by Elsevier Ltd. All rights reserved.)

Background: Adverse events (AEs) are common during treatment of drug-resistant tuberculosis (DR-TB). Little is known about the health-related quality of life (HRQoL) of patients receiving treatment for DR-TB or the effect of AEs on HRQoL., Methods: We conducted a cross-sectional study among adult patients with laboratory-confirmed rifampicin resistant tuberculosis (TB) on DR-TB treatment at a public-sector outpatient DR-TB clinic in Johannesburg, South Africa between 02/2015-01/2018. Data on HRQoL using the Medical Outcomes Short Form-36 (SF-36) questionnaire and self-reported AEs were collected by trained interviewers through face-to-face interviews. We report averages for the eight major domains and mental (MCS) and physical health (PCS) component summary scores, stratified by whether AEs were reported in the last four weeks. For comparative purposes, we enrolled two other patient groups and included data on a separate group of healthy adults., Results: We enrolled 149 DR-TB patients (median age 36 years IQR 29-43, 55% male, 77.9% HIV-positive, 81% on ART, 61.8% on a standard long-course regimen and 44.3% on DR-TB treatment for less than 6 months). 58/149 (38.9%) patients reported a total of 122 AEs in the preceding 4 weeks, of these the most common were joint pain (n = 22), peripheral neuropathy (n = 16), hearing loss (n = 15), nausea and vomiting (n = 12) and dizziness or vertigo (n = 11). SF-36 domains and summary scores (MCS and PCS) were lower in those who reported an AE compared to those who did not, and both were lower than healthy adults. Compared to those who did not report an AE, patients who reported AEs were more likely to have a low MCS (aRR 2.24 95% CI 1.53-3.27) and PCS (aRR 1.52 95% CI 1.07-2.18) summary score. HRQoL was lower among those on DR-TB treatment for 6 months or less., Conclusion: Results show that DR-TB had a substantial impact on patients' quality of life, but that AEs during the early months on treatment may be responsible for reducing HRQoL even further. Our findings highlight the negative effects of injectable agents on HRQoL. Patients require an integrative patient-centered approach to deal with DR-TB and HIV and the potential overlapping toxicities which may be worsened by concurrent treatment.

Background: South Africa has high burdens of HIV, TB and drug-resistant TB (DR-TB, rifampicin-resistance). Treatment outcome data for HIV-infected versus uninfected patients is limited. We assessed the impact of HIV and other factors on DR-TB treatment success, time to culture conversion, loss-from-treatment and overall mortality after second-line treatment initiation., Methods: A retrospective cohort analysis was conducted for patients initiated on DR-TB treatment from 2008 to 2012, within a community-based, decentralised programme in Khayelitsha, South Africa., Results: Among 853 confirmed DR-TB patients initiating second-line treatment, 605 (70.9%) were HIV infected. HIV status did not impact on time to sputum culture conversion nor did it impact treatment success; 48.1% (259/539) and 45.9% (100/218), respectively (p=0.59). In a multivariate model, HIV was not associated with treatment success. Death during treatment was higher among HIV-infected patients, but overall mortality was not significantly higher. HIV-infected patients with CD4 <=100 cells/ml were significantly more likely to die after starting treatment., Conclusions: Response to DR-TB treatment did not differ with HIV infection in a programmatic setting with access to antiretroviral treatment (ART). Earlier ART initiation at a primary care level could reduce mortality among HIV-infected patients presenting with low CD4 counts., (© The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Drug-resistant tuberculosis (DR-TB) has become a serious cause of concern both on a global scale and in South Africa. It is associated with a lower successful treatment rate, thus creating a hurdle in achieving good treatment outcomes for patients. Aim: The aim of this study was to compare the efficacy of the drug kanamycin, an injectable aminoglycoside, to bedaquiline, a newer oral drug used to treat DR-TB. Methods: PubMed and Google Scholar, both of which are online databases, were extensively searched using the necessary keywords so that studies that were relevant to the scoping review were retrieved. A data-charting list was developed to extract the needed data for this scoping review. Results: The main findings of the scoping review showed that bedaquiline was highly efficacious in the treatment of DR-TB, and that it was a valuable addition in the treatment of DR-TB. The findings of the study also showed that kanamycin does not have good efficacy against DR-TB. and its use extends the treatment of DR-TB. Conclusion: It stands to reason that bedaquiline replaces kanamycin in the DR-TB drug regimen as it was shown to be more efficacious and patients experienced better treatment outcomes in a shorter period of time. There were also fewer adverse effects associated with bedaquiline as compared to kanamycin. Contribution: Bedaquiline-based DR-TB therapy is more efficacious than aminoglycoside-based regimens which include kanamycin. [ABSTRACT FROM AUTHOR]