Multidrug-resistant Tuberculosis Treatment Outcomes Research Articles

Bedaquiline Delivery Innovations: A Review on Advancing MDR-TB Treatment Strategies

Abstract: Multidrug-resistant tuberculosis (MDR-TB) poses a persistent challenge to global health, necessitating continuous efforts to enhance treatment efficacy. Bedaquiline, a cornerstone in MDR-TB management, presents biopharmaceutical challenges that impact its therapeutic potential. This review provides a comprehensive analysis of recent innovations in drug delivery strategies designed to optimize Bedaquiline's efficacy and improve MDR-TB treatment outcomes. Through a systematic examination of various delivery systems, including nanotechnology and formulation advancements, we explore their potential in addressing drug solubility and bioavailability challenges. Emphasizing the integration of Quality by Design (QbD) principles, this review aims to present a cohesive overview of evolving Bedaquiline delivery innovations, providing valuable insights for researchers and healthcare practitioners working towards advancing MDR-TB treatment strategies.

Multidrug-resistant tuberculosis treatment outcomes and associated factors at Yirgalem General Hospital, Sidama Region, South Ethiopia: a retrospective cohort study

BackgroundThe spread of multidrug-resistant tuberculosis (MDR-TB) poses a significant challenge to TB control efforts. This study evaluated the treatment outcomes and associated factors among patients receiving treatment for MDR-TB in southern Ethiopia.MethodsA retrospective follow-up study covering ten years, from 2014 to 2023, analyzed the records of confirmed cases of pulmonary TB admitted to Yirgalem General Hospital, an MDR-TB treatment initiation center in the Sidama Region. To compare the successful treatment outcomes across the years, a chi-square test of independence was conducted. Bivariate and multivariable logistic regression models were used to identify factors associated with treatment outcomes for MDR-TB.ResultsOut of 276 confirmed MDR-TB cases, 4(1.4%) were diagnosed with resistance to second-line drugs (SLDs). Overall, 138 patients achieved favourable treatment outcomes, resulting in a treatment success rate of 50.0% [95% CI 44.1–55.9%]. Among these 138 patients, 105(76.1%, 95 CI 68.7–83.5%) were cured, while 33(23.9%, 95 CI 16.5–31.3%) completed their treatment. The successful treatment outcomes varied significantly across the years, ranging from 3.6% in 2020 to 90% in 2021. The analysis indicated a statistically significant difference in treatment outcomes when considering data from 2014 to 2023 (χ2 = 44.539, p = 0.001). The proportion of patients with deaths, lost-to-follow-up (LTFU), treatment failures and not evaluated were 7.9% [95% CI 4.8–11.2%], 10.9% [95% CI 7.2–14.6%), 2.2% [95% CI 1.1–3.3%), and 28.9% [95% CI 23.7–34.2%] respectively. Individuals with a positive HIV status had significantly lower odds of a favorable treatment outcome [AOR = 0.628, 95% CI (0.479–0.824), p = 0.018]. Similarly, patients with a BMI of less than 18 are more likely to have unfavorable treatment outcomes compared to those with a BMI of 18 or higher [AOR = 2.353, 95% CI 1.404–3.942, p < 0.001].ConclusionThe study revealed a concerning 1.4% prevalence of additional resistance to SLDs. The 50% rate of unfavorable treatment among MDR-TB cases exceeds the target set by the WHO. A significant number of patients (10.9%) were LTFU, and the 28.9% categorized as ‘not evaluated’ is also concerning. Enhanced strategic interventions are needed to reduce such cases, and factors associated with poor treatment outcomes should receive greater attention. Future prospective studies can further explore the factors influencing improved treatment success.

Drug Exposure and Treatment Outcomes in Patients With Multidrug-Resistant Tuberculosis and Diabetes Mellitus: A Multicenter Prospective Cohort Study From China.

The management of multidrug-resistant tuberculosis (MDR-TB) remains challenging. Treatment outcome is influenced by multiple factors; the specific roles of diabetes and glycemic control remain uncertain. This study aims to assess the impact of glycemic control on drug exposure, to investigate the association between drug exposure and treatment outcomes, and to identify clinically significant thresholds predictive of treatment outcome, among patients with diabetes. This multicenter prospective cohort study involved patients with confirmed MDR-TB and diabetes. Drug exposure level was estimated by noncompartmental analysis. The minimum inhibitory concentrations (MICs) were determined for the individual Mycobacterium tuberculosis isolates. The influence of poor glycemic control (glycated hemoglobin ≥7%) on drug exposure and the associations between drug exposure and treatment outcome were evaluated by univariate and multivariate analysis. Classification and regression tree analysis was used to identify the drug exposure/susceptibility thresholds. Among the 131 diabetic participants, 43 (32.8%) exhibited poor glycemic control. Poor glycemic control was independently associated with decreased exposure to moxifloxacin, linezolid, bedaquiline, and cycloserine, but not clofazimine. Additionally, a higher ratio of drug exposure to susceptibility was found to be associated with a favorable MDR-TB treatment outcome. Thresholds predictive of 6-month culture conversion and favorable outcome were bedaquiline area under the concentration-time curve (AUC)/MIC ≥245 and moxifloxacin AUC/MIC ≥67, demonstrating predictive accuracy in patients, regardless of their glycemic control status. Glycemic control and optimal TB drug exposure are associated with improved treatment outcomes. This dual management strategy should be further validated in randomized controlled trials of patients with MDR-TB and diabetes.

Factors associated with unfavorable treatment outcomes among multidrug-resistant tuberculosis patients, Sierra Leone: a cross-sectional secondary data analysis

BackgroundGlobally, multidrug-resistant tuberculosis (MDR-TB) is a major public health problem. The tuberculosis rate in Sierra Leone is 298 per 100,000 people, and Sierra Leone is considered a country with a high burden of tuberculosis. In Sierra Leone, there are few studies on the outcomes of MDR-TB treatment, especially those exacerbated by COVID-19. We identified factors associated with unfavorable treatment outcomes among people with MDR-TB in Sierra Leone.MethodsWe conducted a cross-sectional study to analyze hospital-based MDR-TB data from 2017 to 2021. Demographic, clinical, and treatment outcome data were extracted from the main MDR-TB referral hospital database. We defined unfavorable outcomes as patients who died, were lost to follow-up, or defaulted. We calculated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to identify predictors of the outcomes of MDR-TB treatment.ResultsBetween 2017 and 2021, 628 people with MDR-TB were reported at Lakka Hospital; 441 (71%) were male, with a median age of 25 years (interquartile ranges: 17–34). Clinically, 21% of the 628 MDR-TB patients were HIV positive, and 413 were underweight (66%). 70% (440) of MDR-TB patients received tuberculosis treatment. The majority of patients, 457 (73%), were treated with a short treatment regimen, and 126 (20%) experienced unfavorable outcomes. Age 45 years or younger (aOR = 5.08; CI:1.87–13.82), 21–45 years (aOR = 2.22; CI:140–3.54), tuberculosis retreatment (aOR = 3.23; CI:1.82–5.73), age group, HIV status (aOR = 2.16; CI:1.33–3.53), and malnourishment status (aOR = 1.79; CI:1.12–2.86) were significantly associated with unfavorable treatment outcomes for DR-TB patients.ConclusionThis analysis revealed a high proportion of unfavorable treatment outcomes among MDR-TB patients in Sierra Leone. Malnourishment, TB retreatment, HIV coinfection, and age 45 years or younger were associated with unfavorable outcomes of MDR-TB treatment. Increasing patients’ awareness, mainly among young people, heightens treatment adherence and HIV monitoring by measuring the amount of HIV in patient blood, which can reduce adverse treatment outcomes in Sierra Leone and other sub-Saharan African countries.

Comparison of short term and long term multidrug resistant tuberculosis treatment outcomes in tertiary care settings

IntroductionTuberculosis is a contagious and communicable disease while drug resistant tuberculosis is difficult to treat and requires long duration. Various strategies are focused to treat the drug resistant tuberculosis focusing lesser side effects and shorter duration of treatment. ObjectiveTo compare treatment outcomes between short-term and long-term regimens among patients registered at a tertiary care hospital's Programmatic Management of Drug-Resistant TB (PMDT) site in Pakistan. MethodsA comparative prospective cohort study was conducted at IMBB, The University of Lahore, in collaboration with the Health Research Institute (HRI) TB Research Centre at King Edward Medical University/Mayo Hospital, Lahore. The study included a sample size of 136 patients, with 68 patients in each treatment regimen (long-term and short-term). Adult pulmonary MDR TB patients seeking treatment from the facility were included based on predefined criteria. Data was collected using a pre-designed questionnaire after obtaining ethical approval and informed consent. The rates of patients' cure, treatment completed, treatment failure and death were calculated. ResultsA total of 131 patients were successfully followed up and included in the final analysis. Of these, 66 patients were in the long-term treatment group and 65 patients were in the short-term treatment group. The cure rate was 74.8 %, with 98 patients successfully cured, and 13.8 % of patients completed their treatment successfully. In the long-term treatment group, the cure rate was 75.6 %, with a treatment failure rate of 6.2 %. In the short-term treatment group, the cure rate was 73.8 %, with a treatment failure rate of 6.1 %. The death rate was 4.5 % in the short-term treatment group and 6.2 % in the long-term treatment group. However, these differences in treatment outcomes were statistically insignificant (p-values > 0.05). The newer drugs, bedaquiline and delamanid, did not show significant improvements in the treatment of multidrug-resistant TB patients. Side effects at completion of treatment remained to be significantly lesser (p < 0.05) among short term treatment group as compared to long term treatment group. ConclusionThe findings suggest that short-term treatment regimens are equally effective as long-term treatment regimens, with the added benefit of presenting fewer side effects.

Impacts of body weight change on treatment outcomes in patients with multidrug-resistant tuberculosis in Northwest Ethiopia

Measuring body weight during therapy has received insufficient attention in poor resource settings like Ethiopia. We aimed to investigate the association between weight change during therapy and treatment outcomes among patients with multidrug-resistant tuberculosis (MDR-TB) in northwest Ethiopia. This retrospective cohort study analysed data from patients with MDR-TB admitted between May 2015 to February 2022 at four treatment facilities in Northwest Ethiopia. We used the joint model (JM) to determine the association between weight change during therapy and treatment outcomes for patients with MDR-TB. A total of 419 patients with MDR-TB were included in the analysis. Of these, 265 (63.3%) were male, and 255 (60.9%) were undernourished. Weight increase over time was associated with a decrease in unsuccessful treatment outcomes (adjusted hazard ratio (AHR): 0.96, 95% CI: 0.94 to 0.98). In addition, patients with undernutrition (AHR: 1.72, 95% CI: 1.10 to 2.97), HIV (AHR:1.79, 95% CI: 1.04 to 3.06), and clinical complications such as pneumothorax (AHR: 1.66, 95% CI: 1.03 to 2.67) were associated with unsuccessful treatment outcomes. The JM showed a significant inverse association between weight gain and unsuccessful MDR-TB treatment outcomes. Therefore, weight gain may be used as a surrogate marker for good TB treatment response in Ethiopia.

Relationship between HIV viral suppression and multidrug resistant tuberculosis treatment outcomes.

The impact of HIV viral suppression on multidrug resistant tuberculosis (MDR-TB) treatment outcomes among people with HIV (PWH) has not been clearly established. Using secondary data from a cluster-randomized clinical trial among people with MDR-TB in South Africa, we examined the effects of HIV viral suppression at MDR-TB treatment initiation and throughout treatment on MDR-TB outcomes among PWH using multinomial regression. This analysis included 1479 PWH. Viral suppression (457, 30.9%), detectable viral load (524, 35.4%), or unknown viral load (498, 33.7%) at MDR-TB treatment initiation were almost evenly distributed. Having a detectable HIV viral load at MDR-TB treatment initiation significantly increased risk of death compared to those virally suppressed (relative risk ratio [RRR] 2.12, 95% CI 1.11-4.07). Among 673 (45.5%) PWH with a known viral load at MDR-TB outcome, 194 (28.8%) maintained suppression, 267 (39.7%) became suppressed, 94 (14.0%) became detectable, and 118 (17.5%) were never suppressed. Those who became detectable (RRR 11.50, 95% CI 1.98-66.65) or were never suppressed (RRR 9.28, 95% CI 1.53-56.61) were at significantly increased risk of death (RRR 6.37, 95% CI 1.58-25.70), treatment failure (RRR 4.54, 95% CI 1.35-15.24), and loss to follow-up (RRR 7.00, 95% CI 2.83-17.31; RRR 2.97, 95% CI 1.02-8.61) compared to those who maintained viral suppression. Lack of viral suppression at MDR-TB treatment initiation and failure to achieve or maintain viral suppression during MDR-TB treatment drives differences in MDR-TB outcomes. Early intervention to support access and adherence to antiretroviral therapy among PWH should be prioritized to improve MDR-TB treatment outcomes.

Treatment Outcomes in Multidrug-Resistant Tuberculosis During Pregnancy.

Treatment Outcomes in Multidrug-Resistant Tuberculosis During Pregnancy.

Successful Multidrug-Resistant Tuberculosis Treatment Without HIV Viral Suppression: A Missed Opportunity.

Coinfection with multidrug-resistant tuberculosis (MDR-TB) and HIV is common, but few published studies examine how undergoing MDR-TB treatment affects HIV disease indicators. Using data from a nested, retrospective cohort of people with HIV (PWH) and successful MDR-TB treatment outcomes, we built multivariable regression models to explore correlates of HIV viral suppression at MDR-TB treatment completion. Among 531 PWH successfully treated for MDR-TB, mean age was 37.4 years (SD 10.2, interquartile range 30-43), 270 (50.8%) were male, 395 (74.4%) were virally suppressed at MDR-TB outcome, and 259 (48.8%) took bedaquiline. Older age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI]: 1.01 to 1.06) increased odds of viral suppression, while having a prior TB episode (aOR 0.45, 95% CI: 0.31 to 0.64), having a detectable viral load at MDR-TB treatment initiation (aOR 0.17, 95% CI: 0.09 to 0.30), living in a township (aOR 0.49, 95% CI: 0.28 to 0.87), and being changed from efavirenz-based antiretroviral therapy (ART) to a protease inhibitor due to bedaquiline usage (aOR 0.19, 95% CI: 0.04 to 0.82) or not having an ART change while on bedaquiline (aOR 0.29, 95% CI: 0.11 to 0.75) lowered odds of viral suppression. Changing from efavirenz to nevirapine due to bedaquiline usage did not significantly affect odds of viral suppression (aOR 0.41, 95% CI: 0.16 to 1.04). Increased pill burden and adverse treatment effects did not significantly affect HIV viral suppression while switching ART to a protease inhibitor to accommodate bedaquiline or not changing ART while taking bedaquiline did, suggesting that PWH and MDR-TB may benefit from additional support if they must switch ART.

Effectiveness of Community-Based Multidrug-Resistant Tuberculosis Treatment in Nigeria: A Retrospective Cohort Study

Growing multidrug-resistant tuberculosis (MDR-TB) worldwide and new effective and affordable treatment modalities required exploring options such as the community model of MDR-TB treatment (CM), as introduced in Nigeria.To determine the most effective care model by comparing MDR-TB treatment outcomes at community-based sites with the hospital-based model of care in Nigeria.Treatment outcomes data were retrospectively accessed from the medical record of 423 MDR-TB patients to evaluate the effectiveness of HM and CM based on WHO criteria. Treatment success” is defined as the sum of cure and treatment completion. “Cure” is the “treatment completion” with at least three negative cultures taken at least 30 days apart after the intensive phase in the absence of “treatment failure. Predictors of treatment outcomes were also assessed on multivariate analysis. 423 patients (85% of the targeted sampling data) were available for analysis, of whom 272 (63.4%) had a conventional regimen, and 143 (33.8%) had a shorter treatment regimen. There is no significant difference in treatment outcomes between CM and HM; patients achieve similar treatment success in all models, 65.5% with HM compared to 68% at the CM (p = 0.608). Treatment failure was (4.1% versus 5.1%) in the HM versus CM, respectively; (p = 0.704). Death occurred in 20.9% of participants in the hospital model and 17.5% in the community model, and rates of Loss to follow-up were similar 9.5% HM vs 9.5% CM; (p = 0.704). On multivariate analysis, adjusting for age, HIV, sex, patient type, TB treatment history, resistance pattern, model of care and regimens, there was no change in treatment outcomes if patients were treated at the CM vs HM (adjusted odds ratio [aOR] 0.92; 95% CI 0.59 – 1.46, p = 0.735). MDR-TB patients with unknown HIV status (not on ART) were nine times more likely to have unsuccessful treatment outcomes compared with HIV-negative respondents (adjusted odds ratio [aOR] 8.83; 95% CI 1.79 – 43.60, p = 0.007). Similarly, HIV-positive respondents were 1.3 times more likely to have unsuccessful outcomes than HIV-negative (adjusted odds ratio [aOR] 1.26; 95% CI 0.71–2.26, p = 0.429, but the difference is not statistically significant. This retrospective study found that the community-based model is equally effective as care in a centralised hospital, based on similar treatment success rates, comparable default and death rates with hospital care and shorter time to treatment initiation at the community-based centres.

Assessment of Treatment Outcomes of Multidrug-Resistant Tuberculosis in Bangladeshi Population: A Retrospective Cohort Study

Introduction: Every year millions of people fall sick with Tuberculosis (TB). Multidrug-resistant tuberculosis (MDR-TB) has a life threatening public health crisis globally. Objective: To determine the successful treatment outcomes of MDR-TB in Bangladeshi population. Methods: This retrospective cohort study was conducted at the National Institute of Diseases of the Chest and Hospital (NIDCH) Mohakhali, Dhaka, on 224 patients enrolled within July 2014 to June 2015. Data were collected by face-to-face interview and reviewing medical records. Results: A total of 224 MDR-TB patients’ histories were studied, among them male and female were 71% and 29% respectively. The average age was 37.6± 13.7 years. Of the total MDR-TB patients, 49(21.9%) were successfully treated, 124 (55.4%) had completed, 3(1.3%) had treatment failure, 5(2.2%) were lost to follow-up, 1(0.4%) was XDR-TB and 29 (12.9%) died. This study also found out that the patient with advanced age (≥55;p&lt;0.001), living in rural areas (p&lt;0.01), history of missing dose(p&lt;0.001) and co-morbidity after treatment (p&lt;0.05) were significantly associated with poor treatment outcomes of MDR-TB. Conclusion: The study concluded that the successful treatment outcomes were 77.2% and the mortality rate was 12.9% of MDRTB patients. Living in rural areas and missing dose were significantly associated with poor treatment outcomes. So, the study demonstrated that it is necessary to ensure the completion of whole treatment course to manage TB patients effectively in order to prevent MDR-TB. JAFMC Bangladesh. Vol 18, No 1 (June) 2022: 57-60

Treatment Outcomes and Risk Factors of Multidrug-Resistant Tuberculosis Patients in Xi'an China, a Retrospective Cohort Study.

BackgroundLong-term regimens are widely used for multidrug-resistant tuberculosis (MDR-TB) in North-West China; however, risk factors associated with the treatment outcomes are not well known.MethodsThis was a retrospective cohort study of MDR-TB patients treated with longer regimen in Xi’an from 2017 to 2019. Risk factors associated with the treatment outcome were analyzed using multiple logistic regression.ResultsOf the 446 patients with MDR-TB included, 215 were cured, 84 completed treatment, 23 failed treatment, 108 were lost to follow-up, and 16 died. Unfavorable outcome risk factors were age >40 years (OR = 3.25, 95% CI = 2.12–4.98), male sex (OR = 2.53, 95% CI = 1.52–4.22), and re-treated tuberculosis (OR = 1.70, 95% CI = 1.11–2.61), whereas poor treatment outcome risk factors were age >40 years (OR = 5.51, 95% CI = 2.52–12.07), fluoroquinolones not used in the regimen (OR = 3.31, 95% CI = 1.45–7.51), and smear-positive (OR = 4.0, 95% CI = 1.47–10.8).ConclusionIn Xi’an, MDR-TB treatments with long-term regimens had low success rates, and age, sex, and tuberculosis treatment history were risk factors of MDR-TB treatment outcomes.

Treatment outcomes and associated factors among patients with multidrug-resistant tuberculosis in Ashanti Region, Ghana: a retrospective, cross-sectional study

ObjectiveAlthough several studies have assessed treatment outcomes of drug-susceptible tuberculosis (TB) in Ghana, very little has been done in the area of multidrug-resistant TB (MDR-TB). The aim of this study...

Bedaquiline Adherence Measured by Electronic Dose Monitoring Predicts Clinical Outcomes in the Treatment of Patients With Multidrug-Resistant Tuberculosis and HIV/AIDS.

Novel regimens have revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment; however, medication adherence remains challenging and poorly characterized. We hypothesized that bedaquiline adherence, measured using electronic dose monitoring, would predict MDR-TB treatment outcomes. This is a prospective cohort study conducted in KwaZulu-Natal, South Africa. Adults with MDR-TB and HIV initiating bedaquiline and on antiretroviral therapy (ART) were eligible. Separate electronic dose monitoring devices measured bedaquiline and ART adherence through 6 months, calculated as observed versus expected doses. Whole-genome sequencing was performed to identify bedaquiline resistance-associated variants. From November 2016 through February 2018, 199 participants with MDR-TB and HIV were enrolled and followed up through treatment completion (median 17.2 months interquartile range 12.2-19.6). The median bedaquiline adherence was higher than ART adherence (97 vs. 89%, P < 0.001) but correlated (r2 = 0.68, P < 0.001). High bedaquiline adherence (≥90%) compared with lower adherence was associated with improved end of treatment successful outcome (83.4% vs. 46.3%, P < 0.001), decreased mortality (11.0% vs. 29.6% P = 0.004), and improved retention in care through end of treatment (94.5% vs. 79.6% P = 0.002). Modeling identified a highly significant but linear association between bedaquiline adherence and outcome. On multivariable analysis, bedaquiline adherence was independently associated with mortality and outcome. Bedaquiline resistance-associated variants were seen in 12% (7/57) of sequenced isolates (7% baseline, 5% emergent) with only 28.6% experiencing successful treatment outcome. Bedaquiline adherence through 6 months independently predicted end of MDR-TB treatment outcome, but a specific bedaquiline adherence threshold was not identified. Interventions to optimize bedaquiline adherence are urgently needed to improve MDR-TB HIV treatment outcomes.

Adjunctive Zoledronate + IL-2 administrations enhance anti-tuberculosis Vγ2Vδ2 T-effector populations, and improve treatment outcome of multidrug-resistant tuberculosis1

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) is a refractory disease with high mortality rate due to no or few choices of antibiotics. Adjunctive immunotherapy may help improve treatment outcome of MDR-TB. Our decade-long studies demonstrated that phosphoantigen-specific Vγ2Vδ2 T cells play protective roles in immunity against TB. Here, we hypothesized that enhancing protective Vγ2Vδ2 T-effector cells could improve treatment outcome of MDR-TB. To address this, we employed clinically approved drugs Zoledronate (ZOL) and IL-2 to induce anti-TB Vγ2Vδ2 T-effector cells as adjunctive immunotherapy against MDR-TB infection of macaques. We found that adjunctive ZOL/IL-2 administrations during TB drugs treatment of MDR-TB-infected macaques significantly expanded Vγ2Vδ2 T cells and enhanced/sustained Vγ2Vδ2 T-effector subpopulation producing anti-TB cytokines until week 21. ZOL/IL-2 administrations, while expanding Vγ2Vδ2 T cells, significantly increased/sustained numbers of circulating CD4+ Th1 and CD8+ Th1-like effector populations, with some γδ T- or αβ T-effector populations trafficking to airway at week 3 until week 19 or 21 after MDR-TB infection. Adjunctive ZOL/IL-2 administrations after MDR-TB infection led to lower bacterial burdens in lungs than TB drugs alone, IL-2 alone or saline controls, and resulted in milder MDR-TB pathology/lesions. Thus, adjunctive Zoledronate + IL-2 administrations can enhance anti-TB Vγ2Vδ2 T- and αβ T-effector populations, and improve treatment outcome of MDR-TB.

Multidrug-Resistant Tuberculosis Treatment Outcome and Associated Factors at the University of Gondar Comprehensive Specialized Hospital: A Ten-Year Retrospective Study.

BackgroundMultidrug-resistant tuberculosis (MDR-TB) remains a public health crisis and a health security threat worldwide. Poor public health infrastructure, inefficient infection control and mismanagement of TB treatment are among the reasons for the continuous emergence and spread of drug-resistant TB (DR-TB). The final treatment outcome is the most direct measurement of TB control programs. Therefore, this study sought to determine the proportions and predictors of TB treatment outcomes among MDR/RR-TB treated patients.MethodsA 10-year, 2011 to 2021, hospital-based retrospective cohort study was conducted at the University of Gondar Comprehensive Specialized Hospital. The records of 408 MDR-TB patients, 389 with treatment outcome and 19 on treatment, were collected using a structured checklist.ResultsA total of 389 patients with a recorded MDR/RR-TB treatment outcome were included. The treatment success rate was 77.12%, with 58.35% cured and 18.76% treatment completed. The proportion of death rate, treatment default loss to follow-up, treatment failure, and unknown treatment outcome was 9.25%, 6.94%, 3.1%, and 3.6%, respectively. Regarding the patient category, the most successful treatment outcome (83.5%) came from patients diagnosed with relapse cases, followed by new cases (81.8%). An unsuccessful treatment outcome was significantly associated with patients aged >44 years (AOR, 3.3, 95% CI = 1.55–6.99).Conclusion and RecommendationsThis study indicated that nearly 23% of MDR/RR-TB patients had unsuccessful treatment outcomes and being older was significantly correlated with these outcomes. For better outcomes, it is recommended to strengthen combined treatment adherence interventions and evaluate treatment regimens and administration options. A prospective cohort study may be required to investigate the full range of potential causes of unfavorable outcomes.

Factors associated with treatment outcome of multidrug-resistant tuberculosis patients co-infected with human immunodeficiency virus in a Drug Resistant Tuberculosis Centre

Background: Tuberculosis is one of the major public health problem, further complicated by the relentless spread of human immunodeficiency virus (HIV). The incidence of drug resistant TB among HIV patients is now increasing. Treatment outcomes in multidrug-resistant tuberculosis (MDR-TB) patients co-infected with HIV is poorly documented. Objectives: Assessed the treatment outcome of MDR-TB co-infected with HIV treated under programmatic management of drug resistant tuberculosis. Methods: The study was conducted in Department of Respiratory Medicine, Princess Krishnajammanni Tuberculosis and Chest Diseases (PK TB &amp; CD) Hospital, Mysore Medical College and Research Institute (MMCRI), Mysore. It is a retrospective study done on patients who were admitted in DRTB center of PK TB &amp; CD hospital, Mysore for initiation of treatment from January 2013 to December 2019. Results: Among the 63 patients studied, 26 patients (41.3%) had a favorable outcome with cure and treatment completed. 25 patients (39.7%) had an unfavorable outcome with death, 9 patients (14.3%) defaulted during the treatment and 2 patients (3.2%) had failure of therapy. Conclusion: Early recognition and treatment of HIV with ART and the clinical stage of the disease during presentation affect the treatment outcome in patients with MDR-TB. Keywords: tuberculosis; HIV; outcome; multidrug resistance; ART

Predictors of treatment outcomes among patients with multidrug-resistant tuberculosis in Vietnam: a retrospective cohort study

BackgroundImproving treatment outcomes for multidrug-resistant tuberculosis (MDR-TB) is a leading priority for global TB control. This retrospective cohort study evaluated the factors associated with treatment success among patients treated for MDR-TB in two provinces in Vietnam.MethodsTreatment outcomes were evaluated for adult patients treated in Hanoi and Thanh Hoa provinces between 2014 and 2016. The primary outcome was the proportion of patients with treatment success, defined as cure or treatment completion. Logistic regression analysis was used to evaluate the relationship between patient clinical and microbiological characteristics and treatment success.ResultsTreatment outcomes were reported in 612 of 662 patients; of these, 401 (65.5)% were successfully treated. The odds of treatment success were lower for male patients (aOR 0.56, 95% CI 0.34–0.90), for people living with HIV (aOR 0.44, 95% CI 0.20–1.00), and for patients treated for extensive antibiotic resistance (pre-XDR-/XDT-TB) (aOR 0.53, 95% CI 0.29–0.97), compared with others. Patients who achieved culture conversion in the first 4 months of treatment had increased odds (aOR 2.93, 95% CI 1.33–6.45) of treatment success. In addition, loss to follow-up was less common among patients covered by social health insurance compared to those who paid for treatment out-of-pocket (aOR 0.55, 95% CI 0.32–0.95).ConclusionsAmong patients with MDR-TB, males, people living with HIV, and those with more extensive antibiotic resistance at diagnosis are at greatest risk of an unsuccessful treatment outcome. Efforts to optimise the management of co-morbidities (such as HIV), ensure rapid bacteriological conversion, and provide financial support for patients promise to improve treatment outcomes.

Drug exposure and susceptibility of second-line drugs correlate with treatment response in patients with multidrug-resistant tuberculosis: a multicentre prospective cohort study in China.

BackgroundUnderstanding the impact of drug exposure and susceptibility on treatment response of multidrug-resistant tuberculosis (MDR-TB) will help to optimise treatment. This study aimed to investigate the association between drug exposure, susceptibility and response to MDR-TB treatment.MethodsDrug exposure and susceptibility for second-line drugs were measured for patients with MDR-TB. Multivariate analysis was applied to investigate the impact of drug exposure and susceptibility on sputum culture conversion and treatment outcome. Probability of target attainment was evaluated. Random Forest and CART (Classification and Regression Tree) analysis was used to identify key predictors and their clinical targets among patients on World Health Organization-recommended regimens.ResultsDrug exposure and corresponding susceptibility were available for 197 patients with MDR-TB. The probability of target attainment was highly variable, ranging from 0% for ethambutol to 97% for linezolid, while patients with fluoroquinolones above targets had a higher probability of 2-month culture conversion (56.3% versus 28.6%; adjusted OR 2.91, 95% CI 1.42–5.94) and favourable outcome (88.8% versus 68.8%; adjusted OR 2.89, 95% CI 1.16–7.17). Higher exposure values of fluoroquinolones, linezolid and pyrazinamide were associated with earlier sputum culture conversion. CART analysis selected moxifloxacin area under the drug concentration–time curve/minimum inhibitory concentration (AUC0–24h/MIC) of 231 and linezolid AUC0–24h/MIC of 287 as best predictors for 6-month culture conversion in patients receiving identical Group A-based regimens. These associations were confirmed in multivariate analysis.ConclusionsOur findings indicate that target attainment of TB drugs is associated with response to treatment. The CART-derived thresholds may serve as targets for early dose adjustment in a future randomised controlled study to improve MDR-TB treatment outcome.

Clinical characteristics and treatment outcome of multidrug-resistant pulmonary tuberculosis complicated with diabetes mellitus

Objective To compare the clinical characteristics and treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients with and without diabetes melitus (DM), and we improve clinicians’ understanding of drug-resistant pulmonary tuberculosis complicated with diabetes. Methods A total of 322 patients with MDR-TB in Xi’an Chest Hospital were selected as the research subjects, including 60 patients (18.6%) in the DM+ group, 262 patients (81.4%) were in the DM– group without diabetes. Age, gender, body mass index (BMI), complicated liver disease, previous treatment history, cumulative number of lung fields in imaging lesions (<3 or ≥3), clinical data such as cavity, drug resistance characteristics, treatment outcome, adverse reactions and so on were analyzed and compared between the two groups. Results 91.7% of males in DM+ group were higher than 70.2% in DM– group, and there was a statistical difference between the two groups ( P=0.001). The average age of DM+ group was (48.6±11.8) years higher than that of DM– group (34.3±14.8) years. The difference was statistically significant ( P<0.001). BMI of DM+ group was higher than that of DM– group, and there were statistically significant differences between the two groups ( P=0.003). The probability of cavities in DM+ group was higher than DM– group, and the difference between the two groups was statistically significant ( P<0.001). The probability of complicated extrapulmonary tuberculosis in DM+ group was higher than DM– group, and the difference between the two groups was statistically significant ( P=0.024). There were no significant differences between the two groups in initial retreatment, cumulative number of lung fields in imaging lesions (<3 or ≥3), and whether liver disease was complicated ( P>0.05). There was no statistical difference in the drug resistance rates of fluoroquinolones (FQS), AM (CM) and fluoroquinolones + AM (CM) between the two groups ( P>0.05). Univariate analysis of treatment outcome indicated that age, gender, initial retreatment, and the cumulative number of lung fields in the lesions had influence on the prognosis ( P<0.05). When multivariate analysis found that age and the cumulative number of lung fields in the lesions were closely related to the treatment outcome ( P<0.05). The incidence of ADR was 39.2% (85/217) in DM– group and 56.6% (30/53) in the DM+ group, and the ADR rate was higher in the DM+ group, with statistical significance between the two groups ( P=0.029). The sputum negative conversion rate of 3 months in DM+ group was 80.0% (32/40); The negative conversion rate of DM– group was 85.6%(149/174), and there was no statistical significance between the two groups ( P>0.465). Conclusion DM+ patients are mainly middle-aged and elderly males, body mass index (BMI) of DM+ patients is relatively large, and sufficient dosage of tuberculosis drugs should be given according to the body weight of patients to avoid poor therapeutic effect caused by decreased blood drug concentration. At the same time, it was found that DM+ patients were more prone to lung cavity in imaging and increased extrapulmonary tuberculosis. In clinical practice, we should be alert to the possibility of massive hemoptysis at any time and pay attention to the screening of multi-organ tuberculosis in the body. 摘要： 目的 通过对合并与不合并糖尿病(diabetes mellitus, DM)的耐多药肺结核(multi-drug resistance tuberculosis, MDR-TB)患者临床特点及治疗结局进行比较, 提髙临床医生对耐药肺结核合并糖尿病的认识。 方法 以西安市 胸科医院322例耐多药肺结核患者为研究对象, 其中合并糖尿病(DM+)组60例(18.6%);不合并糖尿病(DM–)组262例 (81.4%)。分析比较两组患者的年龄、性别、体质量指数(BMI)、合并肝病、既往治疗史、影像学病灶累计肺野数(<3或≥ 3)、有无空洞、耐药特征、治疗结局、不良反应等临床资料。 结果 DM+组男性占91.7%, 髙于DM–组70.2%, 两组间比 较差异有统计学意义( P=0.001)。DM+组平均年龄(48.6±11.8)岁髙于DM–组(34.3±14.8)岁, 两组间比较差异有统计学 意义( P<0.001)。DM+组BMI髙于DM–组, 两组间差异有统计学意义( P=0.003)。DM+组出现空洞的概率髙于DM–组, 两组间差异有统计学意义( P<0.001)。DM+组合并肺外结核的概率髙于DM–组, 两组间比较差异有统计学意义( P= 0.024)。两组在初复治、影像学病灶累积肺野数(<3或≥3)、是否合并肝病等差异均无统计学意义( P>0.05)。两组在对 氣座诺丽(Fluoroquinolones, FQs)、阿米卡星(Amikacin, Am)[卷曲霉素 Capreomycin, Cm)]、FQs+ Am(Cm)耐药率差异均 无统计学意义( P>0.05)。治疗结局单因素分析提示年龄、性别、初复治、病灶累计肺野数等因素对预后有影响( P<0.05), 多因素分析发现年龄及病灶累计肺野数与治疗结局密切相关( P<0.05)。DM–组不良反应发生率39.2%(85/217);DM+组不良反应发生率56.6%(30/53), DM+组发生不良反应率更髙, 两组间差异有统计学意义( P=0.029)。DM+组3个月痰菌阴转率80.0%(32/40), DM–组阴转率85.6%(149/174), 两组间差异无统计学意义( P>0.465)。 结论 DM+患者以中老年男性为主, 体质量指数(body mass index, BMI)相对较大, 要根据患者体重给与足量结核药以避免出现血 药浓度降低引起治疗效果不佳。DM+患者更容易出现影像学肺部空洞, 肺外结核病增多情况, 在临床上要警惕随时出 现大咯血可能, 注意周身多器官结核的排査。