MDR-TB Treatment Research Articles

Design, Synthesis, Pharmacological Evaluation, In silico Modeling, Prediction of Toxicity and Metabolism Studies of Novel 1-(substituted)-2-methyl- 3-(4-oxo-2-phenyl quinazolin-3(4H)-yl)isothioureas.

Although exhaustive efforts to prevent and treat tuberculosis (TB) have been made, the problem still continues due to multi-drug-resistant (MDR) and extensively drugresistant TB (XDR-TB). It clearly highlights the urgent need to develop novel "druggable" molecules for the co-infection treatment and strains of MDR-TB and XDR-TB. In this approach, a hybrid molecule was created by merging two or more pharmacophores. The active site of targets may be addressed by each of the pharmacophores and proffers the opportunity for selectivity. In addition, it also reduces undesirable side effects and drug-resistance. In this study, a novel quinazolinone analog was designed and synthesized by substituting thiourea nucleus and phenyl ring at N-3 and C-2 position of quinazoline ring, respectively. All title compounds were tested for antitubercular activity by in vitro M. tuberculosis and anti-human immunodeficiency virus (HIV) activity by MT-4 cell assay method. The agar dilution method was used to test the antibacterial potency of entire prepared derivatives against various strains of grampositive and gram-negative microorganisms. The title compounds, 1-(substituted)-2-methyl-3-(4-oxo-2-phenyl quinazolin-3(4H)-yl) isothioureas (QTS1 - QTS15) were synthesized by the reaction between key intermediate 3-amino- 2-phenylquinazolin-4(3H)-one with various alkyl/aryl isothiocyanates followed by methylation with dimethyl sulphate. Among the series, compound 1-(3-chlorophenyl)-2-methyl-3-(4-oxo-2-phenyl quinazolin- 3(4H)-yl) isothioureas (QTS14) showed the highest potency against B. subtilis, K. pneumonia and S. aureus at 1.6 μg/mL. The compound QTS14 exhibited the most potent antitubercular activity at the MIC of 0.78 μg/mL and anti-HIV activity at 0.97 μg/mL against HIV1 and HIV2. The results obtained from this study confirm that the synthesized and biologically evaluated quinazolines showed promising antimicrobial, antitubercular and anti-HIV activities. The new scaffolds proffer a plausible lead for further development and optimization of novel antitubercular and anti-HIV drugs.

Cost-effectiveness of treating multidrug-resistant tuberculosis in treatment initiative centers and treatment follow-up centers in Ethiopia.

BackgroundIn Ethiopia, MDR-TB has become a significant public health threat; therefore, the Ministry of Health introduced two treatment approaches for MDR-TB cases: treatment initiative center (TIC) and treatment follow-up center (TFC). TIC is where patients usually are diagnosed and start the treatment. At TFC, we follow MDR-TB patients until they completed the treatment. However, there is no evidence about the cost-effectiveness of the approaches. Therefore, this study aimed to analyze the cost-effectiveness of MDR-TB treatment in TIC and TFC.MethodsIn this study, we employed a full economic evaluation from a providers' perspective. We followed a hypothetical cohort of individuals from the age of 15 for a lifetime using a Markov model with five mutually exclusive health states. We used both primary and secondary data sources for the study. Ingredient-based costing approach was used. The costs include healthcare provider costs (recurrent and capital cost) and patient-side costs (direct and indirect). We use a human capital approach to estimate the indirect cost. The cost estimates were reported in the 2017 United States Dollar (US$), and effectiveness was measured using disability-adjusted life-years (DALYs) averted. Both costs and health benefits were discounted using a 3% discount rate. Both average and incremental cost-effectiveness ratios (ICER) were reported calculated. One-way and probabilistic sensitivity analyses were reported to determine the robustness of the estimates.ResultsThe cost per HIV negative patient successfully treated for MDR-TB was $8,416 at TIC and $6,657 at TFC. The average cost-effectiveness ratio per DALY averted at TFC was $671 and $1,417 per DALY averted at TIC. The incremental cost-effectiveness ratio (ICER) of MDR-TB treatment at TIC was $1,641 per DALYs averted.ConclusionThis study indicates that the treatment of MDR-TB at both TIC and TFC are cost-effective interventions compared with the willingness to pay threshold of three-times the GDP per capita in Ethiopia.

Liaison of Sugar Control With Time to Sputum Culture Conversion in Multi-Drug Resistant Tuberculosis.

BackgroundMany elements have been studied repeatedly that influence time to sputum culture conversion in multi-drug resistant tuberculosis (MDR-TB). Deranged sugars not only hamper one’s infection contesting ability but also increase the chances of drug resistance. Our aim was to establish whether or not glycemic control alters MDR-TB treatment outcome.MethodsA prospective cohort study was conducted at the TB Clinic of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Newly diagnosed MDR-TB cases were started on WHO-recommended treatment regime. HbA1c (hemoglobin A1c or glycated hemoglobin) was tested at the start of treatment irrespective of the previous diabetic status. Sputum samples, 30 days apart, were taken during the initial phase of the MDR TB treatment until two consecutive samples showed conversion. Pearson's correlation coefficient was calculated to see the link between time to sputum culture conversion and HbA1c.ResultsAmong 47 patients, 19 (40.4%) new cases, whereas 28 (59.8%) were previously treated for drug-sensitive TB. Our 39 patients converted during six months, of which 18 (46%) converted in one month, 14 (35.9%) in two months, 6 (15.4%) in three months, and only 1 in five months. Mean time to sputum culture conversion was 1.77 ± 0.9 months. There was a slightly negative correlation between HbA1c and sputum culture conversion time (r = -0.075, p = 0.649).ConclusionsSugar control does not affect sputum culture conversion in MDR-TB when an optimal treatment regime is applied.

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

BackgroundThe 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). Objectiveto 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. MethodsWe recruited a total of 168 patients with MDR-TB and DS-TB each, in Delhi. Data were analyzed using IBM SPSS Version 25. ResultsThe 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). ConclusionsDespite 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.

Treatment outcome of multi-drug resistant tuberculosis patients on second line anti-tuberculosis dugs at tertiary care hospital at Himachal Pradesh, India

Background: MDR-TB treatment defaulter are potentially harmful to community as these can relapse and spread infection, developed resistance to second line anti tubercular drugs and may result in to extensive drug resistant tuberculosis (XDR-TB) and major challenges for successful outcome. Objective was to study treatment outcome of multi-drug resistant tuberculosis patients on second line anti-tuberculosis drugs at tertiary care hospital at Himachal Pradesh.Methods: It was prospective observational study carried out after approval from institutional ethics committee. A total 104 MDR/RR-TB case enrolled for study from November 2012 to October 2013. Data were collected in predesigned proforma and entered in to Microsoft excel worksheet 2007 and analyzed with the help of SPSS software version 17. Chi-square test was applied to find out the association between independent variable and outcome of MDR-TB and p&lt;0.05 was considered statistically significant.Results: Among all 104 patients initiated on treatment 73.07% patients were alive, completed intensive phase and switch to continuation phase of treatment, 14.42% patients were died, 5.76% defaulted, 0.96% patient was transferred out and 5.76% patients were turned out XDR-TB and switched to regimen of XDR-TB treatment.Conclusions: Treatment and control of MDR-TB require sound infrastructure and well equipped laboratory facilities to provide quality and prompt diagnosis. Lack of knowledge, awareness, long duration of treatment and defaulters are major challenges for successful outcome.

Clinical features associated with linezolid resistance among multidrug resistant tuberculosis patients at a tertiary care hospital in Mumbai, India

BackgroundMultidrug-resistant tuberculosis (MDR-TB) is an increasing problem worldwide, and 24% occurs in India. Linezolid is associated with improved MDR-TB treatment outcomes but causes significant side-effects and drug susceptibility testing (DST) is rarely available. This study assessed whether clinical factors could predict linezolid resistance. MethodsAn observational cohort of adults and adolescents with MDR-TB at a tertiary care hospital in Mumbai, India was analyzed for clinical, laboratory, and radiographic findings associated with linezolid resistance. ResultsIn total, 343 MDR-TB patients had linezolid DST performed, and 23 (6.7%) had linezolid-resistant MDR-TB. Univariable analysis associated linezolid resistance with underweight (odds ratio (OR)–1.07, 95% confidence interval (CI):1.01–1.12); number of previous providers (OR:1.03, 95% CI:1.00–1.05); previous treatment with linezolid (OR:1.12, 95% CI:1.06–1.05), bedaquiline (OR:1.55, 95% CI:1.22–1.98), or clofazimine (OR:1.08 95% CI:1.03–1.16); cavitary disease (OR:1.10, 95% CI:1.04–1.16) and percent lung involvement (OR:1.02, 95% CI:1.01–1.03) on radiograph. DST associated linezolid resistance with resistance to fluoroquinolones (OR:1.08, 95% CI:1.01–1.14), injectables (OR:1.09, 95% CI:1.03–1.15), ethionamide (OR:1.09, 95% CI:1.03–1.15), and PAS (OR:1.13, 95% CI:1.06–1.21). In multivariate analysis, only prior linezolid and percent lung involvement were associated with linezolid resistance. ConclusionTo maximize treatment benefits while minimizing toxicity, DST remains an important tool to identify linezolid resistance.

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.

The Influence of Distance from Health Facility, Family Number at Home and TB History in Starting Treatment of MDR-TB in Medan

The national TB Program according to the long-term plan is to prevent and control of drug resistance through Management Program of MDR-TB. The objective of the program are reducing morbidity, mortality and transmission of MDR-TB. Medan is an area with the highest case of MDR-TB in Sumatera Utara Province. Until November 2018 MDR-TB case has been confirmed in the city of Medan as many as 324, which has not started the treatment are 61 patients (19%). This research using case-control design and population is all people with MDR-TB in Medan city that recorded in E-TB Manager data. Sample case is the confirmed MDR-TB person who has not started the treatment as many as 13 people while the control is a confirmed person MDR-TB and willing to start the treatment as many as 31 people. The data is collected through interview using questionnaires and has received approval from the Ethics committee of the Faculty of Nursing University of Sumatera Utara. The data analysis is conducted with the chi-square test and the OR calculation to assess which variables affect the action of beginning MDR-TB treatment. Results showed that there was no influence of the distance of health facilities (p = 0.188) and family number at home (p = 0.507) with the status of starting treatment MDR-TB. There was influence of historical of TB with the status of starting treatment respondent MDR-TB (p = 0.021)

Changes in treatment for multidrug-resistant tuberculosis according to national income.

The aim of this study was to analyse temporal changes in treatments for and outcomes of multidrug-resistant (MDR)/rifampin-resistant (RR)-tuberculosis (TB) in the context of national economic status.We analysed data collected by the Collaborative Group for the Meta-Analysis of Individual Patient Data in MDR-TB Treatment on MDR/RR-TB patients from 37 countries. The data were stratified by three national income levels (low-/lower-middle, upper-middle and high) and grouped by time of treatment initiation (2001-2003, 2004-2006, 2007-2009, 2010-2012 and 2013-2015). Temporal trends over the study period were analysed. The probability of treatment success in different income groups over time was calculated using generalised linear mixed models with random effects.In total, 9036 patients were included in the analysis. Over the study period, use of group A drugs (levofloxacin/moxifloxacin, bedaquiline and linezolid) recommended by the World Health Organization increased and treatment outcomes improved in all income groups. Between 2001-2003 and 2013-2015, treatment success rates increased from 60% to 78% in low-/lower-middle-income countries, from 40% to 67% in upper-middle-income countries, and from 73% to 81% in high-income countries. In earlier years, the probability of treatment success in upper-middle-income countries was lower than that in low-/lower-middle-income countries, but no difference was observed after 2010. However, high-income countries had persistently higher probability of treatment success compared to upper-middle income countries.Improved treatment outcomes and greater uptake of group A drugs were observed over time for patients with MDR/RR-TB at all income levels. However, treatment outcomes are still unsatisfactory, especially in upper-middle-income countries.

Rising challenge of multidrug-resistant tuberculosis in China: a predictive study using Markov modeling

BackgroundMultidrug-resistant tuberculosis (MDR-TB) is on the rise in China. This study used a dynamic Markov model to predict the longitudinal trends of MDR-TB in China by 2050 and to assess the effects of alternative control measures.MethodsEight states of tuberculosis transmission were set up in the Markov model using a hypothetical cohort of 100 000 people. The prevalence of MDR-TB and bacteriologically confirmed drug-susceptible tuberculosis (DS-TB+) were simulated and MDR-TB was stratified into whether the disease was treated with the recommended regimen or not.ResultsWithout any intervention changes to current conditions, the prevalence of DS-TB+ was projected to decline 67.7% by 2050, decreasing to 20 per 100 000 people, whereas that of MDR-TB was expected to triple to 58/100 000. Furthermore, 86.2% of the MDR-TB cases would be left untreated by the year of 2050. In the case where MDR-TB detection rate reaches 50% or 70% at 5% per year, the decline in prevalence of MDR-TB would be 25.9 and 36.2% respectively. In the case where treatment coverage was improved to 70% or 100% at 5% per year, MDR-TB prevalence in 2050 would decrease by 13.8 and 24.1%, respectively. If both detection rate and treatment coverage reach 70%, the prevalence of MDR-TB by 2050 would be reduced to 28/100 000 by a 51.7% reduction.ConclusionsMDR-TB, especially untreated MDR-TB, would rise rapidly under China’s current MDR-TB control strategies. Interventions designed to promote effective detection and treatment of MDR-TB are imperative in the fights against MDR-TB epidemics.

Adherence to the MDR-TB intensive phase treatment protocol amongst individuals followed up at central and peripheral health care facilities in Uganda - a descriptive study.

Following initiation of MDR-TB treatment, patients have a choice to receive follow up DOT supervision at either the central initiating facility or at a peripheral facility. We describe the adherence patterns of MDR-TB patients undergoing DOT supervision at the two health facility categories during intensive phase of treatment. We used a retrospective cohort of patients initiated on MDR TB treatment at Mulago National Referral Hospital between 2014 and 2016. We extracted data from the National Tuberculosis and Leprosy Program records and analysed these using STATA V14. Majority (84.01%) of the patients received their DOT supervision from the peripheral facilities. Males made up 62.1% of patients, and 91.2% had had their household contacts screened for MDR-TB. 26.5% of the patients on peripheral DOT supervision had good adherence to treatment protocol compared to 0% among patients on central initiating health facility DOT supervision. Among the patients with good adherence, 24.1% had contacts screened for MDR-TB as compared to 3.6% with poor adherence. More patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settingsMore patients preferred MDR-TB DOT supervision at peripheral facilities, which had better adherence to the treatment protocol compared to the central initiating facility. Younger people and those with household contacts screened had better adherence to the treatment protocol, highlighting areas for targeted interventional programs for MDR-TB in resource limited settings.

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 the diagnostic rate was high in public HCF. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

Obstructive lung disease and quality of life after cure of multi-drug-resistant tuberculosis in Uganda: a cross-sectional study

BackgroundPulmonary multi-drug-resistant tuberculosis (MDR TB) alters lung architecture and involves lengthy treatment duration, high pill burden, drug adverse effects, travel restrictions, and stigma. Literature about pulmonary function and health-related quality of life (QoL) of patients treated for MDR TB is limited. This study sought to determine the prevalence of chronic obstructive pulmonary disease (COPD) and QoL of patients who were treated for pulmonary MDR TB.MethodsParticipants who completed 18 months of pulmonary MDR TB treatment and considered cured were eligible to be evaluated in a cross-sectional study. We performed post-bronchodilator spirometry to measure forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). COPD was defined as FEV1/FVC < 0.7; health-related QoL was assessed using the Medical Outcomes Survey for HIV (MOS-HIV) and St. George’s Respiratory Questionnaire (SGRQ). Linear and logistic regression models were used to assess associations with COPD, health-related QoL, and other characteristics of the cohort.ResultsA total of 95 participants were enrolled. Median age of the cohort was 39 years (interquartile range (IQR), 29–45), and 55 (58%) were HIV-positive. COPD prevalence was 23% (22/95). Median SGRQ score was normal at 7.8 (IQR, 3.1–14.8). Median mental and physical health summary scores were significantly impaired, at 58.6 (IQR, 52.0–61.5) and 52.9 (IQR, 47.8–57.9), respectively, on a scale of 0 to 100 where 100 represents excellent physical or mental health. In this sample, 19% (18/95) of participants were in the lowest relative socioeconomic position (SEP) while 34% (32/95) were in the highest relative SEP. Belonging in the lowest SEP group was the strongest predictor of COPD.ConclusionIndividuals who have completed MDR TB treatment have a high prevalence of COPD and low mental and physical health summary scores. Our study highlights the need for pulmonary rehabilitation programs in patients with a low socioeconomic position (SEP) after MDR TB treatment.

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 the diagnostic yield was high in public HCF. The government should involve private HCFs to provide standard diagnostics and treatment to the patients seeking a private facility.

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.

Multidrug-resistant tuberculosis in the Kharkiv Region, Ukraine.

OBJECTIVE: To document the level of drug resistance in MDR-TB patients and to characterize management capacities for their medical care and MDR-TB treatment outcomes in the Kharkiv region of Ukraine. This area has one of the highest frequencies of MDR-TB worldwide.METHODS: A retrospective observational cohort study was performed on registry data from the regional anti-TB dispensary in Kharkiv. All microbiologically confirmed MDR-TB patients registered in 2014 were included. Diagnostic, treatment and post-treatment follow-up data were analysed.RESULTS: Of 169 patients with MDR-TB, 55.0% had pre-extensively drug-resistant (pre-XDR) or XDR resistant patterns. Rapid molecular diagnosis by GeneXpert and liquid M. tuberculosis cultures were only available for 66.9% and 56.8% of patients, respectively. Phenotypic drug-susceptibility testing (DST) for high priority TB drugs (bedaquiline, linezolid, clofazimine) were not available. DST for later generation fluroquinolones was available only in 53.2% of patients. 50.9% of patients had less than 4 drugs in the treatment regimen proven to be effective by DST. More than 23.1% of patients with MDR-TB failed their treatment and only 45.0% achieved a cure.CONCLUSION: The high prevalence of MDR-TB and poor MDR-TB treatment outcomes in the Kharkiv region, is associated with substantial shortages in rapid molecular and phenotypic DST, a lack of high priority MDR-TB drugs, poor treatment monitoring and follow-up capacities.

Improved treatment outcome of multidrug-resistant tuberculosis with the use of a rapid molecular test to detect drug resistance in China

ObjectivesNumerous studies investigate the advantages of rapid molecular drug susceptibility testing (DST) in comparison to phenotypic DST, but the clinical impact on treating multi/extensively drug resistant TB(M/XDR-TB) is less studied. Therefore, we examined how molecular DST testing may improve MDR-TB treatment management and outcome in Chinese settings. MethodsWe performed a comparative study of patient cohorts before and after the implementation of molecular DST diagnosis with Genotype MTBDRsl/MTBDRplus assay in two Chinese hospitals. We collected clinical information including time to sputum culture conversion and final treatment outcome. ResultsIn total, 242 MDR-TB patients were studied including 114 before (pre-implementation group) and 128 after the implementation (post-implementation group) of molecular DST. Time to MDR-TB diagnosis was significantly reduced for patients in the post-implementation group, as compared to the pre-implementation group (median,16 vs 62 days; P < 0.001). Patients with early available molecular DST results had a more rapid culture conversion (aHR1.94 95% CI: 1.37-2.73; median,12 vs 24 months, respectively; P < 0.001) and higher rate of treatment success (68% vs 47%, P < 0.01). ConclusionsThe use of molecular DST in routine care for MDR-TB diagnosis as compared to phenotypic DST was associated with a decreased time to culture conversion and improved treatment outcome, highlighting its important clinical value.

Managing multidrug-resistant tuberculosis in South Africa: a budget impact analysis.

SETTING: In South Africa prior to 2016, the standard treatment regimen for multidrug- and rifampicin-resistant tuberculosis (MDR/RR-TB) was 24 months long and required daily injectable aminoglycoside (IA) treatment during the first 6 months. Recent evidence supports the replacement of IA with well-tolerated oral bedaquiline (BDQ) and a shortened 9-12 month regimen.DESIGN: Using a Markov model, we analyzed the 5-year budgetary impact and cost per successful treatment outcome of four regimens: 1) IA long-course, 2) oral long-course, 3) IA short-course, and 4) oral short-course. We used the South African MDR/RR-TB case register (2013-2015) to assess treatment outcomes for the then-standard IA long-course. Data on the improvement in outcomes for BDQ-based regimens were based on the literature. Costs were estimated from the provider perspective using costs incurred to provide decentralized treatment for MDR-TB at a Johannesburg hospital.RESULTS: Based on our analysis, by 2023, the cost/successful outcome for the four regimens was respectively 1) US$7374, 2) US$7860, 3) US$5149, and 4) US$4922. The annual total cost of each regimen was US$37 million, US$43 million, US$26 million, and US$28 million.CONCLUSION: Despite the high cost of BDQ, a BDQ-based shortened regimen for the treatment of MDR/RR-TB will result in improved treatment outcomes and cost savings for South Africa.

Risk factors for poor treatment outcomes of 2266 multidrug-resistant tuberculosis cases in Ho Chi Minh City: a retrospective study

BackgroundMultidrug resistant tuberculosis (MDR-TB) remains a serious public health problem with poor treatment outcomes. Predictors of poor outcomes vary in different regions. Vietnam is among the top 30 high burden of MDR-TB countries. We describe demographic characteristics and identify risk factors for poor outcome among patients with MDR-TB in Ho Chi Minh City (HCMC), the most populous city in Vietnam.MethodsThis retrospective study included 2266 patients who initiated MDR-TB treatment between 2011 and 2015 in HCMC. Treatment outcomes were available for 2240 patients. Data was collected from standardized paper-based treatment cards and electronic records. A Kruskal Wallis test was used to assess changes in median age and body mass index (BMI) over time, and a Wilcoxon test was used to compare the median BMI of patients with and without diabetes mellitus. Chi squared test was used to compare categorical variables. Multivariate logistic regression with multiple imputation for missing data was used to identify risk factors for poor outcomes. Statistical analysis was performed using R program.ResultsAmong 2266 eligible cases, 60.2% had failed on a category I or II treatment regimen, 57.7% were underweight, 30.2% had diabetes mellitus and 9.6% were HIV positive. The notification rate increased 24.7% from 2011 to 2015. The treatment success rate was 73.3%. Risk factors for poor treatment outcome included HIV co-infection (adjusted odds ratio (aOR): 2.94), advanced age (aOR: 1.45 for every increase of 5 years for patients 60 years or older), having history of MDR-TB treatment (aOR: 5.53), sputum smear grade scanty or 1+ (aOR: 1.47), smear grade 2+ or 3+ (aOR: 2.06), low BMI (aOR: 0.83 for every increase of 1 kg/m2 of BMI for patients with BMI < 21).ConclusionThe number of patients diagnosed with MDR-TB in HCMC increased by almost a quarter between 2011 and 2015. Patients with HIV, high smear grade, malnutrition or a history of previous MDR-TB treatment are at greatest risk of poor treatment outcome.

The burden of pre-extensively and extensively drug-resistant tuberculosis among MDR-TB patients in the Amhara region, Ethiopia.

BackgroundThe emergence of pre-extensively and extensively drug-resistant tuberculosis (Pre-XDR/XDR-TB) is the major hurdle for TB prevention and care programs especially in developing countries like Ethiopia. The less emphasis on universal access to laboratory techniques for the rapid diagnosis of TB and drug susceptibility testing (DST) makes the management of MDR-TB a challenge. Early detection of second line anti-TB drugs resistance is essential to reduce transmission of Pre-XDR/XDR-TB strains and adjusting the treatment regimen in MDR-TB.ObjectiveTo determine the prevalence and resistance pattern of Pre-XDR- and XDR-TB among MDR-TB patients in the Amhara region, Ethiopia.MethodsA cross sectional study was carried out in nine MDR-TB treatment centers in the Amhara region. Sputum samples were collected from all pulmonary rifampicin resistant (RR) or MDR-TB patients prior to anti-TB treatment. Lӧwenstein-Jensen (LJ) culture, Ziehl Neelsen (ZN) smear, MTBDRplus and MTBDRsl assays were performed according to the standard procedures. Data were analyzed using SPSS 20 software. Chi-square and/or Fishers exact test was employed.ResultsOverall, 6.3% of MDR-TB isolates were resistant to at least one second line drugs. Pre-XDR-TB and XDR-TB isolates accounted 5.7% and 0.6% respectively. Moreover, 3.4% were resistant to FQs and 3.4% were resistant to second line injectable drugs. All isolates were susceptible for low level kanamycin. Almost all pre-XDR-TB strains (90%) were previously treated with anti-TB drugs. Drug resistant Mycobacterium tuberculosis isolates were disproportionately distributed in districts of the Amhara region and the majorities were concentrated in urban areas.ConclusionsThe high proportion of MDR-TB patients resistant to at least one second line drug is alarming. Strengthening the laboratory facilities to monitor pre-XDR and XDR-TB patients is crucial. The TB programs need to give emphasis on the effective and rational use of second line drugs for newly diagnosed MDR-TB patients to prevent the emergence of pre-XDR/XDR-TB strains.