scholarly journals One Step Forward: Successful End-of-Treatment Outcomes of Patients With Drug-Resistant Tuberculosis Who Received Concomitant Bedaquiline and Delamanid in Mumbai, India

2020 ◽  
Author(s):  
Mrinalini Das ◽  
Alpa Dalal ◽  
Chinmay Laxmeshwar ◽  
Shilpa Ravi ◽  
Fatima Mamnoon ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Scale Up ◽  
New Drugs ◽  
Drug Resistant ◽  
Serious Adverse Events ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
End Of Treatment ◽  
Conversion Rates ◽  
Culture Conversion

Abstract Background The Médecins Sans Frontières Clinic in Mumbai, India, has been providing concomitant bedaquiline (BDQ) and delamanid (DLM) in treatment regimen for patients with drug-resistant tuberculosis (DR-TB) and limited therapeutic options, referred from other healthcare institutions, since 2016. The study documents the end-of-treatment outcomes, culture-conversion rates, and serious adverse events (SAEs) during treatment. Methods This was a retrospective cohort study based on routinely collected program data. In clinic, treatment regimens are designed based on culture drug sensitivity test patterns and previous drug exposures, and are provided for 20–22 months. BDQ and DLM are extended beyond 24 weeks as off-label use. Patients who initiated DR-TB treatment including BDQ and DLM (concomitantly for at least 4 weeks) during February 2016–February 2018 were included. Results Of the 70 patients included, the median age was 25 (interquartile range [IQR], 22–32) years and 56% were females. All except 1 were fluoroquinolone resistant. The median duration of exposure to BDQ and DLM was 77 (IQR, 43–96) weeks. Thirty-nine episodes of SAEs were reported among 30 (43%) patients, including 5 instances of QTc prolongation, assessed as possibly related to BDQ and/or DLM. The majority (69%) had culture conversion before 24 weeks of treatment. In 61 (87%), use of BDQ and DLM was extended beyond 24 weeks. Successful end-of-treatment outcomes were reported in 49 (70%) patients. Conclusions The successful treatment outcomes of this cohort show that regimens including concomitant BDQ and DLM for longer than 24 weeks are effective and can be safely administered on an ambulatory basis. National TB programs globally should scale up access to life-saving DR-TB regimens with new drugs.

scholarly journals Strengthened capacity of India´s bedaquiline Conditional Access Programme for introducing new drugs and regimens

2020 ◽  
Vol 24 (10) ◽  
pp. 1067-1072
Author(s):  
K. S. Sachdeva ◽  
N. Arora ◽  
R. Solanki ◽  
R. Singla ◽  
R. Sarin ◽  
...  
Keyword(s):  
Scale Up ◽  
New Drugs ◽  
Serious Adverse Events ◽  
Conditional Access ◽  
Conversion Rates ◽  
Drug Safety Monitoring ◽  
Access Programme ◽  
Pre Treatment ◽  
Culture Conversion

BACKGROUND: Addressing TB in India is critical to meeting global targets. With the scale-up of diagnostic networks and the availability of new TB drugs, India had the opportunity to improve the detection and treatment outcomes in drug-resistant TB (DR-TB).OBJECTIVE: To document how the introduction of new drugs and regimens is helping India improve the care of DR-TB patients.DESIGN: In 2016, India´s National TB Programme (NTP) introduced bedaquiline (BDQ) under a Conditional Access Programme (BDQ-CAP) at six sites after providing extensive training and strengthening laboratory testing, pre-treatment evaluation, active drug safety monitoring and management (aDSM) and follow-up systems.RESULTS: An interim analysis reflected earlier and better culture conversion rates: 83% of the 620 patients converted within a median time of 60 days. However, 248 serious adverse events were reported, including 73 deaths (12%) and 100 cardiotoxicity events (16.3%). Encouraged by the evidence of safety and efficacy of BDQ, the NTP took steps to systematically expand its access to cover the entire population by 2018.CONCLUSION: The cautious yet focused approach used to introduce BDQ under BDQ-CAP paved the way for the rapid introduction of delamanid, as well as the shorter treatment regimen and the all-oral regimen for DR-TB.

scholarly journals Treatment outcomes in patients with drug-resistant TB-HIV co-infection treated with bedaquiline and linezolid

2020 ◽  
Vol 24 (10) ◽  
pp. 1024-1031
Author(s):  
N. Padayatchi ◽  
N. Bionghi ◽  
F. Osman ◽  
N. Naidu ◽  
N. Ndjeka ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Drug Resistant ◽  
Hiv Patients ◽  
Loss To Follow Up ◽  
Resistant Tuberculosis ◽  
End Of Treatment ◽  
Kwazulu Natal ◽  
Historic Control ◽  
Culture Conversion

BACKGROUND: Bedaquiline (BDQ) has not been extensively studied among patients co-infected with HIV drug-resistant tuberculosis (DR-TB). We compared treatment outcomes in DR-TB patients treated with BDQ- and linezolid (LZD) containing regimens to historic controls treated with second-line injectable-containing regimens.METHODS: Retrospective cohort study of consecutive DR-TB patients initiated on BDQ- and LZD-containing regimens at a TB referral hospital in KwaZulu-Natal, South Africa. Participants were prospectively followed through 24 months for treatment outcome and adverse events. Outcomes were compared to a historic control cohort of DR-TB HIV patients enrolled at the same facility prior to BDQ introduction.RESULTS: Adult DR-TB patients initiating BDQ between January 2014 and November 2015 were enrolled (n = 151). The majority of patients were female (52%), HIV co-infected (77%) and on antiretroviral therapy (100%). End of treatment outcomes included cure (63%), TB culture conversion (83%), completion (0.7%), loss to follow-up (15%), treatment failure (5%), and death (17%). Compared to historic controls (n = 105), patients treated with BDQ experienced significantly higher TB culture conversion and cure, with significantly lower mortality. Adverse effects were common (92%), and most frequently attributed to LZD (24.1%). QT segment prolongation was common but without clinical sequelae.CONCLUSION: Treatment with BDQ- and LZD-containing regimens was associated with improved treatment outcomes and survival in DR-TB HIV patients.

scholarly journals Effectiveness and safety of delamanid- or bedaquiline-containing regimens among children and adolescents with multidrug resistant or extensively drug resistant tuberculosis: A nationwide study from Belarus, 2015-19

2021 ◽  
Vol 91 (1) ◽  
Author(s):  
Varvara Solodovnikova ◽  
Ajay M.V. Kumar ◽  
Hennadz Hurevich ◽  
Yuliia Sereda ◽  
Vera Auchynka ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Multidrug Resistant ◽  
Post Treatment ◽  
New Drugs ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Culture Conversion

There is limited evidence describing the safety and effectiveness of bedaquiline and delamanid containing regimens in children and adolescents with Multidrug-Resistant Tuberculosis (MDR-TB) and Extensively Drug-Resistant Tuberculosis (XDR-TB) globally. In this nationwide descriptive cohort study from Belarus, we examined adverse drug events, time to culture conversion, treatment outcomes including post-treatment recurrence among children and adolescents (<18 years of age) treated with bedaquiline and/or delamanid containing regimens from 2015 to 2019. Of the 40 participants included (55% females; age range 10-17 years), 20 (50%) had XDR-TB and 15 (38%) had resistance to either fluoroquinolone or second-line injectable. Half of the patients received delamanid and another half received bedaquiline with one patient receiving both drugs. AEs were reported in all the patients. A total of 224 AEs were reported, most of which (76%) were mild in nature. Only 10 (5%) AEs were graded severe and one AE was graded life-threatening. A total of 7 AEs (3%) were classified as ‘serious’ and only one patient required permanent discontinuation of the suspected drug (linezolid). Most of the AEs (94%) were resolved before the end of treatment. All patients culture-positive at baseline (n=34) became culture-negative within three months of treatment. Median time to culture conversion was 1.1 months (interquartile range: 0.9-1.6). Two patients were still receiving treatment at the time of analysis. The remaining 38 patients successfully completed treatment. Among those eligible and assessed at 6 (n=32) and 12 months (n=27) post-treatment, no recurrences were detected. In conclusion, treatment of children and adolescents with MDR-TB and XDR-TB using bedaquiline and/or delamanid containing regimens was effective and had favourable safety profile. Achieving such excellent outcomes under programmatic settings is encouraging for other national tuberculosis programmes, which are in the process of introducing or scaling-up the use of these new drugs in their countries.

scholarly journals 1884. Clinical Outcomes Among Patients with Drug-Resistant Tuberculosis Receiving Bedaquiline or Delamanid Containing Regimens

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S52-S52
Author(s):  
Russell R Kempker ◽  
Lali Mikiashvili ◽  
Yuan Zhao ◽  
David Benkeser ◽  
Ketino Barbakadze ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Clinical Outcomes ◽  
Treatment Options ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Acquired Drug Resistance ◽  
Treatment Regimens ◽  
Resistant Tuberculosis ◽  
Conversion Rates ◽  
Culture Conversion

Abstract Background Bedaquiline and delamanid are new and much-needed treatment options for drug-resistant tuberculosis (TB); however, there are limited data guiding their use and no direct comparison of the two drugs. We thus sought to compare the clinical outcomes of patients with drug-resistant tuberculosis receiving either a bedaquiline- or delamanid-based treatment regimen. Methods This is a prospective observational study among patients with drug-resistant pulmonary TB in the country of Georgia from 2015 to 2017. Patients receiving bedaquiline or delamanid were eligible to be enrolled. Monthly sputum cultures and MIC testing on Mycobacterium tuberculosis isolates were performed. Clinical outcomes included time to culture conversion, rate of acquired drug resistance and treatment outcomes. Results Among 156 patients with MDR-TB who were approached, 100 were enrolled, and 95 were receiving a bedaquiline (n = 64) or delamanid (n = 31) based regimen and included in the study. Patients receiving bedaquiline or delamanid were similar with regards to age, BMI, substance use, comorbidities, rate of cavitary disease, and extensively drug-resistant (XDR) TB. Rates of additional Class A drug use including linezolid (78 vs. 81%) and a fluoroquinolone (39 vs. 36%) were similar and the mean effective drugs received per group was 4 (IQR 3–4, P = 0.33). Median drug duration was 171 days for bedaquiline and 182 days for delamanid; no patient discontinued due to QTC prolongation. Adjusted cumulative culture conversion rates at 60 days (64% vs. 48%, P = 0.14) and 180 days (95% vs. 77%, P = 0.02) were higher in patients receiving bedaquiline compared with delamanid (see figure). Rates of acquired drug resistance were higher in patients receiving delamanid compared with bedaquiline (35 vs. 12%, P < 0.01). Lastly, patients receiving a bedaquiline-based regimen had higher rates of favorable outcomes as compared with patients receiving delamanid (94% vs. 67%, P < 0.01). Conclusion Patients receiving bedaquiline- and delamanid-based treatment regimens for drug-resistant TB had similar characteristics and those receiving bedaquiline had better clinical outcomes. Our results provide an important first comparison of bedaquiline vs. delamanid containing regimens. Disclosures All Authors: No reported Disclosures.

scholarly journals Treatment outcomes of children and adolescents receiving drug-resistant TB treatment in a routine TB programme, Mumbai, India

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246639
Author(s):  
Shubhangi Dhakulkar ◽  
Mrinalini Das ◽  
Narendra Sutar ◽  
Vikas Oswal ◽  
Daksha Shah ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Children And Adolescents ◽  
Treatment Outcomes ◽  
Successful Treatment ◽  
Drug Resistant ◽  
Tb Treatment ◽  
Unsuccessful Treatment ◽  
End Of Treatment ◽  
Conversion Rates ◽  
Culture Conversion

Background Childhood and adolescent drug-resistant TB (DR-TB) is one of the neglected infectious diseases. Limited evidence exists around programmatic outcomes of children and adolescents receiving DR-TB treatment. The study aimed to determine the final treatment outcomes, culture conversion rates and factors associated with unsuccessful treatment outcome in children and adolescents with DR-TB. Methods This is a descriptive study including children (0–9 years) and adolescents (10–19 years) with DR-TB were who were initiated on ambulatory based treatment between January 2017-June 2018 in Shatabdi hospital, Mumbai, India where National TB elimination programme(NTEP) Mumbai collaborates with chest physicians and Médecins Sans Frontières(MSF) in providing comprehensive care to DR-TB patients. The patients with available end-of-treatment outcomes were included. The data was censored on February 2020. Result A total of 268 patients were included; 16 (6%) of them were children (0–9 years). The median(min-max) age was 17(4–19) years and 192 (72%) were females. Majority (199, 74%) had pulmonary TB. Most (58%) had MDR-TB while 42% had fluoroquinolone-resistant TB. The median(IQR) duration of treatment (n = 239) was 24(10–25) months. Median(IQR) time for culture-conversion (n = 128) was 3(3–4) months. Of 268 patients, 166(62%) had successful end-of-treatment outcomes (cured-112; completed treatment-54). Children below 10 years had higher proportion of successful treatment outcomes (94% versus 60%) compared to adolescents. Patients with undernutrition [adjusted odds-ratio, aOR (95% Confidence Interval, 95%CI): 2.5 (1.3–4.8) or those with XDR-TB [aOR (95% CI): 4.3 (1.3–13.8)] had higher likelihood of having unsuccessful DR-TB treatment outcome. Conclusion High proportion of successful treatment outcome was reported, better than global reports. Further, the nutritional support and routine treatment follow up should be strengthened. All oral short and long regimens including systematic use of new TB drugs (Bedaquiline and Delamanid) should be rapidly scaled up in routine TB programme, especially for the paediatric and adolescent population.

scholarly journals Drug-Resistant Tuberculosis: Correlation between Positivity of Acid-Fast Bacilli Sputum and Time to Conversion on Patients with Short-Term Treatment Regimen

2020 ◽  
Vol 14 (4) ◽  
pp. 2443-2451
Author(s):  
Tutik Kusmiati ◽  
Anita Nur Charisma ◽  
Nur Prasetyo Nugroho ◽  
Soedarsono
Keyword(s):  
Treatment Outcomes ◽  
Term Treatment ◽  
Drug Resistant ◽  
Short Term ◽  
Short Term Treatment ◽  
Drug Resistant Tuberculosis ◽  
Acid Fast Bacilli ◽  
Resistant Tuberculosis ◽  
Sputum Conversion ◽  
Culture Conversion

Drug-resistant tuberculosis (DR-TB) is a worldwide global burden and related to poor treatment outcomes. Monitoring the progress of DR-TB treatment can be carried out microscopic with Acid-Fast Bacilli (AFB) sputum smear and assessed from the beginning or the first time the patient is diagnosed and monthly to determine the sequential conversion of AFB baseline to the next month twice until it becomes negative. The prolonged conversion has been associated with infectiousness and treatment outcomes. This study was aimed to determine the correlation between positivity of AFB sputum and time to conversion in DR-TB patients with short-term treatment (STR) regimen. An analytic retrospective at hospital collected from medical records of DR-TB patients, from September 2017 to July 2018. Spearman technique was used to analyze the data with p < 0.05. From the total of 151 DR-TB patients on STR regimen, 51 patients were enrolled consisting of 30 (58.8%) males and 21 (41.2%) females with ages average were 51 ± 12.9 years old. Overall, 39 (76.5%) patients had time of AFB conversion in the first month, 9 (17.6%) patients in the second months, 2 (3.9%) patients in the third months, and 1 (2%) patient in the fourth months. Among those patients, 26 (51%) patients had completed the treatment outcomes, 22 (43.1%) were loss to follow-up, 1 (2%) patient had the treatment failure, and 2 (3.9%) were died. There was no significant correlation between AFB sputum baseline (Scanty, 1+, 2+, 3+) with the time to sputum conversion (p > 0.05). AFB sputum have significant correlation with time of culture conversion (p < 0.05), and treatment compliance was not associated with time of AFB sputum conversion (p > 0.05). There was no significant relation between positivity of AFB baseline and time to sputum conversion in DR-TB patients on short-term treatment (STR) regimen. AFB sputum have significant correlation with time of culture conversion in DR-TB patients on short-term treatment (STR) regimen.

scholarly journals Spatial clustering of drug-resistant tuberculosis in Hunan province, China: an ecological study

BMJ Open ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. e043685
Author(s):  
Kefyalew Addis Alene ◽  
Zuhui Xu ◽  
Liqiong Bai ◽  
Hengzhong Yi ◽  
Yunhong Tan ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Cumulative Incidence ◽  
Ecological Study ◽  
Spatial Clustering ◽  
Hunan Province ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
The North ◽  
Resistant Tuberculosis ◽  
Over Time

ObjectiveThis study aimed to investigate the spatial distribution of drug-resistant tuberculosis (DR-TB) in Hunan province, China.MethodsAn ecological study was conducted using DR-TB data collected from the Tuberculosis Control Institute of Hunan Province between 2012 and 2018. Spatial clustering of DR-TB was explored using the Getis-Ord statistic. A Poisson regression model was fitted with a conditional autoregressive prior structure, and with posterior parameters estimated using a Bayesian Markov chain Monte Carlo simulation, to quantify associations with possible risk factors and identify clusters of high DR-TB risk.ResultsA total of 2649 DR-TB patients were reported to Hunan TB Control Institute between 2012 and 2018. The majority of the patients were male (74.8%, n=1983) and had a history of TB treatment (88.53%, n=2345). The proportion of extensively DR-TB among all DR-TB was 3.3% (95% CI 2.7% to 4.1%), which increased from 2.8% in 2012 to 4.4% in 2018. Of 1287 DR-TB patients with registered treatment outcomes, 434 (33.8%) were cured, 198 (15.3%) completed treatment, 92 (7.1%) died, 108 (8.3%) had treatment failure and 455 (35.3%) were lost to follow-up. Half (50.9%, n=655) had poor treatment outcomes. The annual cumulative incidence rate of notified DR-TB increased over time from 0.25 per 100 000 people in 2012 to 0.83 per 100 000 people in 2018. Substantial spatial heterogeneity was observed, and hotspots were detected in counties located in the North and East parts of Hunan province. The cumulative incidence of notified DR-TB was significantly associated with urban communities.ConclusionThe annual incidence of notified DR-TB increased over time in Hunan province. Spatial clustering of DR-TB was detected and significantly associated with urbanisation. This finding suggests that targeting interventions to the highest risk areas and population groups would be effective in reducing the burden and ongoing transmission of DR-TB.

scholarly journals Trends, Characteristics and Treatment Outcomes of Patients with Drug-Resistant Tuberculosis in Uzbekistan: 2013–2018

2021 ◽  
Vol 18 (9) ◽  
pp. 4663
Author(s):  
Khasan Safaev ◽  
Nargiza Parpieva ◽  
Irina Liverko ◽  
Sharofiddin Yuldashev ◽  
Kostyantyn Dumchev ◽  
...  
Keyword(s):  
Risk Factors ◽  
Treatment Outcomes ◽  
Treatment Success ◽  
National Level ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Loss To Follow Up ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Uzbekistan has a high burden of drug-resistant tuberculosis (TB). Although conventional treatment for multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) has been available since 2013, there has been no systematic documentation about its use and effectiveness. We therefore documented at national level the trends, characteristics, and outcomes of patients with drug-resistant TB enrolled for treatment from 2013–2018 and assessed risk factors for unfavorable treatment outcomes (death, failure, loss to follow-up, treatment continuation, change to XDR-TB regimen) in patients treated in Tashkent city from 2016–2017. This was a cohort study using secondary aggregate and individual patient data. Between 2013 and 2018, MDR-TB numbers were stable between 2347 and 2653 per annum, while XDR-TB numbers increased from 33 to 433 per annum. At national level, treatment success (cured and treatment completed) for MDR-TB decreased annually from 63% to 57%, while treatment success for XDR-TB increased annually from 24% to 57%. On multivariable analysis, risk factors for unfavorable outcomes, death, and loss to follow-up in drug-resistant TB patients treated in Tashkent city included XDR-TB, male sex, increasing age, previous TB treatment, alcohol abuse, and associated comorbidities (cardiovascular and liver disease, diabetes, and HIV/AIDS). Reasons for these findings and programmatic implications are discussed.

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