scholarly journals Predicting the Outcomes of New Short-Course Regimens for Multi-Drug Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modelling

2018 ◽  
Author(s):  
Tan N Doan ◽  
Pengxing Cao ◽  
Theophilus I Emeto ◽  
James M McCaw ◽  
Emma S McBryde
Keyword(s):  
Treatment Duration ◽  
Treatment Success ◽  
Empirical Evaluation ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb

ABSTRACTShort-course regimens for multi-drug resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug, bedaquiline (BDQ), may have the potential to shorten MDR-TB treatment to less than six months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modelling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modelling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (four months) while still maintaining a very high treatment success rate (100% for daily BDQ for two weeks, or 95% for daily BDQ for one week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes then we anticipate clear cost-savings and a subsequent improvement in the efficiency of national TB programs.

scholarly journals Predicting the Outcomes of New Short-Course Regimens for Multidrug-Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modeling

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Tan N. Doan ◽  
Pengxing Cao ◽  
Theophilus I. Emeto ◽  
James M. McCaw ◽  
Emma S. McBryde
Keyword(s):  
Treatment Duration ◽  
Treatment Success ◽  
Empirical Evaluation ◽  
Multidrug Resistant ◽  
Pharmacodynamic Modeling ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb

ABSTRACT Short-course regimens for multidrug-resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug bedaquiline (BDQ) may have the potential to shorten MDR-TB treatment to less than 6 months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modeling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modeling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (4 months) while still maintaining a very high treatment success rate (100% for daily BDQ for 2 weeks, or 95% for daily BDQ for 1 week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes, then we anticipate clear cost savings and a subsequent improvement in the efficiency of national TB programs.

scholarly journals Prevalence and factors associated with non-adherence to multi-drug resistant tuberculosis (MDR-TB) treatment at Mulago National Referral Hospital, Kampala, Uganda

2021 ◽  
Vol 21 (1) ◽  
pp. 238-47
Author(s):  
Charles Batte ◽  
Martha S Namusobya ◽  
Racheal Kirabo ◽  
John Mukisa ◽  
Susan Adakun ◽  
...  
Keyword(s):  
Mulago Hospital ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Factors Associated ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
History Of ◽  
Previously Treated

Background: In Uganda, 12% of previously treated TB cases and 1.6% of new cases have MDR-TB and require specialized treatment and care. Adherence is crucial for improving MDR-TB treatment outcomes. There is paucity of information on the extent to which these patients adhere to treatment and what the drivers of non-adherence are. Methods: We conducted a cohort study using retrospectively collected routine program data for patients treated for MDR- TB between January 2012 – May 2016 at Mulago Hospital. We extracted anonymized data on non-adherence (missing 10% or more of DOT), socio-economic, demographic, and treatment characteristics of the patients. All participants were sen- sitive to MDR-TB drugs after second line Drug Susceptible Testing (DST) at entry into the study. Factors associated with non-adherence to MDR-TB treatment were determined using generalized linear models for the binomial family with log link and robust standard errors. We considered a p- value less than 0.05 as statistically significant. Results: The records of 227 MDR- TB patients met the inclusion criteria, 39.4% of whom were female, 32.6% aged be- tween 25 – 34 years, and 54.6% living with HIV/AIDS. About 11.9% of the patients were non-adherent. The main driver for non-adherence was history of previous DR-TB treatment; previously treated DR-TB patients were 3.46 (Adjusted prev- alence ratio: 3.46, 95 % CI: 1.68 - 7.14) times more likely to be non-adherent. Conclusion: One in 10 MDR-TB patients treated at Mulago hospital is non-adherent to treatment. History of previous DR- TB treatment was significantly associated with non-adherence in this study. MDR-TB program should strengthen adherence counselling, strengthen DST surveillance, and close monitoring for previously treated DR-TB patients. Keywords: Non-adherence; multi-drug resistant tuberculosis; treatment.

scholarly journals Adverse Drug Reactions in Patients put on Multi Drug Resistant Tuberculosis (MDR-TB) Treatment in Seven Districts of Central Gujarat

2015 ◽  
Vol 7 (4s) ◽  
pp. 425-431 ◽  
Author(s):  
Sangita Vashrambhai Patel ◽  
Nimavat Kapil Bhikhubhai ◽  
Alpesh Bhimabhai patel ◽  
Kalpita Samrat Shringarpure ◽  
Kedar Gautambhai Mehta ◽  
...  
Keyword(s):  
Adverse Drug Reactions ◽  
Drug Resistant ◽  
Drug Reactions ◽  
Drug Resistant Tuberculosis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb

scholarly journals Prevalence and risk factors of multi-drug resistant tuberculosis in Dalian, China

2017 ◽  
Vol 45 (6) ◽  
pp. 1779-1786 ◽  
Author(s):  
Xin-Tong Lv ◽  
Xi-Wei Lu ◽  
Xiao-Yan Shi ◽  
Ling Zhou
Keyword(s):  
Risk Factors ◽  
Population History ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Previously Treated Patients ◽  
Previously Treated

Objectives To investigate the prevalence and risk factors associated with multi-drug resistant tuberculosis (MDR–TB) in Dalian, China. Methods This was a retrospective review of data from patients attending a TB clinic in Dalian, China between 2012 and 2015. Demographic and drug susceptibility data were retrieved from TB treatment cards. Univariate logistic analysis was used to assess the association between risk factors and MDR–TB. Results Among the 3552 patients who were smear positive for Mycobacterium tuberculosis (MTB), 2918 (82.2%) had positive MTB cultures and 1106 (31.1%) had isolates that showed resistance to at least one drug. The overall prevalence of MDR–TB was 10.1% (359/3552; 131/2261 [5.8%] newly diagnosed and 228/1291 [17.7%] previously treated patients). Importantly, 75 extensively drug-resistant TB isolates were detected from 25 newly treated and 50 previously treated patients. In total, 215 (6.1%) patients were infected with a poly-resistant strain of MTB. Previously treated patients and older patients were more likely to develop MDR–TB. Conclusions The study showed a high prevalence of MDR–TB among the study population. History of previous TB treatment and older age were associated with MDR–TB.

scholarly journals S2 Multi-drug Resistant Tuberculosis (MDR-TB) treatment in the UK: a survey of injectable use and toxicity in practice

Thorax ◽  
2010 ◽  
Vol 65 (Suppl 4) ◽  
pp. A4-A5
Author(s):  
A. Sturdy ◽  
A. Goodman ◽  
R. J. Jose ◽  
A. Loyse ◽  
M. O'Donoghue ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Uk

scholarly journals Addressing the drug-resistant tuberculosis challenge through implementing a mixed model of care in Uganda

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0244451
Author(s):  
Samuel Kasozi ◽  
Nicholas Sebuliba Kirirabwa ◽  
Derrick Kimuli ◽  
Henry Luwaga ◽  
Enock Kizito ◽  
...  
Keyword(s):  
Mixed Model ◽  
Treatment Initiation ◽  
Treatment Success ◽  
Scale Up ◽  
Drug Resistant ◽  
Model Of Care ◽  
Drug Resistant Tuberculosis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Mdr Tb

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013–2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

scholarly journals Prevalence and factors associated with non-adherence to multi-drug resistant tuberculosis (MDR-TB) treatment at Mulago National Referral Hospital, Kampala, Uganda

2021 ◽  
Vol 21 (1) ◽  
pp. 238-47
Author(s):  
Charles Batte ◽  
Martha S Namusobya ◽  
Racheal Kirabo ◽  
John Mukisa ◽  
Susan Adakun ◽  
...  
Keyword(s):  
Mulago Hospital ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Factors Associated ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb ◽  
History Of ◽  
Previously Treated

Background: In Uganda, 12% of previously treated TB cases and 1.6% of new cases have MDR-TB and require specialized treatment and care. Adherence is crucial for improving MDR-TB treatment outcomes. There is paucity of information on the extent to which these patients adhere to treatment and what the drivers of non-adherence are. Methods: We conducted a cohort study using retrospectively collected routine program data for patients treated for MDR- TB between January 2012 – May 2016 at Mulago Hospital. We extracted anonymized data on non-adherence (missing 10% or more of DOT), socio-economic, demographic, and treatment characteristics of the patients. All participants were sen- sitive to MDR-TB drugs after second line Drug Susceptible Testing (DST) at entry into the study. Factors associated with non-adherence to MDR-TB treatment were determined using generalized linear models for the binomial family with log link and robust standard errors. We considered a p- value less than 0.05 as statistically significant. Results: The records of 227 MDR- TB patients met the inclusion criteria, 39.4% of whom were female, 32.6% aged be- tween 25 – 34 years, and 54.6% living with HIV/AIDS. About 11.9% of the patients were non-adherent. The main driver for non-adherence was history of previous DR-TB treatment; previously treated DR-TB patients were 3.46 (Adjusted prev- alence ratio: 3.46, 95 % CI: 1.68 - 7.14) times more likely to be non-adherent. Conclusion: One in 10 MDR-TB patients treated at Mulago hospital is non-adherent to treatment. History of previous DR- TB treatment was significantly associated with non-adherence in this study. MDR-TB program should strengthen adherence counselling, strengthen DST surveillance, and close monitoring for previously treated DR-TB patients. Keywords: Non-adherence; multi-drug resistant tuberculosis; treatment.

scholarly journals Barriers to Directly Observed Treatment for Multi Drug Resistant Tuberculosis Patients in Nepal - Qualitative Study

2018 ◽  
Vol 16 (1) ◽  
pp. 6-18
Author(s):  
R.P. Bichha ◽  
K.B. Karki ◽  
K.K. Jha ◽  
V.S. Salhotra ◽  
A.P. Weerakoon
Keyword(s):  
Qualitative Study ◽  
Health Workers ◽  
Previous History ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Major Barrier ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis ◽  
Mdr Tb

Introduction: To prevent the multi drug resistant tuberculosis (MDR-TB) is important to adhere long duration of drug regimen. There are many factors or barriers that are likely to affect adherence to the long treatment regimen. Objectives: To find out the barriers for adherence to MDR –TB treatment. Methods: The study was conducted as an institutional based qualitative study, using a convenient sampling technique. Data was collected from 50 current MDR-TB patients by trained field health workers using semi structured interviewer administered questionnaire in all regions in Nepal. Twenty five focus group discussions (FGD) were also conducted with MDR-TB patients, cured MDR-TB patients, DOTS Committee Members, health workers and close relatives of MDR-TB patients to supplement the findings. Results: Out of 50 respondents 19 were females and 31 were males. Their age varied from 22 years to 61 years. Majority of patients had a previous history of irregular TB treatment. Forty out of fifty patients (80%) were living in either rented houses or hostels (in Mid Western Region). Knowledge about TB and MDR-TB was satisfactory in majority of participants in both studies. Majority of participants were satisfied with facilities and services provided by MDR-TB clinics. There is a very little stigma associated with MDR-TB in Nepal. FGD revealed the onset of MDR-TB was attributed to causes such as smoking, alcohol abuse, poor nutrition, and contact with TB patients. Lack of money to go to health facility daily for treatment was reported as major barriers to adhere to MDR-TB treatment. Conclusion: Financial constraints were the major barrier for these patients. To sustain proper MDRTB programme, Government of Nepal and other organization should provide social support to these patients.  

Exploring patient-provider factors for risk of developing Multi-drug Resistance Tuberculosis in Southern Ethiopia: Qualitative Operation Research (Preprint)

2019 ◽  
Author(s):  
Yitagesu Habtu ◽  
Tesema Bereku ◽  
Girma Alemu ◽  
Ermias Abera
Keyword(s):  
Phenomenological Study ◽  
Treatment Success ◽  
World Health ◽  
Multi Drug Resistance ◽  
Southern Ethiopia ◽  
Drug Resistant ◽  
Related Factors ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multi Drug Resistant Tuberculosis

BACKGROUND Ethiopia is one of among thirty high burden countries of multi-drug resistant tuberculosis (MDR-TB) in the regions of world health organization. Contextual evidence on the emergence of the disease is limited at a program level. OBJECTIVE The aim of the study is to explore patient-provider factors that may facilitate the emergence of multi-drug resistant tuberculosis. METHODS We used a phenomenological study design of qualitative approach from June to July, 2015. We conducted ten in-depth interviews and 4 focus group discussions with purposely selected patients and providers. We designed and used an interview guide to collect data. Verbatim transcribes were exported to open code 3.4 for emerging thematic analysis. Domain summaries were used to support core interpretation. RESULTS The study explored patient-provider factors facilitating the emergence of multi-drug resistant tuberculosis. These factors as underlying, health system and patient-related factors. Especially, the a shows conflicting finding between having a history of discontinuing drug-susceptible tuberculosis and emergence of multi-drug resistant tuberculosis. CONCLUSIONS The patient-provider factors may result in poor early case identification, adherence to and treatment success in drug sensitive or multi-drug resistant tuberculosis. Our study implies the need for awareness creation about multi-drug resistant tuberculosis for patients and further familiarization for providers. This study also shows that patients developed multi-drug resistant tuberculosis though they had never discontinued their drug-susceptible tuberculosis treatment. Therefore, further studies may require for this discording finding.

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