Impact of bedaquiline on treatment outcomes of multidrug-resistant tuberculosis in a high-burden country

2020 ◽  
pp. 2002544
Author(s):  
Dumitru Chesov ◽  
Jan Heyckendorf ◽  
Sofia Alexandru ◽  
Ana Donica ◽  
Elena Chesov ◽  
...  

Evaluation of novel anti-tuberculosis (TB) medicines for the treatment of multidrug-resistant (MDR)-TB continues to be of high interest on the TB research agenda. We assessed treatment outcomes in patients with pulmonary MDR-TB who received bedaquiline containing treatment regimens in the Republic of Moldova, a high-burden country of MDR-TB.MethodWe systematically analysed the “SIMETB” national electronic TB database in the Republic of Moldova and performed a retrospective propensity score matched comparison of treatment outcomes in a cohort of patients with MDR-TB who started treatment during 2016–2018 with a bedaquiline-containing regimen (bedaquiline cohort) and a cohort of patients treated without bedaquiline (non-bedaquiline cohort).ResultsFollowing propensity score matching, 114 patients were assigned to each cohort of MDR-TB patients. Patients in the bedaquiline cohort had a higher 6 month sputum culture conversion rate than those in the non-bedaquiline cohort, (66.7% versus 40.3%, p<0.001). Patients under bedaquiline containing regimens had a higher cure rate assessed by both WHO and TBNET definitions (55.3% versus 24.6%, p=0.001 and 43.5% versus 19.6% p=0.004, correspondingly), as well, a lower mortality rate (8.8% versus 20.2%, p<0.001, by WHO and 10.9% versus 25.2%, p=0.01, by TBNET). In patients who previously failed on MDR-TB treatment, more than 40% of patients achieved cure with a bedaquiline-containing regimen.ConclusionsBedaquiline-based MDR-TB treatment regimens result in better disease resolution when compared to bedaquiline-sparing MDR-TB treatment regimens under programmatic conditions in a country with a high-burden of MDR-TB.

2019 ◽  
Vol 23 (10) ◽  
pp. 1050-1054
Author(s):  
L. Guglielmetti ◽  
J. Jaffré ◽  
C. Bernard ◽  
F. Brossier ◽  
N. El Helali ◽  
...  

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.


2020 ◽  
Vol 24 (5) ◽  
pp. 485-491
Author(s):  
D. Butov ◽  
C. Lange ◽  
J. Heyckendorf ◽  
I. Kalmykova ◽  
T. Butova ◽  
...  

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.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248846
Author(s):  
Win Min Han ◽  
Wiriya Mahikul ◽  
Thomas Pouplin ◽  
Saranath Lawpoolsri ◽  
Lisa J. White ◽  
...  

This study aimed to predict the impacts of shorter duration treatment regimens for multidrug-resistant tuberculosis (MDR-TB) on both MDR-TB percentage among new cases and overall MDR-TB cases in the WHO Southeast Asia Region. A deterministic compartmental model was constructed to describe both the transmission of TB and the MDR-TB situation in the Southeast Asia region. The population-level impacts of short-course treatment regimens were compared with the impacts of conventional regimens. Multi-way analysis was used to evaluate the impact by varying programmatic factors (eligibility for short-course MDR-TB treatment, treatment initiation, and drug susceptibility test (DST) coverage). The model predicted that overall TB incidence will be reduced from 246 (95% credible intervals (CrI), 221–275) per 100,000 population in 2020 to 239 (95% CrI, 215–267) per 100,000 population in 2035, with a modest reduction of 2.8% (95% CrI, 2.7%–2.9%). Despite the slight reduction in overall TB infections, the model predicted that the MDR-TB percentage among newly notified TB infections will remain steady, with 2.4% (95% CrI, 2.1–2.9) in 2020 and 2.5% (95% CrI, 2.3–3.1) in 2035, using conventional MDR-TB treatment. With the introduction of short-course regimens to treat MDR-TB, the development of resistance can be slowed by 38.6% (95% confidence intervals (CI), 35.9–41.3) reduction in MDR-TB case number, and 37.6% (95% CI, 34.9–40.3) reduction in MDR-TB percentage among new TB infections over the 30-year period compared with the baseline using the standard treatment regimen. The multi-way analysis showed eligibility for short-course treatment and treatment initiation greatly influenced the impacts of short-course treatment regimens on reductions in MDR-TB cases and percentage resistance among new infections. Policies which promote the expansion of short-course regimens and early MDR-TB treatment initiation should be considered along with other interventions to tackle antimicrobial resistance in the region.


2020 ◽  
Author(s):  
Le Hong Van ◽  
Phan Trieu Phu ◽  
Dao Nguyen Vinh ◽  
Vo Thanh Son ◽  
Nguyen Thi Hanh ◽  
...  

Abstract Background: Multidrug 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.Methods: This retrospective study included 2,266 patients who initiated MDR-TB treatment between 2011-2015 in HCMC. Treatment outcomes were available for 2,240 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.Results: Among 2,266 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 2011-2015. 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 1kg/m2 of BMI for patients with BMI<21).Conclusion: The number of patients diagnosed with MDR-TB in HCMC increased by almost a quarter between 2011-2015. Patients with HIV, high smear grade, malnutrition or a history of previous MDR-TB treatment are at greatest risk of poor treatment outcome.


PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0255357
Author(s):  
Nguyen Bao Ngoc ◽  
Hoa Vu Dinh ◽  
Nguyen Thi Thuy ◽  
Duong Van Quang ◽  
Cao Thi Thu Huyen ◽  
...  

Objective Management of multidrug-resistant tuberculosis (MDR-TB) is a significant challenge to the global healthcare system due to the complexity and long duration of the MDR-TB treatment. This study analyzed the safety of patients on longer injectable-based MDR-TB treatment regimens using active pharmacovigilance data. Method We conducted an observational, prospective study based on active pharmacovigilance within the national TB program. A total of 659 MDR-TB patients were enrolled and followed up at 9 TB- hospitals in 9 provinces of all 3 regions in Vietnam between 2014 and 2016. Patients received a treatment regimen (standardized or individualized) based on their drug susceptibility test result and their treatment history. Baseline and follow-up information was collected at the start and during treatment. Adverse events (AE) were defined and classified as serious adverse events (SAEs) or otherwise. Multivariate Cox regression following the Iterative Bayesian Model Averaging algorithm was performed to identify factors associated with AE occurrence. Results Out of 659 patients assessed, 71.3% experienced at least one AE, and 17.5% suffered at least one SAE. The most common AEs were gastrointestinal disorders (38.5%), arthralgia (34.7%), and psychiatric disorders (30.0%). The proportion of patients with nephrotoxicity and hearing loss or vestibular disorders were 7.4% and 15.2%, respectively. 13.1% of patients required modifications or interruption of one or more drugs. In 77.7% of patients, treatment was completed successfully, while 9.3% lost to follow-up, in 3.0% treatment failed, and 7.4% died. Some significant risk factors for nephrotoxicity included diabetes mellitus (HR = 8.46 [1.91–37.42]), renal dysfunction (HR = 8.46 [1.91–37.42]), alcoholism (HR = 13.28 [5.04–34.99]), and a higher average daily dose of injectable drugs (HR = 1.28 [1.14–1.43]). Conclusion While a majority of patients on the longer injectable-based regimens experienced non-serious AEs during MDR-TB treatment, one in six patients experienced at least an SAE. Active TB drug-safety monitoring is useful to understand the safety of MDR-TB treatment and explore the risk factors for toxicity. All-oral, shorter MDR-TB regimens might be able to reduce the inconvenience, discomfort, and toxicity of such regimens and increase adherence and likelihood of successful completion.


2015 ◽  
Vol 59 (10) ◽  
pp. 6073-6079 ◽  
Author(s):  
Anthony J. Garcia-Prats ◽  
Heather R. Draper ◽  
Stephanie Thee ◽  
Kelly E. Dooley ◽  
Helen M. McIlleron ◽  
...  

ABSTRACTOfloxacin is widely used for the treatment of multidrug-resistant tuberculosis (MDR-TB). Data on its pharmacokinetics and safety in children are limited. It is not known whether the current internationally recommended pediatric dosage of 15 to 20 mg/kg of body weight achieves exposures reached in adults with tuberculosis after a standard 800-mg dose (adult median area under the concentration-time curve from 0 to 24 h [AUC0–24], 103 μg · h/ml). We assessed the pharmacokinetics and safety of ofloxacin in children <15 years old routinely receiving ofloxacin for MDR-TB treatment or preventive therapy. Plasma samples were collected predose and at 1, 2, 4, 8, and either 6 or 11 h after a 20-mg/kg dose. Pharmacokinetic parameters were calculated using noncompartmental analysis. Children with MDR-TB disease underwent long-term safety monitoring. Of 85 children (median age, 3.4 years), 11 (13%) were HIV infected, and of 79 children with evaluable data, 14 (18%) were underweight. The ofloxacin mean (range) maximum concentration (Cmax), AUC0–8, and half-life were 8.97 μg/ml (2.47 to 14.4), 44.2 μg · h/ml (12.1 to 75.8), and 3.49 h (1.89 to 6.95), respectively. The mean AUC0–24, estimated in 72 participants, was 66.7 μg · h/ml (range, 18.8 to 120.7). In multivariable analysis, AUC0–24was increased by 1.46 μg · h/ml for each 1-kg increase in body weight (95% confidence interval [CI], 0.44 to 2.47;P= 0.006); no other assessed variable contributed to the model. No grade 3 or 4 events at least possibly attributed to ofloxacin were observed. Ofloxacin was safe and well tolerated in children with MDR-TB, but exposures were well below reported adult values, suggesting that dosage modification may be required to optimize MDR-TB treatment regimens in children.


2019 ◽  
Vol 11 (6) ◽  
pp. 520-527 ◽  
Author(s):  
Edson Mollel ◽  
Isack Lekule ◽  
Lutgarde Lynen ◽  
Tom Decroo

Abstract Background During 2009–2013, Xpert MTB/RIF testing was decentralized in Tanzania. Standardized treatment of multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) was centralized at the Kibong’oto Infectious Diseases Hospital. Initially, Xpert MTB/RIF results were confirmed and complemented with phenotypic drug susceptibility testing before MDR-TB treatment was started. Since 2013, the decision to start MDR-TB treatment in patients with RR-TB relied on Xpert MTB/RIF results. Methods A retrospective cohort study of predictors of unsuccessful treatment outcomes (including death, lost to follow-up and treatment failure) was carried out. Results During the study period, 201 patients started MDR-TB treatment. The number of patients starting MDR-TB treatment increased over time. Out of 201 patients, 48 (23.9%) had an unsuccessful treatment outcome. The median time between sample collection and MDR-TB treatment initiation was reduced from 155 d (IQR 40–228) in the 2009–2012 period to 26 d (IQR 13–64) in 2013. Patients who started MDR-TB treatment in 2013 were more likely (adjusted OR 2.3; 95% CI 1.1–4.7; p=0.02) to have an unsuccessful treatment outcome. Conclusions Xpert MTB/RIF testing increased enrolment on MDR-TB treatment. Reliance on Xpert MTB/RIF results to start MDR-TB treatment reduced time to treatment. However, treatment outcomes did not improve.


2021 ◽  
Vol 91 (1) ◽  
Author(s):  
Valeriu Plesca ◽  
Ana Ciobanu ◽  
Yuliia Sereda ◽  
Andrei Dadu

The Republic of Moldova is among the 30 Rifampicin-Resistant and/or Multidrug-Resistant (RR/MDR) Tuberculosis (TB) high burden countries in the world. Despite free TB diagnostics and treatment, TB patients face substantial economic losses and this may impact overall treatment outcomes. We assessed if there is an association between TB-related catastrophic costs and TB treatment outcomes. We conducted a cohort study using data from patient records and a survey that quantified catastrophic costs among RR/MDR-TB affected households in the Republic of Moldova in 2016. We included adult patients (age ≥18 years) with RR/MDR-TB who had been in inpatient (intensive phase) or outpatient (continuous phase) treatment for at least 2 months. Unfavourable treatment outcome, such as failure, death or lost to follow-up, was the primary outcome variable. The definition of catastrophic TB-related costs followed the World Health Organisation (WHO) guidelines: costs due to TB ≥20% of annual household income. Log-binomial regression was used to assess association between the outcome and catastrophic TB-related costs adjusting for other socio-demographic, behavioural and clinical covariates.  In total 287 RR/MDR-TB patients (78% males, mean age 42 years) were included. Of them, 30% experienced catastrophic TB-related costs. Overall, one in five patients (21%) had unfavourable treatment outcome, such as treatment failure (5%), death (8%) or lost to follow-up (8%). The experience of catastrophic TB-related costs was not associated with unfavourable treatment outcome [adjusted relative risk (aRR)=0.88, 95% CI: 0.50–1.50]. Major factors independently associated with unfavourable TB treatment outcomes were poverty (aRR=2.07; 95% CI: 1.06-4.07), urban residence (aRR=1.99; 95% CI: 1.12-3.52) and positive HIV (Human Immunodeficiency Virus) status (aRR=2.61; 95% CI: 1.31-4.89). As a result, we failed to find an association between catastrophic costs and treatment outcomes of RR/MDR-TB patients in the Republic of Moldova. However, we found that patients from poor households and urban areas were twice more likely to achieve unfavourable TB treatment outcomes disregarding whether they experienced catastrophic costs or not. Also, TB/HIV patients and urban residents were identified as the most vulnerable groups with higher risk of unfavourable treatment outcome and TB-related costs.


2019 ◽  
Vol 13 (3) ◽  
Author(s):  
Noerfitri Noerfitri ◽  
R. Sutiawan ◽  
Tri Yunis Miko Wahyono ◽  
Pratiwi Ayuningtyas Hartono

Drug resistant TB patients had a greater risk of LTFU than drug-sensitive TB patients due to longer treatment duration. The aims of this study were to determine the influence of decentralization and type of patient to LTFU in MDR-TB patients in Indonesia. This study was conducted in May-June 2018 at Sub Directorate of TB - Ministry of Health of the Republic of Indonesia. The study design was retrospective cohort. Samples were taken in total sampling with a total of 961 patients. 86.3% of patients were decentralized. Based on the type, the patient consists of 35.17% relapse, 5.52% new, 13.94% after LTFU, 23.10% failure category 1, 20.29% failure category 2, 1.9 % other patients. In multivariate analysis revealed that decentralization reduced the probability of LTFU up to 46% (HR 0.54, 95% CI 0.35-0.84). For patient type, treatment after LTFU, failure category 2 and others increased the probability of LTFU by 50% (HR 2,02; 95% CI 1,18-3,45), 53% (HR 2,13; 95% CI 1,24-3,66), and 74% (HR 3,80; 95% CI 1,54-9,36) consecutively compared with the type of relapse patients (baseline). Health workers were suggested to spend more time in communicating, informing and educating about TB treatment and the benefits of decentralization to MDR-TB patients. Moreover, it is suggested to conduct patient type screening in the beginning of the treatment to be able to identify the risk of LTFU.


2018 ◽  
Vol 62 (4) ◽  
pp. e02259-17 ◽  
Author(s):  
Yong Chen ◽  
Zhengan Yuan ◽  
Xin Shen ◽  
Jie Wu ◽  
Zheyuan Wu ◽  
...  

ABSTRACT In high tuberculosis (TB)-burden countries such as China, the diagnosis of multidrug-resistant tuberculosis (MDR-TB) using conventional drug susceptibility testing (DST) takes months, making treatment delay inevitable. Poor outcomes of MDR-TB might be associated with delayed, even inappropriate, treatment. The purposes of this study were to investigate the time to MDR-TB treatment initiation and to assess the association between early treatment and treatment outcomes. Between April 2011 and December 2014, this population-based retrospective cohort study collected the demographic and clinical characteristics and the drug susceptibility profiles of all registered MDR-TB patients in Shanghai, China. The dates of TB and MDR-TB diagnoses, DST performance, and treatment initiation were extracted to calculate the times to treatment. In total, 284 of 346 MDR-TB patients were eligible for analysis, and 68.3% (194/284) had favored outcomes. The median time to treatment initiation from TB diagnosis was 172 days among those with favored outcomes and 190 days among those with poor outcomes. Treatments initiated within 60 days after performing DST (odds ratio [OR], 2.56; 95% confidence interval [CI], 1.22 to 5.36) and empirical treatments (OR, 2.09; 95% CI, 1.01 to 4.32) were positively associated with favored outcomes. Substantial delays to MDR-TB treatment were observed when conventional DST was used. Early treatment predicted favored outcomes. Rapid diagnostic methods should be scaled up and improvements should be made in patient management and information linkage to reduce treatment delay.


Sign in / Sign up

Export Citation Format

Share Document