scholarly journals Risk of hearing loss among multidrug-resistant tuberculosis patients according to cumulative aminoglycoside dose

2020 ◽  
Vol 24 (1) ◽  
pp. 65-72 ◽  
Author(s):  
H. Hong ◽  
D. W. Dowdy ◽  
K. E. Dooley ◽  
H. W. Francis ◽  
C. Budhathoki ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Dose Group ◽  
Low Dose ◽  
Multidrug Resistant ◽  
Prognostic Impact ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Increased Risk ◽  
Mdr Tb ◽  
The Impact

SETTING: The ototoxic effects of aminoglycosides (AGs) lead to permanent hearing loss, which is one of the devastating consequences of multidrug-resistant tuberculosis (MDR-TB) treatment. As AG ototoxicity is dose-dependent, the impact of a surrogate measure of AG exposure on AG-induced hearing loss warrants close attention for settings with limited therapeutic drug monitoring.OBJECTIVE: To explore the prognostic impact of cumulative AG dose on AG ototoxicity in patients following initiation of AG-containing treatment for MDR-TB.DESIGN: This prospective cohort study was nested within an ongoing cluster-randomized trial of nurse case management intervention across 10 MDR-TB hospitals in South Africa.RESULTS: The adjusted hazard of AG regimen modification due to ototoxicity in the high-dose group (≥75 mg/kg/week) was 1.33 times higher than in the low-dose group (<75 mg/kg/week, 95%CI 1.09–1.64). The adjusted hazard of developing audiometric hearing loss was 1.34 times higher than in the low-dose group (95%CI 1.01–1.77). Pre-existing hearing loss (adjusted hazard ratio [aHR] 1.71, 95%CI 1.29–2.26) and age (aHR 1.16 per 10 years of age, 95%CI 1.01–1.33) were also associated with an increased risk of hearing loss.CONCLUSION: MDR-TB patients with high AG dose, advanced age and pre-existing hearing loss have a significantly higher risk of AG-induced hearing loss. Those at high risk may be candidates for more frequent monitoring or AG-sparing regimens.

scholarly journals Adverse Effects and Choice between the Injectable Agents Amikacin and Capreomycin in Multidrug-Resistant Tuberculosis

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Amber Arnold ◽  
Graham S. Cooke ◽  
Onn Min Kon ◽  
Martin Dedicoat ◽  
Marc Lipman ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Adverse Effects ◽  
Total Duration ◽  
Multidrug Resistant ◽  
World Health ◽  
Fluoroquinolone Resistance ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Number Of Patients ◽  
Mdr Tb

ABSTRACT The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; n = 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n = 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; n = 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) (P = 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fifty-five percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; P = 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of >1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent.

scholarly journals Assessing the impacts of short-course multidrug-resistant tuberculosis treatment in the Southeast Asia Region using a mathematical modeling approach

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0248846
Author(s):  
Win Min Han ◽  
Wiriya Mahikul ◽  
Thomas Pouplin ◽  
Saranath Lawpoolsri ◽  
Lisa J. White ◽  
...  
Keyword(s):  
Southeast Asia ◽  
Treatment Initiation ◽  
Multidrug Resistant ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Short Course ◽  
Mdr Tb ◽  
The Impact

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.

scholarly journals Impact of multidrug-resistant tuberculosis and its medications on adverse maternal and perinatal outcomes: protocol for a systematic review and meta-analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. e034821 ◽  
Author(s):  
Kefyalew Addis Alene ◽  
Akilew Awoke Adane ◽  
Alemken Jegnie
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Perinatal Outcomes ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Impact

IntroductionMultidrug-resistant tuberculosis (MDR-TB) is a common public health problem affecting pregnant women. However, the impact of MDR-TB and its medication on pregnancy and perinatal outcomes has been poorly understood and inconsistently reported. Therefore, using the available literature, we aim to determine whether MDR-TB and its medications during pregnancy impact maternal and perinatal outcomes.Methods and analysisThis systematic review and meta-analysis will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Systematic searches will be conducted in PubMed, Scopus and Web of Science on 10 February 2020 for studies that reported adverse maternal and perinatal outcomes due to MDR-TB and/or its medication. The search will be performed without language and time restrictions. Adverse birth outcomes include miscarriage or abortion, stillbirth, preterm birth, low birth weight, small and large for gestational age, and neonatal death. Two independent reviewers will screen search records, extract data and assess the quality of the studies. The Newcastle-Ottawa Quality Assessment Scale will be used to assess the methodological quality of the included studies. In addition to a narrative synthesis, a random-effects meta-analysis will be conducted when sufficient data are available. I2 statistics will be used to assess the heterogeneity between studies.Ethics and disseminationAs it will be a systematic review and meta-analysis based on previously published evidence, there will be no requirement for ethical approval. Findings will be published in a peer-reviewed journal and will be presented at various conferences.

scholarly journals Multidrug-Resistant Tuberculosis and Its Association with Adrenal Insufficiency: Assessment with the Low-Dose ACTH Stimulation Test

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
René Rodríguez-Gutiérrez ◽  
Adrian Rendon ◽  
Maximiliano Barrera-Sánchez ◽  
Kevin Erick Gabriel Carlos-Reyna ◽  
Neri Alejandro Álvarez-Villalobos ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Low Dose ◽  
Multidrug Resistant ◽  
Stimulation Test ◽  
Acth Stimulation Test ◽  
Acth Stimulation ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Antituberculosis Treatment ◽  
Mdr Tb

Background. Multidrug-resistant tuberculosis (MDR-TB) is a major public health care concern that affects the life of millions of people around the world. The association of tuberculosis and adrenal insufficiency is well known; however, it is thought to be less prevalent every time. A spike in TB incidence and a lack of evidence of this association in patients with MDR-TB call for reassessment of an illness (adrenal dysfunction) that if not diagnosed could seriously jeopardize patients’ health.Objective. To determine the prevalence of adrenocortical insufficiency in patients with MDR-TB using the low-dose (1 μg) ACTH stimulation test at baseline and at 6–12 months of follow-up after antituberculosis treatment and culture conversion.Methods. A total of 48 men or women, aged ≥18 years (HIV-negative patients diagnosed with pulmonary MDR-TB) were included in this prospective observational study. Blood samples for serum cortisol were taken at baseline and 30 and 60 minutes after 1 μg ACTH stimulation at our tertiary level university hospital before and after antituberculosis treatment.Results. Forty-seven percent of subjects had primary MDR-TB; 43.8% had type 2 diabetes; none were HIV-positive. We found at enrollment 2 cases (4.2%) of adrenal insufficiency taking 500 nmol/L as the standard cutoff point value and 4 cases (8.3%) alternatively, using 550 nmol/L. After antituberculosis intensive phase drug-treatment and a negative mycobacterial culture (10.2±3.6months) adrenocortical function was restored in all cases.Conclusions. In patients with MDR-TB, using the low-dose ACTH stimulation test, a low prevalence of mild adrenal insufficiency was observed. After antituberculosis treatment adrenal function was restored in all cases. Given the increasing and worrying epidemic of MDR-TB these findings have important clinical implications that may help clinicians and patients make better decisions when deciding to test for adrenocortical dysfunction or treat insufficient stimulated cortisol levels in the setting of MDR-TB.

Effect of Global Fund financial support for patients with multidrug-resistant tuberculosis

2020 ◽  
Vol 24 (7) ◽  
pp. 686-693 ◽  
Author(s):  
T. Watthananukul ◽  
T. Liabsuetrakul ◽  
P. Pungrassami ◽  
V. Chongsuvivatwong
Keyword(s):  
Financial Support ◽  
Global Fund ◽  
Positive Impact ◽  
Multidrug Resistant ◽  
Drug Adherence ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Significant Difference ◽  
Mdr Tb ◽  
The Impact

SETTING: The Global Fund provides financial support for patients with multidrug-resistant tuberculosis (MDR-TB), patients' families and hospitals providing services for these patients in Thailand, but the impact of this support has not been evaluated.OBJECTIVE: To assess the impact of Global Fund financial support on drug adherence, out-of-pocket (OOP) payments, sputum culture conversion and the perception of the usefulness of this support.DESIGN: A retrospective cohort study was conducted in eight provincial hospitals with and without financial support in four regions of Thailand. MDR-TB patients aged ≥15 years registered in 2015–2016 who received treatment at these hospitals for at least 6 months were included.RESULTS: There was no significant difference in drug adherence rates. The OOP payments during treatment were significantly lower in patients who received financial support (P < 0.001). Although the supported group had higher positive culture rates at the beginning of treatment, sputum converted at a faster rate than for the unsupported group (P = 0.034). More than 80% of both groups perceived financial support as being useful, leading to faster diagnosis and improving follow-up compliance.CONCLUSION: Financial support for MDR-TB patients has a positive impact on treatment and should be continued.

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

2021 ◽  
pp. 2101925
Author(s):  
Xubin Zheng ◽  
Lina Davies Forsman ◽  
Ziwei Bao ◽  
Yan Xie ◽  
Zhu Ning ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Multidrug Resistant ◽  
Target Attainment ◽  
Cart Analysis ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
The Impact ◽  
Culture Conversion

BackgroundUnderstanding the impact of drug exposure and susceptibility on treatment response of multidrug-resistant tuberculosis (MDR-TB) will help to optimize treatment. This study aimed to investigate the association between drug exposure, susceptibility and response to MDR-TB treatment.MethodsDrug exposure and susceptibility for second-line drugs were measured for patients with MDR-TB. Multivariate analysis was applied to investigate the impact of drug exposure and susceptibility on sputum culture conversion and treatment outcome. Probability of target attainment was evaluated. Random Forest and classification and regression tree (CART) analysis was used to identify key predictors and their clinical targets among patients on WHO-recommended regimens.ResultsDrug exposure and corresponding susceptibility were available for 197 patients with MDR-TB. Target attainment was highly variable ranging from 0% for ethambutol to 97% for linezolid, while patients with fluoroquinolones above targets had higher probability of two-month culture conversion (56.3% versus 28.6%, OR 2.91, 95% CI 1.42–5.94) and favourable outcome (88.8% versus 68.8%, OR 2.89, 95% CI 1.16–7.17). Higher exposure values of fluoroquinolones, linezolid and pyrazinamide were associated with earlier sputum culture conversion. CART analysis selected moxifloxacin AUC/MIC of 231 and linezolid AUC/MIC of 287 as best predictors for six-month culture conversion in patients receiving identical Group A-based regimen. These association were confirmed in multivariate analysis.ConclusionsOur findings indicated that target attainment of TB drugs is associated with response to treatment. The CART-derived thresholds may serve as targets for early dose adjustment in a future randomized controlled study to improve the MDR-TB treatment outcome.

scholarly journals The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Chathika K Weerasuriya ◽  
Rebecca C Harris ◽  
C Finn McQuaid ◽  
Fiammetta Bozzani ◽  
Yunzhou Ruan ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Cost Effective ◽  
Multidrug Resistant ◽  
Second Line ◽  
Second Line Therapy ◽  
China And India ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Line Therapy ◽  
Mdr Tb

Abstract Background Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. Methods We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027–2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. Results By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69–72) and 72% (UI: 70–74), and the PSI vaccine by 31% (UI: 30–32) and 44% (UI: 42–47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8–1.1) and 1.1 million (UI: 0.9–1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. Conclusions Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

PP581 Catastrophic Costs Of Multidrug-Resistant Tuberculosis: Estimation Based On The Cost Of Treatment In China

2020 ◽  
Vol 36 (S1) ◽  
pp. 43-43
Author(s):  
Lijun Shen ◽  
Shangshang Gu ◽  
Fan Zhang ◽  
Zhao Liu ◽  
Yuehua Liu
Keyword(s):  
Market Price ◽  
Multidrug Resistant ◽  
Policy Support ◽  
World Health ◽  
Chinese Patients ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Drug Affordability ◽  
The Cost

IntroductionChina bears a considerably high burden of multidrug-resistant tuberculosis (MDR-TB). Second-line anti-TB drugs are urgently needed yet domestic MDR-TB drugs are expensive and lack policy support. Patients’ living conditions are closely related to the drug affordability. The national TB prevention programs should play a critical role. The purpose of this study is to measure the cost of treating MDR-TB patients under different treatment schemes and price sources. The results of this study are expected to inform the relevant drug protection policies and provide inputs for further cost-effectiveness analyses.MethodsBased on the treatment plan of China's Multidrug-Resistant Pulmonary Tuberculosis Clinical Path (2012 edition) and the World Health Organization (WHO) Drug-Resistant Tuberculosis Treatment Guide (2018 edition), the treatment costs of MDR-TB were measured under different scenarios. Catastrophic health expenditure was then calculated if the treatment cost exceeds 40 percent of the household's non-subsistence income. National, rural and disposable income per capita in 2018, were used to represent Chinese patients’ affordability.ResultsUnder varied treatment schemes and market price sources in China, the total costs for MDR-TB patients range from 19,401 to 126,703 CNY [2,853 to 18,633 USD] per person. Under current prices, all treatment schemes recommended by the WHO will incur catastrophic costs for Chinese MDR-TB patients. Significant differences were found between rural and urban areas as 52.8 percent of the treatment listed in the 2012 China Guideline would lead to catastrophic cost for rural patients but not urban ones.ConclusionsOur study concludes that the domestic drugs are more expensive than the international purchase price and the treatment of MDR-TB imposes substantial economic burden on patients, especially in the rural areas. The results of the study also indicate that it is urgent for the state to emphasize government responsibility and initiate centralized procurement for price negotiations to reduce the market price of MDR-TB drugs. The urban-rural gap should also be addressed in the design of future policies to ensure the drug affordability for all patients in need.

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