scholarly journals Low-dose amikacin in the treatment of Multidrug-resistant Tuberculosis (MDR-TB)

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Natasha F. Sabur ◽  
Mantaj S. Brar ◽  
Lisa Wu ◽  
Sarah K. Brode
Keyword(s):  
Hearing Loss ◽  
Adverse Events ◽  
Low Dose ◽  
Multidrug Resistant ◽  
Significant Rise ◽  
World Health ◽  
Therapeutic Drug ◽  
Successful Treatment Outcome ◽  
Mdr Tb ◽  
Health Organization

Abstract Background The World Health Organization recommends intravenous amikacin for the treatment of MDR-TB at a dose of 15 mg/kg. However, higher doses are associated with significant toxicity. Methods Patients with MDR-TB treated at our institution receive amikacin at 8–10 mg/kg, with dose adjustment based on therapeutic drug monitoring. We conducted a retrospective cohort study of patients with MDR-TB who received amikacin between 2010 and 2016. Results Forty-nine patients were included in the study. The median starting dose of amikacin was 8.9 mg/kg (IQR 8, 10), and target therapeutic drug levels were achieved at a median of 12 days (IQR 5, 26). The median duration of amikacin treatment was 7.2 months (IQR 5.7, 8), and median time to sputum culture conversion was 1 month (IQR 1,2). Six patients (12.2%) experienced hearing loss based on formal audiometry testing (95% CI 4.6–24.8%); 22.2% had subjective hearing loss (95% CI 11.2–37.1%) and 31.9% subjective tinnitus (95% CI 19.1–47.1%). Ten patients (23%) had a significant rise in serum creatinine (95% CI 11.8–38.6%), but only 5 patients had a GFR < 60 at treatment completion. 84% of patients had a successful treatment outcome (95% CI 84–99%). Conclusions Low dose amikacin is associated with relatively low rates of aminoglycoside-related adverse events. We hypothesize that low-dose amikacin can be used as a safe and effective treatment for MDR-TB in situations where an adequate regimen cannot be constructed with Group A and B drugs, and where careful monitoring for adverse events is feasible.

scholarly journals Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

2019 ◽  
Vol 9 (1) ◽  
pp. 55 ◽  
Author(s):  
Arnaud Trébucq ◽  
Tom Decroo ◽  
Armand Van Deun ◽  
Alberto Piubello ◽  
Chen-Yuan Chiang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Low Income ◽  
Essential Medicine ◽  
Multidrug Resistant ◽  
World Health ◽  
Low Income Countries ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization

About ten years ago, the first results of the so-called “Bangladesh regimen”, a short regimen lasting nine months instead of 20 months, revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment. Similar short regimens were studied in different settings, relying for their efficacy on a later generation fluoroquinolone, either gatifloxacin, moxifloxacin, or levofloxacin. We review the published material on short MDR-TB regimens, describe their different compositions, their results in national tuberculosis programs in middle- and low-income countries, the risk of acquiring resistance to fluoroquinolone, and the occurrence of adverse events. With over 80% success, the regimen performs much better than longer regimens (usually around 50%). Monitoring of adverse events allows adapting its composition to prevent severe adverse events such as deafness. We discuss the current applicability and usefulness of the short injectable-containing regimen given the 2019 recommendation of the World Health Organization (WHO) for a new long all-oral regimen. We conclude that the most effective fluoroquinolone is gatifloxacin, currently not listed as an essential medicine by WHO. It is a priority to restore its status as an essential medicine.

Multidisciplinary advisory teams to manage multidrug-resistant tuberculosis: the example of the French Consilium

2019 ◽  
Vol 23 (10) ◽  
pp. 1050-1054
Author(s):  
L. Guglielmetti ◽  
J. Jaffré ◽  
C. Bernard ◽  
F. Brossier ◽  
N. El Helali ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Advisory Committees ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization

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.

scholarly journals Multidrug-resistant tuberculosis infection and disease in children: a review of new and repurposed drugs

2019 ◽  
Vol 6 ◽  
pp. 204993611986473 ◽  
Author(s):  
Julie Huynh ◽  
Ben J. Marais
Keyword(s):  
Clinical Care ◽  
Multidrug Resistant ◽  
World Health ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Resource Limited ◽  
Prevention And Treatment ◽  
Mdr Tb ◽  
Repurposed Drugs ◽  
Health Organization

The World Health Organization estimates that 10 million new cases of tuberculosis (TB) occurred worldwide in 2017, of which 600,000 were rifampicin or multidrug-resistant (RR/MDR) TB. Modelling estimates suggest that 32,000 new cases of MDR-TB occur in children annually, but only a fraction of these are correctly diagnosed and treated. Accurately diagnosing TB in children, who usually have paucibacillary disease, and implementing effective TB prevention and treatment programmes in resource-limited settings remain major challenges. In light of the underappreciated RR/MDR-TB burden in children, and the lack of paediatric data on newer drugs for TB prevention and treatment, we present an overview of new and repurposed TB drugs, describing the available evidence for safety and efficacy in children to assist clinical care and decision-making.

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 Detection of a novel mutation G511T in the 530 loop in 16S rRNA in multi drugs resistant Mycobacterium tuberculosis isolated from Sudanese patients

2018 ◽  
Author(s):  
Yousif Mohammed Alfatih ◽  
Abeer Babiker Idris ◽  
Hadeel Gassim Hassan ◽  
Eman O M Nour ◽  
Nihad M A Elhaj ◽  
...  
Keyword(s):  
16S Rrna ◽  
Molecular Mechanisms ◽  
Novel Mutation ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
World Health ◽  
Bacterial Disease ◽  
Global Public Health ◽  
Mdr Tb ◽  
Health Organization

Background: Tuberculosis (TB) is a bacterial disease considered as a global public health emergency by the World Health Organization (WHO) since 1993. In Sudan, MDR-TB represents a growing threat and one of the most important challenges that faced national tuberculosis program to establish a comprehensive multidrug-resistant tuberculosis management system. Objective: To characterize the diversity and frequency of mutations in Sudanese MDR-TB strains isolated from Wad Madani, Al-Gadarif and Khartoum using 16S rRNA and phylogeny approach. Material and Methods: A total of 60 MDR-TB isolates from Wad-Madani, Al-Gadarif and Khartoum were tested with molecular LPA (Genotype MTBDR plus) and GeneXpert MTB/RIF assay and Spoligotyping to confirm their resistance to RIF and INH. Sequencing and phylogenetic analysis was carried out using in silico tools. Result: This study revealed the circulation of different Sudanese MDR-TB strains isolated from Wad Madani and Al-Gadarif belonging to two distinct common ancestors. Two isolates from Wad Madani (isolate3 and isolate11) found in one main group which characterized by a novel mutation G511T in the 530 loop. Conclusion: The recurrence of C217A mutation in Wad Madani (isolate11) indicates the spread of this mutation in Sudanese MDR-TB strains and the diversity of this inheritance leading to generate new G511T novel mutation. So, understanding the molecular characterization of resistance mechanisms in MD-TB can facilitate the early detection of resistance, the choice of appropriate treatment and ultimately the management of MD-TB transmission. Bioinformatics approaches provide helpful tools for analyzing molecular mechanisms of resistance in pathogens.

scholarly journals Regimens to treat multidrug-resistant tuberculosis: past, present and future perspectives

2019 ◽  
Vol 28 (152) ◽  
pp. 190035 ◽  
Author(s):  
Emanuele Pontali ◽  
Mario C. Raviglione ◽  
Giovanni Battista Migliori
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
World Health ◽  
Drug Resistant ◽  
Optimal Outcomes ◽  
Resistant Tuberculosis ◽  
Prolonged Duration ◽  
Mdr Tb ◽  
Revised Definitions ◽  
Health Organization

Over the past few decades, treatment of multidrug-resistant (MDR)/extensively drug-resistant (XDR) tuberculosis (TB) has been challenging because of its prolonged duration (up to 20–24 months), toxicity, costs and sub-optimal outcomes.After over 40 years of neglect, two new drugs (bedaquiline and delamanid) have been made available to manage difficult-to-treat MDR-/XDR-TB cases. World Health Organization (WHO) guidelines published in March 2019 endorsed the possibility of treating MDR-TB patients with a full oral regimen, following previous guidelines published in 2016 which launched a shorter regimen lasting 9–10 months.The objectives of this article are to review the main achievements in MDR-TB treatment through the description of the existing WHO strategies, to discuss the main ongoing trials and to shed light on potential future scenarios and revised definitions necessary to manage drug-resistant TB.

scholarly journals Short-course treatment for multidrug-resistant tuberculosis: the STREAM trials

2016 ◽  
Vol 25 (139) ◽  
pp. 29-35 ◽  
Author(s):  
Riya Moodley ◽  
Thomas R. Godec
Keyword(s):  
Treatment Options ◽  
Standard Of Care ◽  
Multidrug Resistant ◽  
World Health ◽  
Efficacy And Safety ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Health Organization ◽  
Stage 1

Multidrug-resistant (MDR) tuberculosis (TB) is a threat to global TB control, as suboptimal and poorly tolerated treatment options have resulted in largely unfavourable outcomes for these patients. The last of six cohort studies conducted in Bangladesh which assessed a new shorter regimen using currently available TB drugs showed promising results and offered the possibility of a more acceptable and more effective regimen than the one recommended by the World Health Organization (WHO). The aims of stage 1 of the STREAM (Evaluation of a Standardised Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis) trial are to evaluate the efficacy and safety of this regimen, compared to the current WHO-recommended standard of care. Stage 2 evaluates two new bedaquiline-containing regimens: one an all-oral regimen and the second a further shortened and simplified version of the stage 1 study regimen, comparing the efficacy and safety of each to that of the stage 1 study regimen and also to the WHO-recommended standard of care. Success of the stage 1 study regimen would in all probability provide a new standard of care for MDR-TB patients, while positive results from the bedaquiline-containing regimens in stage 2 may allow for even greater progress in the management of this difficult population.

scholarly journals Emergence of bedaquiline-resistance in a high-burden country of tuberculosis

2021 ◽  
pp. 2100621
Author(s):  
Elena Chesov ◽  
Dumitru Chesov ◽  
Florian P. Maurer ◽  
Sönke Andres ◽  
Christian Utpatel ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Multidrug Resistant ◽  
World Health ◽  
Cross Sectional ◽  
Treatment Regimens ◽  
Cavitary Disease ◽  
Mdr Tb ◽  
The Republic ◽  
Health Organization

RationaleBedaquiline has been classified as a Group A drug for the treatment of multidrug-resistant tuberculosis (MDR-TB) by the World Health Organization, however globally emerging resistance threatens the effectivity of novel MDR-TB treatment regimens.ObjectivesWe analysed pre-existing and emerging bedaquiline resistance in bedaquiline-based MDR-TB therapies, and risk factors associated with treatment failure and death.MethodsIn a cross-sectional cohort study, we employed patient data, whole genome sequencing (WGS) and phenotyping of Mycobacterium tuberculosis complex (MTBC) isolates. We could retrieve baseline isolates from 30.5% (62/203) of all MDR-TB patients who received bedaquiline between 2016 and 2018 in the Republic of Moldova. This includes 26 patients for whom we could also retrieve a follow-up isolate.Measurements and Main ResultsAt baseline, all MTBC isolates were susceptible to bedaquiline. Among 26 patients with available baseline and follow-up isolates, 4/26 (15.3%) patients harbored strains which acquired bedaquiline resistance under therapy, while 1/26 (3.8%) patients was re-infected with a second bedaquiline resistant strain. Treatment failure and death were associated with cavitary disease (p=0.011), and any additional drug prescribed in the bedaquiline containing regimen with WGS-predicted resistance at baseline (p=0.012, OR 1.92 per unit increase, 95%CI 1.15–3.21).ConclusionsMDR-TB treatments based on bedaquiline require a functional background regimen to achieve high cure rates and to prevent the evolution of bedaquiline resistance. Novel MDR-TB therapies with bedaquiline require timely and comprehensive drug resistance monitoring.

scholarly journals Glycated hemoglobin screening identifies patients admitted for retreatment of tuberculosis at risk for diabetes in Tanzania

2016 ◽  
Vol 10 (04) ◽  
pp. 423-426 ◽  
Author(s):  
Margaretha L. Sariko ◽  
Stellah G. Mpagama ◽  
Jean Gratz ◽  
Riziki Kisonga ◽  
Queen Saidi ◽  
...  
Keyword(s):  
Glycated Hemoglobin ◽  
Multidrug Resistant ◽  
Referral Hospital ◽  
World Health ◽  
Tb Treatment ◽  
Number Needed To Screen ◽  
Resource Limited ◽  
Northern Tanzania ◽  
Mdr Tb ◽  
Health Organization

Introduction: World Health Organization recommendations of bidirectional screening for tuberculosis (TB) and diabetes have been met with varying levels of uptake by national TB programs in resource-limited settings. Methodology: Kibong’oto Infectious Diseases Hospital (KIDH) is a referral hospital for TB from northern Tanzania, and the national referral hospital for multidrug-resistant (MDR)-TB. Glycated hemoglobin (HgbA1c) testing was done on patients admitted to KIDH for newly diagnosed TB, retreatment TB, and MDR-TB, to determine the point prevalence of diabetes (HgbA1c ≥ 6.5%) and prediabetes (HgbA1c 5.7%–6.4%). Results: Of 148 patients hospitalized at KIDH over a single week, 59 (38%) had no prior TB treatment, 22 (15%) were retreatment cases, and 69 (47%) had MDR-TB. Only 3 (2%) had a known history of diabetes. A total of 144 (97%) had successful screening, of which 110 (77%) had an HgbA1c ≤ 5.6%, 28 (19%) had ≥ 5.7 < 6.5, and 6 (4%) had ≥ 6.5. Comparing subjects with prediabetes or diabetes to those with normal A1c levels, retreatment patients were significantly more likely to have a A1c ≥ 5.7% (odds ratio: 3.2, 95% CI: 1.2–9.0; p = 0.02) compared to those without prior TB treatment. No retreatment case was a known diabetic, thus the number needed to screen to diagnose one new case of diabetes among retreatment cases was 11. Conclusions: Diabetes prevalence by HgbA1c was less common than expected, but higher HgA1c values were significantly more frequent among retreatment cases, allowing for a rational, resource-conscious screening approach.

scholarly journals Evaluation of the GenoType MTBDRplusand MTBDRslfor the detection of drug-resistantMycobacterium tuberculosison isolates from Beijing, China

2018 ◽  
Author(s):  
Jiyong Jian ◽  
Xinyu Yang ◽  
Jun Yang ◽  
Liang Chen
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
World Health ◽  
Adequate Treatment ◽  
Extreme Drug Resistance ◽  
Mdr Tb ◽  
Health Organization ◽  
Beijing China ◽  
Timely Treatment

ABSTRACTThe incidence of tuberculosis (TB) and especially multidrug-resistant TB (MDR) and extreme drug resistance (XDR-TB) continue to increase alarmingly worldwide and reliable and fast diagnosis of MDR-TB and XDR-TB is essential for the adequate treatment of patients. So molecular line probe assays (LPAs) for detection of MDR-TB and XDR-TB have been endorsed by the World Health Organization (WHO). We analyzed 96 isolates from Beijing comparing culture-based drug susceptibility testing (DST) to LPAs detecting rifampicin (RFP), isoniazid (INH), and levofloxacin (LFX), amikacin (AM), capreomycin (CMP), ethambutol (EMB) resistance. Compared to phenotypic DST, the GenoType MTBDRplusand MTBDRslshowed a sensitivity of 98.7% and a specificity of 88.9% for detection of RFP resistance, 82.1% and 94.4% for INH, 89.7% and 94.4% for LFX, 60.0% and 98.7% for AM/CPM, 57.5% and 98.2% for EMB, respectively. The sensitivity and specificity of LPAs for MDR-TB and XDR-TB were 80.8%, 100% and 50.0%, 97.6%. Mutations in codon S531L of therpoBgene and S315T1 ofKatGgene were dominated in MDR-TB strains. The most frequently observed mutations were in codon A90V of thegyrAgene, A1401G of therrsgene and M306V of theembBgene, according to the MTBDRslresults. Our study showed that, in combination to phenotypic DST, application of the LPAs might be an efficient and reliable supplementary DST assay for rapid susceptibility screening of MDR-TB and XDR-TB. Using LPAs in high MDR/XDR burden countries allows for appropriate and timely treatment, which will reduce transmission rates, morbidity and improve treatment outcomes in patients.

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