scholarly journals Treatment of Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis in Children: The Role of Bedaquiline and Delamanid

2021 ◽  
Vol 9 (5) ◽  
pp. 1074
Author(s):  
Francesco Pecora ◽  
Giulia Dal Canto ◽  
Piero Veronese ◽  
Susanna Esposito
Keyword(s):  
Adverse Effects ◽  
Pediatric Population ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Drug Resistant ◽  
Standard Regimen ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb

Multidrug-resistant (MDR) tuberculosis (TB) has been emerging at an alarming rate over the last few years. It has been estimated that about 3% of all pediatric TB is MDR, meaning about 30,000 cases each year. Although most children with MDR-TB can be successfully treated, up to five years ago effective treatment was associated with a high incidence of severe adverse effects and patients with extensively drug-resistant (XDR) TB had limited treatment options and no standard regimen. The main objective of this manuscript is to discuss our present knowledge of the management of MDR- and XDR-TB in children, focusing on the characteristics and available evidence on the use of two promising new drugs: bedaquiline and delamanid. PubMed was used to search for all of the studies published up to November 2020 using key words such as “bedaquiline” and “delamanid” and “children” and “multidrug-resistant tuberculosis” and “extensively drug-resistant tuberculosis”. The search was limited to articles published in English and providing evidence-based data. Although data on pediatric population are limited and more studies are needed to confirm the efficacy and safety of bedaquiline and delamanid, their use in children with MDR-TB/XDR-TB appears to have good tolerability and efficacy. However, more evidence on these new anti-TB drugs is needed to better guide their use in children in order to design effective shorter regimens and reduce adverse effects, drug interactions, and therapeutic failure.

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 Emergence of Low-level Delamanid and Bedaquiline Resistance During Extremely Drug-resistant Tuberculosis Treatment

2019 ◽  
Vol 69 (7) ◽  
pp. 1229-1231 ◽  
Author(s):  
Silke Polsfuss ◽  
Sabine Hofmann-Thiel ◽  
Matthias Merker ◽  
David Krieger ◽  
Stefan Niemann ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
New Drugs ◽  
Tuberculosis Treatment ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Low Level ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant

Abstract Two new drugs, delamanid and bedaquiline, have recently been approved for treatment of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis. Here, we report a case of clofazimine, bedaquiline, and low-level delamanid resistances acquired during treatment of a patient with XDR tuberculosis.

scholarly journals Evolving rifampicin and isoniazid mono-resistance in a high multidrug-resistant and extensively drug-resistant tuberculosis region: a retrospective data analysis

BMJ Open ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. e031663
Author(s):  
Nomonde Ritta Mvelase ◽  
Yusentha Balakrishna ◽  
Keeren Lutchminarain ◽  
Koleka Mlisana
Keyword(s):  
South Africa ◽  
Diagnostic Algorithm ◽  
Multidrug Resistant ◽  
Continuous Phase ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Kwazulu Natal ◽  
Mdr Tb

ObjectivesSouth Africa ranks among the highest drug-resistant tuberculosis (DR-TB) burdened countries in the world. This study assessed the changes in resistance levels in culture confirmed Mycobacterium tuberculosis (MTB) in the highest burdened province of South Africa during a period where major changes in diagnostic algorithm were implemented.SettingThis study was conducted at the central academic laboratory of the KwaZulu-Natal province of South Africa.ParticipantsWe analysed data for all MTB cultures performed in the KwaZulu-Natal province between 2011 and 2014. The data were collected from the laboratory information system.ResultsOut of 88 559 drug susceptibility results analysed, 18 352 (20.7%) were resistant to rifampicin (RIF) and 19 190 (21.7%) showed resistance to isoniazid (INH). The proportion of rifampicin resistant cases that were mono-resistant increased from 15.3% in 2011 to 21.4% in 2014 while INH mono-resistance (IMR) showed a range between 13.8% and 21.1%. The multidrug-resistant tuberculosis (MDR-TB) rates increased from 18.8% to 23.9% and the proportion of MDR-TB cases that had extensively drug-resistant tuberculosis remained between 10.2% and 11.1%. Most drug resistance was found in females between the ages of 15 and 44 years and the northern districts bordering high MDR-TB regions had the highest MDR-TB rates.ConclusionOur findings show increasing RIF mono-resistance (RMR) and a substantial amount of IMR. This highlights a need for an initial test that detects resistance to both these drugs so as to avoid using RIF monotherapy during continuous phase of treatment in patients with IMR. Furthermore, addition of INH will benefit patients with RMR. Although DR-TB is widespread, HIV and migration influence its distribution; therefore, TB control strategies should include interventions that target these aspects.

scholarly journals EXTENSIVELY DRUG RESISTANT TUBERCULOSIS (XDR TB)

2019 ◽  
Vol 5 (2) ◽  
pp. 26
Author(s):  
Sarah Rahmayani Siregar
Keyword(s):  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Drug Susceptibility Testing ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Tuberculosis Programme ◽  
Mdr Tb ◽  
Directly Observed Treatment

Tuberkulosis adalah penyakit infeksi kronis menular yang masih merupakan masalah kesehatan masyarakat di dunia termasuk Indonesia. Tuberkulosis (TB) sebagian besar akan mengalami penyembuhan dengan pengobatan. Namun tidak semua penyakit TB sembuh dengan pengobatan. Hal ini disebabkan pengobatan dari TB yang belum terlaksana dengan baik sehingga dapat pula menyebabkan terjadinya resistensi terhadap Obat Anti Tuberkulosis (OAT), berupa Multidrug Resistant Tuberkulosis (MDR TB) dan Extensively Drug Resistant Tuberculosis (XDR TB). XDR TB adalah TB yang disebabkan oleh strain yang resistensi terhadap isoniazid dan rifampisin, disertai resisten terhadap salah satu fluorokuinolon dan salah satu dari tiga obat injeksi lini kedua (amikasin, kapreomisin atau kanamisin). XDR TB diperkenalkan tahun 2006 ketika terjadi epidemi yang sangat fatal di Afrika Selatan. XDR-TB dapat ditularkan melalui bakteri yang disebarkan oleh orang yang sudah terkena resistensi obat. Diagnosis XDR-TB ditegakkan dengan uji sensitiviti obat atau Drug Susceptibility Testing (DST), bukan sekedar berdasarkan gambaran foto toraks dan adanya faktor resiko yang ada pada seseorang. WHO telah merancang strategi Directly Observed Treatment Short Course (DOTS-Plus) untuk mengelola TB M/XDR di negara-negara miskin sumber daya. Revisi National Tuberculosis Programme (RNTCP) di bawah DOTS-Plus akan menggunakan rejimen pengobatan standar (STR) kategori IV, yang terdiri dari 6 obat (kanamisin, levofloxacin, etionamid, sikloserin, pirazinamid, dan etambutol) selama 6-9 bulan fase intensif dan 4 obat (levofloxacin, ethionamide, cycloserine, dan ethambutol) selama 18 bulan dari fase lanjutan. Penyembuhan tergantung pada tingkat resistensi obat, tingkat keparahan penyakit dan apakah sistem kekebalan pasien terganggu.

scholarly journals Issues of Tuberculosis Drug-Resistance in Kharkiv Region and in Ukraine

2019 ◽  
pp. 24-28
Author(s):  
O.S. Shevchenko ◽  
O.O. Pohorielova
Keyword(s):  
Drug Resistance ◽  
Statistical Processing ◽  
Multidrug Resistant ◽  
Study Data ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Microsoft Office

Background. Multidrug-resistant tuberculosis and extensively drug-resistant tuberculosis remain severe epidemic problems in the world. That’s why the purpose of our study was to investigate the dynamics of the incidence of multidrug-resistant and extensively drug-resistant tuberculosis, the structure of cases and the effectiveness of treatment in this category of patients in the Kharkiv region and in Ukraine. Materials and methods. To perform the study, data from reporting forms No. 4-2 (TB 07 – MDR TB), No. 8-6 (TB 08) and data from analytical and statistical reference books “Tuberculosis in Ukraine” were used. Statistical processing of information was carried out using Statistica 7.0, Microsoft Office Excel 2007. Results. We found a relatively consistently high incidence rate, prevalence of tuberculosis recurrences among patients with drug-resistant tuberculosis, an increase in the proportion of extensively-drug resistance in patients with treatment failure and interrupted treatment, and low effectiveness of treatment of multidrug-resistant and extensively drug-resistant tuberculosis in patients with repeated cases of treatment. Conclusions. The obtained data once again emphasizes the need for the selection of adequate schemes for antituberculosis chemotherapy and control of anti-tuberculosis drugs.

scholarly journals Multidrug-Resistant and Extensively Drug Resistant Tuberculosis in Kashmir, India

2009 ◽  
Vol 4 (01) ◽  
pp. 019-023 ◽  
Author(s):  
Bikram Singh Datta ◽  
Ghulam Hassan ◽  
Syed Manzoor Kadri ◽  
Waseem Qureshi ◽  
Mustadiq Ahmad Kamili ◽  
...  
Keyword(s):  
Tertiary Care ◽  
Hospital Setting ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Care Hospital ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb

Background: To study the profile of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in tertiary care hospital setting, representing almost the whole affected population in Kashmir valley of India. Methodology: A total of 910 cases of pulmonary tuberculosis were enrolled over four years. Among these, cases of MDR-TB and XDR-TB were meticulously studied for drug susceptibility, treatment, adverse effects profile and overall survival. Results: Fifty-two (5.7%) cases of MDR-TB were identified, among which eight (15.3%) were diagnosed as XDR-TB on the basis of drug susceptibility testing, using the prescribed definition. The cases were sensitive to 2, 3, 4, 5 and more than 5 drugs in almost equal proportions. Thirty-seven (71.1%) cases were successfully cured; eleven (21.1%) patients died; and only four (7.6%) cases defaulted, indicating overall satisfactory adherence to treatment. Conclusion: For effective treatment of MDR-TB and XDR-TB, early case detection, improved laboratory facilities, availability of appropriate treatment regimens, and financial assistance in resource-limited settings through effective political intervention are necessary for better patient adherence and overall cure.

scholarly journals Cycloserine for Treatment of Multidrug-Resistant Tuberculosis in China: A Retrospective Observational Study

2018 ◽  
Author(s):  
Yang Li ◽  
Fei Wang ◽  
Limin Wu ◽  
Min Zhu ◽  
Guiqing He ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
Observational Study ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Extensively Drug Resistant ◽  
Mdr Tb ◽  
Culture Conversion

AbstractObjectivesCycloserine is crucial in multidrug-resistant tuberculosis (MDR-TB) treatment. Although extensive research has been carried out on MDR-TB, most researchers have not treated cycloserine in much detail. Therefore, we evaluate the efficacy and safety of cycloserine and seek to clarify the role of cycloserine for treatment of simple MDR-TB, pre-extensively drug-resistant tuberculosis (pre-XDR-TB), and extensively drug-resistant tuberculosis (XDR-TB).Patients and methodsA retrospective observational study was performed in China. We determined the treatment outcome as the primary outcome for 144 cycloserine-treated and 181 cycloserine-nontreated patients according to the definitions of WHO. The proportion of patients with sputum-culture conversion and the frequency of adverse drug reactions related to cycloserine were assessed as well.ResultsAmong 325 MDR-TB patients, 144 were treated with cycloserine and 100 (69.4%) out of 144 successfully completed treatment. Compared with patients in non-cycloserine group, the hazard ratio of any unfavorable treatment outcome was 0.53 (95%CI: 0.35-0.81, P=0.003). Culture conversion rate at the intensive phase was similar whether cycloserine was administered or not (P=0.703). Of the 144 patients treated with cycloserine, a total of 16 (11.1%) patients experienced side-effects related to cycloserine, including 7 patients who discontinued cycloserine permanently.ConclusionsCycloserine could be an attractive agent to treat MDR-TB. Its safety profile warrants use in the most of MDR-TB cases. Cycloserine significantly improved the chance of favorable outcome for patients with simple MDR-TB but not pre-XDR-TB and XDR-TB. More aggressive regimens might be required for pre-XDR-TB or XDR-TB patients.

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