The challenge of the new tuberculosis drugs

Tiberi, Simon; Buchanan, Ruaridh; Caminero, José A.; Centis, Rosella; Arbex, Marcos Abdo; Salazar, Michelle C.; Potter, Jessica; Migliori, Giovanni Battista

doi:10.1016/j.lpm.2017.01.016

Cited by 44 publications

(31 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1 3 11 However, treatment success could be compromised by poor adherence mainly due to the long treatment period and the development of drug-resistant TB ultimately from the inadequate treatment of active TB. 9 11 In Ethiopia, this four-drug, 6-month and 9–12-month regimen is also recommended as a first-line drug for the treatment of active drug-susceptible pulmonary TB and extrapulmonary TB (EPTB), respectively. 12…”

Section: Introductionmentioning

confidence: 99%

Drug-susceptible tuberculosis treatment success and associated factors in Ethiopia from 2005 to 2017: a systematic review and meta-analysis

et al. 2018

View full text Add to dashboard Cite

ObjectivesThe main aim of this study was to assess the overall tuberculosis (TB) treatment success in Ethiopia and to identify potential factors for poor TB treatment outcome.DesignA systematic review and meta-analysis of published literature was conducted. Original studies were identified through a computerised systematic search using PubMed, Google Scholar and Science Direct databases. Heterogeneity across studies was assessed using Cochran’s Q test and I2 statistic. Pooled estimates of treatment success were computed using the random-effects model with 95% CI using Stata V.14 software.ResultsA total of 230 articles were identified in the systematic search. Of these 34 observational studies were eligible for systematic review and meta-analysis. It was found that 117 750 patients reported treatment outcomes. Treatment outcomes were assessed by World Health Organization (WHO) standard definitions of TB treatment outcome. The overall pooled TB treatment success rate in Ethiopia was 86% (with 95% CI 83%_88%). TB treatment success rate for each region showed that, Addis Ababa (93%), Oromia (84%), Amhara (86%), Southern Nations (83%), Tigray (85%) and Afar (86%). Mainly old age, HIV co-infection, retreatment cases and rural residence were the most frequently identified factors associated with poor TB treatment outcome.ConclusionThe result of this study revealed that the overall TB treatment success rate in Ethiopia was below the threshold suggested by WHO (90%). There was also a discrepancy in TB treatment success rate among different regions of Ethiopia. In addition to these, HIV co-infection, older age, retreatment cases and rural residence were associated with poor treatment outcome. In order to further improve the treatment success rate, it is strategic to give special consideration for regions which had low TB treatment success and patients with TB with HIV co-infection, older age, rural residence and retreatment cases.

show abstract

Section: Introductionmentioning

confidence: 99%

Drug-susceptible tuberculosis treatment success and associated factors in Ethiopia from 2005 to 2017: a systematic review and meta-analysis

et al. 2018

View full text Add to dashboard Cite

show abstract

“…In such cases, developing novel drugs or drug regimens is urgent and necessary for effective control of TB. Although significant progress has been made in identification of several new anti-TB compounds, such as bedaquiline, delamanid, and pretomanid, which are in phase II or III trials [ 5 , 6 ], long duration and high expenses lead to slow development of new drugs. Repurposing the currently used antibiotics may contribute to the development of novel anti-TB regimens.…”

Section: Introductionmentioning

confidence: 99%

In Vitro Activity of β-Lactams in Combination with β-Lactamase Inhibitors against Mycobacterium tuberculosis Clinical Isolates

Wan

Xiao

et al. 2018

BioMed Research International

View full text Add to dashboard Cite

Objectives Evaluating the activity of nineteen β-lactams in combination with different β-lactamase inhibitors to determine the most potent combination against Mycobacterium tuberculosis (MTB) in vitro. Methods Drug activity was examined by drug susceptibility test with 122 clinical isolates from China. Mutations of blaC and drug targets ldtMt1, ldtMt2, dacB2, and crfA were analyzed by nucleotide sequencing. Results Tebipenem (TBM) in combination with clavulanate (CLA) exhibited the highest anti-TB activity. The MIC of β-lactam antibiotics was reduced most evidently in the presence of CLA, compared to avibactam (AVI) and sulbactam (SUB). Eight polymorphism sites were identified in blaC, which were not associated with β-lactams resistance. Interestingly, one strain carrying G514A mutation in blaC was highly susceptible to β-lactams regardless of the presence of inhibitors. The transpeptidase encoding genes, ldtMt1, ldtMt2, and dacB2, harboured three mutations, two mutations, and one mutation, respectively, but no correlation was found between these mutations and drug resistance. Conclusion The activity of β-lactams against MTB and different synergetic effect of β-lactamase inhibitors were indicated. TBM/CLA exhibited the most activity and has a great prospect in developing novel anti-TB regimen; however, further clinical research is warranted. Moreover, the resistance to the β-lactam antibiotics might not be conferred by single target mutation in MTB and requires further studies.

show abstract

“…As problems such as DR-TB, MDR-TB, extensively drug-resistant TB (XDR-TB), and a recently emerging threat by a totally drug-resistant TB (TDR-TB) are increasing in prevalence, several novel drugs will cause a significant shift in the landscape of TB treatment but can cause some other ADEs/ADRs. For example, bedaquiline and delamanid can prolong cardiac QTc 12 13. The majority of TB patients receive community-based or home-based treatment; however, most studies of ADRs are hospital-based 9–11.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, it is necessary to study ADRs in other types of patients. In addition to first-line drugs, the number of second-line drugs and new drugs for treating different types of DR-TB patients are also gradually increasing,12 and ADRs induced by those drugs still need further study. Thus far, there are no other similar new cohorts in China that can satisfy the need for a study of ADEs/ADRs.…”

Section: Introductionmentioning

confidence: 99%

Home-based Anti-Tuberculosis Treatment Adverse Reactions (HATTAR) study: a protocol for a prospective observational study

Yang

Pan

et al. 2019

BMJ Open

View full text Add to dashboard Cite

IntroductionTuberculosis (TB) continues to be an important public health problem throughout much of the world. Drug treatment is the only effective treatment method, but adverse drug events (ADEs) and adverse drug reactions (ADRs) can affect medication adherence. As the number of drug-resistant TB patients and the number of anti-TB drugs have increased, it is necessary to explore the risk factors for ADEs/ADRs to reduce their occurrence. This study aims to build a home-based anti-TB treatment cohort and to recognise the incidences, prognosis and risk factors of anti-TB drug-induced ADEs/ADRs in real-world experiences.Methods and analysisThis study is a multicentre, prospective observational cohort study. The study population will consist of 3200 newly diagnosed TB patients between January 2019 and December 2020. After initiating the anti-TB treatment, all patients will be followed up until finishing treatment unless they withdraw, and we will record personal drug use and signs and/or symptoms of discomfort. Patients will receive scheduled laboratory tests in designated hospitals every 2 weeks during the first 2 months, and the residual blood sample after conducting the laboratory tests will be preserved. The ADEs/ADRs will be placed into eight categories: liver dysfunction, gastrointestinal reactions, drug allergy, arthralgia or muscle pain, nervous system disorders, haematological system disorders, renal impairment and others.Ethics and disseminationThis study protocol has been approved by the ethics committees of Nanjing Medical University. All patients will give written informed consent before enrollment. The findings of the study will be published in peer-reviewed journals and will be presented at national and international conferences.

show abstract

The challenge of the new tuberculosis drugs

Cited by 44 publications

References 71 publications

Drug-susceptible tuberculosis treatment success and associated factors in Ethiopia from 2005 to 2017: a systematic review and meta-analysis

Drug-susceptible tuberculosis treatment success and associated factors in Ethiopia from 2005 to 2017: a systematic review and meta-analysis

In Vitro Activity of β-Lactams in Combination with β-Lactamase Inhibitors against Mycobacterium tuberculosis Clinical Isolates

Home-based Anti-Tuberculosis Treatment Adverse Reactions (HATTAR) study: a protocol for a prospective observational study

Contact Info

Product

Resources

About