Evolution of rifampicin treatment for tuberculosis

Grobbelaar, Melanie; Louw, Gail; Sampson, Samantha L.; Helden, Paul D. van; Donald, Peter R.; Warren, Robin M.

doi:10.1016/j.meegid.2019.103937

Cited by 81 publications

(58 citation statements)

References 84 publications

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“…Despite that, only 10 of those compounds are considered candidates for further development, presenting minimum inhibitory concentration (MIC) values below 64 µg/mL and a selectivity index (SI, CC 50 /MIC) higher than 10 [31]. Table 1 shows the activity of laurinterol and aplysin against nine M. tuberculosis strains, in comparison to that of rifampicin, the most common drug for TB treatment [32], used as positive control. Laurinterol inhibited eight out of the nine strains of Mtb, with MICs ≤ 100 µg/mL.…”

Section: Resultsmentioning

confidence: 99%

Antimycobacterial Activity of Laurinterol and Aplysin from Laurencia johnstonii

et al. 2020

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Marine environments represent a great opportunity for the discovery of compounds with a wide spectrum of bioactive properties. Due to their large variety and functions derived from natural selection, marine natural products may allow the identification of novel drugs based not only on newly discovered bioactive metabolites but also on already known compounds not yet thoroughly investigated. Since drug resistance has caused an increase in infections by Mycobacterium tuberculosis and nontuberculous mycobacteria, the re-evaluation of known bioactive metabolites has been suggested as a good approach to addressing this problem. In this sense, this study presents an evaluation of the in vitro effect of laurinterol and aplysin, two brominated sesquiterpenes isolated from Laurencia johnstonii, against nine M. tuberculosis strains and six nontuberculous mycobacteria (NTM). Laurinterol exhibited good antimycobacterial activity, especially against nontuberculous mycobacteria, being remarkable its effect against Mycobacterium abscessus, with minimum inhibitory concentration (MIC) values lower than those of the reference drug imipenem. This study provides further evidence for the antimycobacterial activity of some sesquiterpenes from L. johnstonii, which can be considered interesting lead compounds for the discovery of novel molecules to treat NTM infections.

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Section: Resultsmentioning

confidence: 99%

Antimycobacterial Activity of Laurinterol and Aplysin from Laurencia johnstonii

et al. 2020

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“…Compound 1 inhibited eight out of the nine strains of Mtb with MICs ≤ 100 μg/mL. M. tuberculosis CIPTIR-F296 was the most susceptible strain for both compounds; laurinterol was more active, showing MIC value of 25 µ g/mL, even lower than rifampicin (32 µ g/mL), the most used drug in TB treatment [32]. In comparison with TB treatments, the anti-NTM therapies have been remarkably neglected.…”

Section: Resultsmentioning

confidence: 99%

Antimycobacterial Activity of Laurinterol and Aplysin from <i>Laurencia johnstonii</i>

García-Davis¹,

Leal-López²,

Molina-Torres³

et al. 2020

Preprint

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Marine environments represent a great opportunity for the discovery of compounds with a wide spectrum of bioactive properties. Due to the privileged conditions of natural selection, marine natural products are subject to overcome the pressure put on identify novel drugs; not only in the case of newly discovered bioactive metabolites, but also in those previously known. Since drug resistance has caused an increase in infections caused by tuberculous and nontuberculous Mycobacteria, the re-evaluation of known bioactive metabolites has been suggested as a means to address this problem. In this sense, this study presents an evaluation of in vitro effect of laurinterol (1) and aplysin (2), two brominated sesquiterpenes isolated from Laurencia johnstonii against nine Mycobacterium tuberculosis strains and six nontuberculous mycobacteria. Laurinterol (1) exhibited good anti-tuberculous activity, especially against nontuberculous mycobacteria, being remarkable the effect against M. abscessus with MIC values lower than the reference drug imipenem. This study provides further evidence for the antimycobacterial activity of some sesquiterpenes from L. johnstonii, that can be considered an interesting lead compound for the discovery of novel antimycobacterial molecules to treat NTM infections.

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“…If FDCs are not used, it is also possible to suboptimally implement specific components of the regimen. During the continuation phase of treatment, suboptimal implementation of one drug will lead to monotherapy; the risk of drug resistance posed by monotherapy was illustrated by one of the first rifampicin trials in 1968 [77,78]. As a result, the current ethical maximum for monotherapy studies is 14 days [79].…”

Section: Suboptimal Implementation and Regimen Forgivenessmentioning

confidence: 99%

All nonadherence is equal but is some more equal than others? Tuberculosis in the digital era

et al. 2020

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Adherence to treatment for tuberculosis (TB) has been a concern for many decades, resulting in the World Health Organization's recommendation of the direct observation of treatment in the 1990s. Recent advances in digital adherence technologies (DATs) have renewed discussion on how to best address nonadherence, as well as offering important information on dose-by-dose adherence patterns and their variability between countries and settings. Previous studies have largely focussed on percentage thresholds to delineate sufficient adherence, but this is misleading and limited, given the complex and dynamic nature of adherence over the treatment course. Instead, we apply a standardised taxonomy – as adopted by the international adherence community – to dose-by-dose medication-taking data, which divides missed doses into 1) late/noninitiation (starting treatment later than expected/not starting), 2) discontinuation (ending treatment early), and 3) suboptimal implementation (intermittent missed doses). Using this taxonomy, we can consider the implications of different forms of nonadherence for intervention and regimen design. For example, can treatment regimens be adapted to increase the “forgiveness” of common patterns of suboptimal implementation to protect against treatment failure and the development of drug resistance? Is it reasonable to treat all missed doses of treatment as equally problematic and equally common when deploying DATs? Can DAT data be used to indicate the patients that need enhanced levels of support during their treatment course? Critically, we pinpoint key areas where knowledge regarding treatment adherence is sparse and impeding scientific progress.

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Evolution of rifampicin treatment for tuberculosis

Cited by 81 publications

References 84 publications

Antimycobacterial Activity of Laurinterol and Aplysin from Laurencia johnstonii

Antimycobacterial Activity of Laurinterol and Aplysin from Laurencia johnstonii

Antimycobacterial Activity of Laurinterol and Aplysin from <i>Laurencia johnstonii</i>

All nonadherence is equal but is some more equal than others? Tuberculosis in the digital era

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