Multidrug-resistant tuberculosis

Dheda, Keertan; Mirzayev, Fuad; Cirillo, Daniela Maria; Udwadia, Zarir; Dooley, Kelly E.; Chang, Kwok-Chiu; Omar, Shaheed Vally; Reuter, Anja; Perumal, Tahlia; Horsburgh, C. Robert; Murray, Megan; Lange, Christoph

doi:10.1038/s41572-024-00504-2

Cited by 34 publications

(1 citation statement)

References 191 publications

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“…The treatment of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) remains a global challenge due to the limited number of effective and tolerable drugs [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon?

Chen,

Burke,

Cho

et al. 2024

Pharmaceutics

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Multidrug-resistant tuberculosis (MDR-TB) is a global health concern. Standard treatment involves the use of linezolid, a repurposed oxazolidinone. It is associated with severe adverse effects, including myelosuppression and mitochondrial toxicity. As such, it is imperative to identify novel alternatives that are better tolerated but equally or more effective. Therefore, this review aims to identify and explore the novel alternative oxazolidinones to potentially replace linezolid in the management of TB. The keywords tuberculosis and oxazolidinones were searched in PubMed to identify eligible compounds. The individual drug compounds were then searched with the term tuberculosis to identify the relevant in vitro, in vivo and clinical studies. The search identified sutezolid, tedizolid, delpazolid, eperezolid, radezolid, contezolid, posizolid and TBI-223, in addition to linezolid. An additional search resulted in 32 preclinical and 21 clinical studies. All novel oxazolidinones except posizolid and eperezolid resulted in positive preclinical outcomes. Sutezolid and delpazolid completed early phase 2 clinical studies with better safety and equal or superior efficacy. Linezolid is expected to continue as the mainstay therapy, with renewed interest in drug monitoring. Sutezolid, tedizolid, delpazolid and TBI-223 displayed promising preliminary results. Further clinical studies would be required to assess the safety profiles and optimize the dosing regimens.

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Section: Introductionmentioning

confidence: 99%

New Oxazolidinones for Tuberculosis: Are Novel Treatments on the Horizon?

Chen,

Burke,

Cho

et al. 2024

Pharmaceutics

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Readability of Patient-Facing Information of Antibiotics Used in the WHO Short 6-Month and 9-Month All Oral Treatment for Drug-Resistant Tuberculosis

Moore,

Millar

2024

Lung

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Objectives Readability of patient-facing information of oral antibiotics detailed in the WHO all oral short (6 months, 9 months) has not been described to date. The aim of this study was therefore to examine (i) how readable patient-facing TB antibiotic information is compared to readability reference standards and (ii) if there are differences in readability between high-incidence countries versus low-incidence countries. Methods Ten antibiotics, including bedaquiline, clofazimine, ethambutol, ethionamide, isoniazid, levofloxacin, linezolid, moxifloxacin, pretomanid, pyrazinamide, were investigated. TB antibiotic information sources were examined, consisting of 85 Patient Information Leaflets (PILs) and 40 antibiotic web resouces. Of these 85 PILs, 72 were taken from the National Medicines Regulator from six countries (3 TB high-incidence [Rwanda, Malaysia, South Africa] + 3 TB low-incidence [UK, Ireland, Malta] countries). Readability data was grouped into three categories, including (i) high TB-incidence countries (n = 33 information sources), (ii) low TB-incidence countries (n = 39 information sources) and (iii) web information (n = 53). Readability was calculated using Readable software, to obtain four readability scores [(i) Flesch Reading Ease (FRE), (ii) Flesch-Kincaid Grade Level (FKGL), (iii) Gunning Fog Index and (iv) SMOG Index], as well as two text metrics [words/sentence, syllables/word]. Results Mean readability scores of patient-facing TB antibiotic information for FRE and FKGL, were 47.4 ± 12.6 (sd) (target ≥ 60) and 9.2 ± 2.0 (target ≤ 8.0), respectively. There was no significant difference in readability between low incidence countries and web resources, but there was significantly poorer readability associated with PILs from high incidence countries versus low incidence countries (FRE; p = 0.0056: FKGL; p = 0.0095). Conclusions Readability of TB antibiotic PILs is poor. Improving readability of PILs should be an important objective when preparing patient-facing written materials, thereby improving patient health/treatment literacy.

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