β-Lactams against Tuberculosis — New Trick for an Old Dog?

Diacon, Andreas H.; Merwe, Lize van der; Barnard, Marinus; Groote-Bidlingmaier, Florian von; Lange, Christoph; García‐Basteiro, Alberto L.; Sevene, Esperança; Ballell, Lluís; Barros-Aguirre, David

doi:10.1056/nejmc1513236

Cited by 114 publications

(121 citation statements)

References 4 publications

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“…However, a lack of an active oral formulation and the necessity of combining amoxicillin-clavulanate (to protect it from ß-lactamases) renders these compounds less appealing, even though some appear very active with excellent tolerability and safety. [80][81][82] Linezolid, an oxazolidinone, has demonstrated anti-mycobacterial efficacy and is included in many drug trial regimens; 83 however, its toxicity profile does not allow for its use beyond drug-resistant TB. Sutezolid and delpazolid are two newer generation oxazolidinones in early clinical trials which are hoped to be just as effective as linezolid but less toxic.…”

Section: Repurposed Drugsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

308

275

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Tuberculosis (TB) remains the top killer from an infectious globally causing an estimated 1.674.000 million deaths worldwide. In 2016, WHO estimates 600.000 cases of rifampicin-resistant TB of which 490.000 had multidrug-resistant (MDR) and less than half of them survive after receiving currently recommended WHO treatment regimens, illustrating weaknesses in current treatment approaches. We review progress and advances in the development of new and repurposed TB drugs, treatment trials and host-directed therapies. Updates are provided on phase 3 trials of the new compounds bedaquiline, delamanid, pretomanid; phase 2 trials of sutezolid, SQ-109, LCB01-0371, PBTZ-169; and five new drugs in phase 1 development. Approved or repurposed drugs undergoing further testing are rifampicin, rifapentine, clofazimine, and linezolid. Update on ongoing clinical trials, which aim to shorten TB treatment and improve treatment outcome is given. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR-TB, and five antimicrobial drug candidates are in phase 1 (Q203, TBI-166, OPC-167832, GSK 070, TBA-7371) and 5 in pre-clinical studies. Specific issues of safety and toxicity; drug-drug interactions; Therapeutic Drug Monitoring are reviewed. A wide range of candidate host-directed therapies (HDTs) and immune-based treatments are being investigated to accelerate the eradication of M.tb infection and for use as adjunctive therapy in shortening duration of treatment, preventing permanent lung injury and improving treatment outcomes of MDR-TB. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented. Ongoing clinical trials of HDTs for TB treatment, the current HDT development pipeline and translational research efforts for advancing further HDT options are presented.5

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Section: Repurposed Drugsmentioning

confidence: 99%

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tiberi

Plessis

Walzl

et al. 2018

The Lancet Infectious Diseases

308

275

View full text Add to dashboard Cite

show abstract

“…The potential usefulness of meropenem plus clavulanate or imipenem plus clavulanate has been highlighted, but it is expensive, requires long-term intravenous access, and insufficient clinical evidence of its usefulness or effectiveness exists. 287,288 Use of linezolid, bedaquiline, and delamanid…”

Section: Principles Of Formulating a Treatment Regimen For Mdr And Xdmentioning

confidence: 99%

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Dheda

Gumbo

Maartens

et al. 2017

The Lancet Respiratory Medicine

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521

474

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“…Important to note that recent evidence suggests this category of drugs might have, in view of its bactericidal activity, the role of a core drug (39).…”

Section: Which Drugs Might Be Upgradedmentioning

confidence: 99%

Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives

Rendón¹,

Tiberi

Scardigli

et al. 2016

J. Thorac. Dis.

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β-Lactams against Tuberculosis — New Trick for an Old Dog?

Cited by 114 publications

References 4 publications

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

Tuberculosis: progress and advances in development of new drugs, treatment regimens, and host-directed therapies

The epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant, extensively drug-resistant, and incurable tuberculosis

Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives

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