Advances in the design of combination therapies for the treatment of tuberculosis

Larkins-Ford, Jonah; Aldridge, Bree B.

doi:10.1080/17460441.2023.2157811

Cited by 13 publications

(7 citation statements)

References 192 publications

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“…Using different drug combinations with the newly approved drugs including BDQ 1 , DLM 2 , PA-824 3 , and the standard first-line drugs, various clinical studies have been performed for drug-resistant TB treatment. These have led to better evaluation of the drugs with other drugs in combination. − BDQ 1 has proven to be a valuable treatment option, as it has demonstrated benefits such as a shorter period of sputum culture, strong bactericidal activity, and minimal adverse effects. Its clinical trial results have shown that BDQ 1 is now indispensable for the treatment of drug-resistant TB.…”

Section: Clinical Studies and Adverse Eventsmentioning

confidence: 99%

Unraveling Dilemmas and Lacunae in the Escalating Drug Resistance of Mycobacterium tuberculosis to Bedaquiline, Delamanid, and Pretomanid

Negi,

Perveen,

Gupta

et al. 2024

J. Med. Chem.

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Delamanid, bedaquiline, and pretomanid have been recently added in the anti-tuberculosis (anti-TB) treatment regimens and have emerged as potential solutions for combating drug-resistant TB. These drugs have proven to be effective in treating drug-resistant TB when used in combination. However, concerns have been raised about the eventual loss of these drugs due to evolving resistance mechanisms and certain adverse effects such as prolonged QT period, gastrointestinal problems, hepatotoxicity, and renal disorders. This Perspective emphasizes the properties of these first-in-class drugs, including their mechanism of action, pharmacokinetics/pharmacodynamics profiles, clinical studies, adverse events, and underlying resistance mechanisms. A brief coverage of efforts toward the generation of best-in-class leads in each class is also provided. The ongoing clinical trials of new combinations of these drugs are discussed, thus providing a better insight into the use of these drugs while designing an effective treatment regimen for resistant TB cases. ■ SIGNIFICANCE• The approval of delamanid, bedaquiline, and pretomanid constitutes a significant breakthrough in addressing drug-resistant tuberculosis. • Despite initial success, resistance mechanisms have emerged against these drugs. The current Perspective addresses this issue by shedding light on the specific mutations and mechanisms responsible for the resistance. • This Perspective assesses the current status of these firstin-class drugs and explores "best-in-class" drugs as potential leads to enhance efficacy and counter resistance.

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Section: Clinical Studies and Adverse Eventsmentioning

confidence: 99%

Unraveling Dilemmas and Lacunae in the Escalating Drug Resistance of Mycobacterium tuberculosis to Bedaquiline, Delamanid, and Pretomanid

Negi,

Perveen,

Gupta

et al. 2024

J. Med. Chem.

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“…Subsequently, combination therapy with isoniazid, ethambutol, and rifampicin was introduced as a drug combination therapy [ 23 ]. Treating MTB strains, both drug-susceptible and drug-resistant, requires a minimum of three to four antibiotics in combination, resulting in intricate drug susceptibility and resistance patterns [ 24 ].…”

Section: Combination Therapies Against Clinically Relevant Microorgan...mentioning

confidence: 99%

Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions

Morales-Durán,

León-Buitimea,

Morones-Ramírez

2024

Heliyon

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“…These compartments will be target sites for precisely selected and screened molecules. When combining in vitro conditions into one model, the researchers have to take into strong consideration the broth-based in vitro composition, changes in the pH value and oxygen levels during particular phases of the infection, or the availability of oxygen [ 132 , 133 ]. Hollow fiber systems allow for in vitro investigations into the pharmacodynamic/pharmacokinetic profile of a drug, or combination(s), and these evaluations are more consistent with in vivo pharmacokinetic studies [ 133 ].…”

Section: Several Innovations Within In Vitro Screening Approaches For...mentioning

confidence: 99%

Research in the Field of Drug Design and Development

Biala,

Kedzierska,

Kruk-Slomka

et al. 2023

Pharmaceuticals

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The processes used by academic and industrial scientists to discover new drugs have recently experienced a true renaissance, with many new and exciting techniques being developed over the past 5–10 years alone. Drug design and discovery, and the search for new safe and well-tolerated compounds, as well as the ineffectiveness of existing therapies, and society’s insufficient knowledge concerning the prophylactics and pharmacotherapy of the most common diseases today, comprise a serious challenge. This can influence not only the quality of human life, but also the health of whole societies, which became evident during the COVID-19 pandemic. In general, the process of drug development consists of three main stages: drug discovery, preclinical development using cell-based and animal models/tests, clinical trials on humans and, finally, forward moving toward the step of obtaining regulatory approval, in order to market the potential drug. In this review, we will attempt to outline the first three most important consecutive phases in drug design and development, based on the experience of three cooperating and complementary academic centers of the Visegrád group; i.e., Medical University of Lublin, Poland, Masaryk University of Brno, Czech Republic, and Comenius University Bratislava, Slovak Republic.

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Advances in the design of combination therapies for the treatment of tuberculosis

Cited by 13 publications

References 192 publications

Unraveling Dilemmas and Lacunae in the Escalating Drug Resistance of Mycobacterium tuberculosis to Bedaquiline, Delamanid, and Pretomanid

Unraveling Dilemmas and Lacunae in the Escalating Drug Resistance of Mycobacterium tuberculosis to Bedaquiline, Delamanid, and Pretomanid

Unraveling resistance mechanisms in combination therapy: A comprehensive review of recent advances and future directions

Research in the Field of Drug Design and Development

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