Experiences of introducing new drugs for drug-resistant TB at the ALERT Hospital, Addis Ababa, Ethiopia, 2017–2019

Tesema, Emawayish; Wares, Fraser; Bedru, Ahmed; Negeri, C.; Molla, Yohannes; Gemechu, Diriba Sufa; Kassa, Andargachew; Tsegaye, F.; Taye, L.

doi:10.5588/pha.20.0065

Cited by 3 publications

(1 citation statement)

References 6 publications

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“…Multiple studies evaluated the adverse effects of DLM 2 . ,− The most common adverse effect observed during DLM 2 treatment is an increase in QTcF prolongation, which occurs due to cardiac repolarization caused by DLM 2 or its metabolites . The co-administration of DLM 2 with clofazimine has been discouraged due to concerns like cardiac arrhythmias, which may affect certain second-line MDR-TB drugs .…”

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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Mechanism of Action, Resistance, Synergism, and Clinical Implications of Delamanid Against Multidrug-Resistant Mycobacterium tuberculosis

et al. 2021

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Multidrug-resistant (MDR) isolates of Mycobacterium tuberculosis (MTB) remain a primary global threat to the end of tuberculosis (TB) era. Delamanid (DLM) is a nitro-dihydro-imidazooxazole derivative utilized to treat MDR-TB. DLM has distinct mechanism of action, inhibiting methoxy- and keto-mycolic acid (MA) synthesis through the F420 coenzyme mycobacteria system and generating nitrous oxide. While DLM resistance among MTB strains is uncommon, there are increasing reports in Asia and Europe, and such resistance will prolong the treatment courses of patients infected with MDR-TB. In this review, we address the antimycobacterial properties of DLM, report the global prevalence of DLM resistance, discuss the synergism of DLM with other anti-TB drugs, and evaluate the documented clinical trials to provide new insights into the clinical use of this antibiotic.

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Delamanid: Safety and Efficacy Analysis

Mozhokina,

Samoylova,

Vasilyeva

et al. 2023

Tuberk. bolezni lëgk.

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The review presents the analysis of 50 publications describing treatment of multiple drug resistant tuberculosis with regimens containing the new drug of delamanid. Delamanid possesses a dual bactericidal effect not only against active but also dormant Mycobacterium tuberculosis. The results of clinical studies on the efficacy and safety of delamanid within comprehensive chemotherapy are presented. The review demonstrates prospects for expanding the use of delamanid for treatment of adults and children.

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Experiences of introducing new drugs for drug-resistant TB at the ALERT Hospital, Addis Ababa, Ethiopia, 2017–2019

Cited by 3 publications

References 6 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

Mechanism of Action, Resistance, Synergism, and Clinical Implications of Delamanid Against Multidrug-Resistant Mycobacterium tuberculosis

Delamanid: Safety and Efficacy Analysis

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