Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis

Nasiri, Mohammad Javad; Zangiabadian, Moein; Arabpour, Erfan; Amini, S.; Khalili, Farima; Centis, Rosella; D’Ambrosio, Lia; Denholm, Justin T.; Schaaf, H. Simon; Boom, Martin van den; Kurhasani, Xhevat; Dalcolmo, Margareth Pretti; Al-Abri, Seif; Chakaya, Jeremiah Muhwa; Alffenaar, Jan-Willem; Akkerman, Onno W.; Silva, Denise Rossato; Torrico, Marcela Muňoz; Seaworth, Barbara; Pontali, Emanuele; Saderi, Laura; Tiberi, Simon; Zumla, Alimuddin; Migliori, Giovanni Battista; Sotgiu, Giovanni

doi:10.1016/j.ijid.2022.02.043

Cited by 25 publications

(15 citation statements)

References 61 publications

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“…The nitroimidazoles, including delamanid and pretomanid, are antibacterial compounds that inhibit the synthesis of mycobacterial cell wall components [ 46 ]. Delamanid has been recommended by WHO for treatment of rifampicin-resistant/MDR-TB patients on longer regimens [ 1 ], with promising treatment outcome data for these regimens to date [ 47 ]. Pretomanid, developed by TB Alliance, features in the all-oral BPaL regimen, which was recently recommended by WHO for treatment of MDR-TB ( Figures 1 and 2 ) [ 2 ].…”

Section: Nitroimidazolesmentioning

confidence: 99%

Designing molecular diagnostics for current tuberculosis drug regimens

Georghiou

Vos

Velen

et al. 2023

Emerging Microbes & Infections

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Diagnostic development must occur in parallel with drug development to ensure the longevity of new treatment compounds. Despite an increasing number of novel and repurposed anti-tuberculosis compounds and regimens, there remains a large number of drugs for which no rapid and accurate molecular diagnostic option exists. The lack of rapid drug susceptibility testing for linezolid, bedaquiline, clofazimine, the nitroimidazoles (i.e pretomanid and delamanid) and pyrazinamide at any level of the healthcare system compromises the effectiveness of current tuberculosis and drug-resistant tuberculosis treatment regimens. In the context of current WHO tuberculosis treatment guidelines as well as promising new regimens, we identify the key diagnostic gaps for initial and follow-on tests to diagnose emerging drug resistance and aid in regimen selection. Additionally, we comment on potential gene targets for inclusion in rapid molecular drug susceptibility assays and sequencing assays for novel and repurposed drug compounds currently prioritized in current regimens, and evaluate the feasibility of mutation detection given the design of existing technologies. Based on current knowledge, we also propose design priorities for next generation molecular assays to support triage of tuberculosis patients to appropriate and effective treatment regimens. We encourage assay developers to prioritize development of these key molecular assays and support the continued evolution, uptake, and utility of sequencing to build knowledge of tuberculosis resistance mechanisms and further inform rapid treatment decisions in order to curb resistance to critical drugs in current regimens and achieve End TB targets. Trial registration: .

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Section: Nitroimidazolesmentioning

confidence: 99%

Designing molecular diagnostics for current tuberculosis drug regimens

Georghiou

Vos

Velen

et al. 2023

Emerging Microbes & Infections

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“…Подальша лікарська стійкість і непереносимість протитуберкульозних препаратів можуть обмежувати ефективність схем лікування в поєднанні з попередніми невдачами лікування, залежностями, алкоголізмом, коінфекцією ВІЛ і супутніми захворюваннями, що робить клінічне ведення особливо складним. Випадки лікарсько-стійкого ТБ потребують більше часу та ресурсів для тривалішого лікування й подальшого спостереження, хірургічне втручання не є рідкістю [3].…”

Section: вступunclassified

Treatment of MDR-TB/HIV/CMV patients under individualized regimes of antimycobacterial therapy

Lytvynenko¹,

Pohrebna²,

Senko³

et al. 2022

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BACKGROUND. Often in practice there are combinations of several diseases, or tuberculosis of the respiratory organs develops against the background of various comorbidities, including HIV. OBJECTIVE. To demonstrate best clinical practices for selecting the optimal individualized treatment regimen (ITR) in a patient with multidrug-resistant tuberculosis (MDR-TB) associated with HIV in the setting of severe immunosuppression and complicated by poor tolerability. MATERIALS AND METHODS. Presented clinical analysis of newly diagnosed generalized MDR-TB associated with HIV, treated for ITR for 9 months, which was assigned according to the World Health Organization step-by-step algorithm based on phenotypic drug susceptibility testing data. At the time of assessment, the patient was taking 273 doses of ITR. ITR required extended monitoring and selection during its first months of treatment, as it was accompanied by severe intolerance to antimycobacterial drugs. RESULTS AND DISCUSSION. The expressed adverse events of 3-4 degrees were managed at the expense of carrying out the strengthened clinical and laboratory monitoring and consultations of narrow experts that allowed to select optimum ITR and in addition to carry out symptomatic treatment. Such tactics led to the normalization of hematological parameters with the disappearance of clinical manifestations of other adverse events and provided high intermediate results of treatment at the 9th month of ITR. Steady negativity of smear and culture (from1st month of treatment), positive radiological dynamics and significant improvement of well-being were obtained. CONCLUSIONS. Management of patients with MDR-TB/HIV co-infection with severe immunosuppression in patients who are treated by ITR requires enhanced monitoring of adverse reactions and rapid changes in the composition of ITR and early symptomatic treatment to ensure better adherence to treatment and positive outcomes.

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“…Nowadays, the treatment of TB mainly depends on the conventional multidrug combination therapy . Over the past 50 years, there were only four new drugs, bedaquiline, delamanid, pretomanid, and linezonid, approved for the treatment of drug-resistant TB. Currently, only SQ109, an inhibitor of membrane transporter protein MmpL3, is being evaluated in phase III, while other candidates are distributed in early clinical stages.…”

Section: Introductionmentioning

confidence: 99%

Structure–Activity Relationship of Novel Pyrimidine Derivatives with Potent Inhibitory Activities against Mycobacterium tuberculosis

Tian

Huang

et al. 2023

J. Med. Chem.

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Discovery of novel antitubercular drugs is an effective strategy against drug-resistant tuberculosis (TB). Our previous study has identified LPX-16j as a novel antitubercular compound. Herein, we perform a comprehensive structure−activity relationship (SAR) based on LPX-16j, indicating that the central pyrimidine ring moiety was crucial for the antitubercular activities of its derivatives, and replacing the naphthyl group with hydrophobic substitutes was well tolerated. The representative derivative 5a exhibited potent activity against H37Ra, H37Rv, and clinical drug-resistant TB with minimum inhibitory concentration (MIC) values of 0.5−1.0 μg/mL. Meanwhile, 5a showed an acceptable safety in vivo and displayed a favorable oral bioavailability with a value of 40.7%. The differential scanning fluorescence, isothermal titration calorimetry, and molecular docking assays indicated that PknB could be one of the targets of compound 5a. Overall, this study identified 5a as a novel promising lead compound with the potential to develop candidates for the treatment of drug-resistant TB.

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Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis

Cited by 25 publications

References 61 publications

Designing molecular diagnostics for current tuberculosis drug regimens

Designing molecular diagnostics for current tuberculosis drug regimens

Treatment of MDR-TB/HIV/CMV patients under individualized regimes of antimycobacterial therapy

Structure–Activity Relationship of Novel Pyrimidine Derivatives with Potent Inhibitory Activities against Mycobacterium tuberculosis

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