Bedaquiline and Delamanid for Drug-Resistant Tuberculosis: A Clinician’s Perspective

Guglielmetti, Lorenzo; Chiesi, Sheila; Eimer, Johannes; Domínguez, José; Masini, Tiziana; Varaine, Francis; Véziris, Nicolas; Ader, Florence; Robert, Jérôme

doi:10.2217/fmb-2019-0309

Cited by 16 publications

(8 citation statements)

References 111 publications

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“…A number of challenges such as patient adherence, long duration of treatment and late diagnosis have also been linked to treatment failure in TB therapy [4]. Particularly, longer regimens involved in the treatment of DR-TB can potentially explain the higher non-adherence and treatment defaulting seen in these patients [5].…”

Section: Introductionmentioning

confidence: 99%

First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda

Kabahita¹,

Kabugo²,

Kakooza

et al. 2022

Antimicrob Resist Infect Control

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Background Uganda remains one of the countries with the highest burden of TB/HIV. Drug-resistant TB remains a substantial challenge to TB control globally and requires new strategic effective control approaches. Drug resistance usually develops due to inadequate management of TB patients including improper treatment regimens and failure to complete the treatment course which may be due to an unstable supply or a lack of access to treatment, as well as patient noncompliance. Methods Two sputa samples were collected from Xpert MTB/RIF® assay-diagnosed multi-drug resistant tuberculosis (MDR-TB) patient at Lira regional referral hospital in northern Uganda between 2020 and 2021 for comprehensive routine mycobacterial species identification and drug susceptibility testing using culture-based methods. Detection of drug resistance-conferring genes was subsequently performed using whole-genome sequencing with Illumina MiSeq platform at the TB Supranational Reference Laboratory in Uganda. Results In both isolates, extensively drug-resistant TB (XDR-TB) was identified including resistance to Isoniazid (katG p.Ser315Thr), Rifampicin (rpoB p.Ser450Leu), Moxifloxacin (gyrA p.Asp94Gly), Bedaquiline (Rv0678 Glu49fs), Clofazimine (Rv0678 Glu49fs), Linezolid (rplC Cys154Arg), and Ethionamide (ethA c.477del). Further analysis of these two high quality genomes revealed that this 32 years-old patient was infected with the Latin American Mediterranean TB strain (LAM). Conclusions This is the first identification of extensively drug-resistant Mycobacterium tuberculosis clinical isolates with bedaquiline, linezolid and clofazimine resistance from Uganda. These acquired resistances were because of non-adherence as seen in the patient’s clinical history. Our study also strongly highlights the importance of combating DR-TB in Africa through implementing next generation sequencing that can test resistance to all drugs while providing a faster turnaround time. This can facilitate timely clinical decisions in managing MDR-TB patients with non-adherence or lost to follow-up.

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Section: Introductionmentioning

confidence: 99%

First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda

Kabahita¹,

Kabugo²,

Kakooza

et al. 2022

Antimicrob Resist Infect Control

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“…Regarding the reasons for the development of acquired drug resistance to Bdq, the second clinical case, as examples of other authors, has demonstrated low adherence to treatment. Mallick J. S. et al [2], Liu Y. et al [3], Guglielmetti L. et al [4] indicate the reasons of this outcome: the prescription of Bdq to patients with initially low adherence to treatment, a high frequency of self-discontinuation of AMBT by patients.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, an important task of health care remains to search for ways of problem solving of improving effectiveness of DR-TB patient treatment. New regimens for the treatment of patients with multidrug-resistant tuberculosis (MDR-TB) have now been approved, including new anti-tuberculosis drugs, one of them is Bedaquiline (Bdq), which belongs to the antimycobacterial drugs from group A (the most highly effective drugs) [1,4,6,7,13,18]. Bdq-containing regimens of antimycobacterial therapy (AMBT) are associated with better outcomes and treatment safety [8,9,10,16,21,23].Mishra G. P, Mulani J.[15] identified a mutation in the Rv0678 gene associated with resistance to Bdq and UDC 616.…”

mentioning

confidence: 99%

Bedaquiline resistance in Mycobacterium tuberculosis during antimycobacterial therapy and its impact on clinical outcomes (clinical cases)

Raznatovska

Yasinskyi²,

Shalmin³

et al. 2023

ZMJ

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Aim. To analyze the nature of Bedaquiline (Bdq) resistance in Mycobacterium tuberculosis (MBT) during antimycobacterial therapy (AMBT) in patients with multidrug-resistant tuberculosis (MDR-TB), its impact on clinical outcomes and to detect risk factors for the Bdq drug resistance development on the example of own observed clinical cases. Materials and methods. 2 clinical cases of own observations of the Bdq resistance development in MBT during AMBT in patients with MDR-TB who were treated at the clinical base of the Department of Phthisiology and Pulmonology of Zaporizhzhia State Medical University – Pulmonary Tuberculosis Department No. 2 of the Communal Non-profit Organization “Zaporizhzhia Regional Phthisio-Pulmonology Clinical Treatment and Diagnostic Center” are presented. Results. The presented clinical cases confirm the literature data that the treatment effectiveness in patients with Rifampicin-resistant TB (RR-TB) and MDR-TB is associated with Bdq drug resistance. Regarding the reasons for the development of acquired Bdq drug resistance, the second clinical case, like the examples of other authors, demonstrates low adherence to treatment. There is no data in the literature about the lack of controlled treatment at the outpatient stage as a risk factor for Bdq drug resistance and negative clinical outcomes in patients with MDR-TB, which would complement the scientific experience in this problem. Conclusions. In both clinical cases, Bdq drug resistance was acquired (secondary), and had an impact on the clinical outcomes of tuberculosis treatment. The risk factors for Bdq drug resistance and negative clinical outcomes were lack of controlled treatment at the outpatient stage in the first case and low adherence to treatment in the second one.

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“…The study by Chesov et al adds up to an already rich body of observational evidence supporting the use of bedaquiline for MDR-TB [12]. Large, multinational cohort studies and a meta-analysis of individual patient data have confirmed the efficacy of this drug.…”

Section: Textmentioning

confidence: 99%

The coming-of-age of bedaquiline: a tale with an open ending

Guglielmetti

Varaine

2021

Eur Respir J

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Bedaquiline and Delamanid for Drug-Resistant Tuberculosis: A Clinician’s Perspective

Cited by 16 publications

References 111 publications

First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda

First report of whole-genome analysis of an extensively drug-resistant Mycobacterium tuberculosis clinical isolate with bedaquiline, linezolid and clofazimine resistance from Uganda

Bedaquiline resistance in Mycobacterium tuberculosis during antimycobacterial therapy and its impact on clinical outcomes (clinical cases)

The coming-of-age of bedaquiline: a tale with an open ending

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