In vitro activity of bedaquiline against Mycobacterium avium complex

Litvinov, Vitaly I.; Makarova, Marina; Kudlay, Dmitry; Nikolenko, N. Yu.; Mikhailova, Julia

doi:10.1099/jmm.0.001439

Cited by 6 publications

(6 citation statements)

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“…Two studies reported on MIC distribution of SGM species in 7H9. 36 , 49 In one study, the bedaquiline MIC distributions of M. avium and M. intracellulare in 7H9 were mostly in the ranges 0.003–1.0 and 0.003–0.5 mg/L, respectively, with the MIC modes being 0.015 and 0.007 mg/L, respectively (Figure S3 ). The majority of M. avium (98/124; 79.0%) and M. intracellulare (37/42; 88.1%) isolates had a bedaquiline MIC of <0.03 mg/L.…”

Section: Resultsmentioning

confidence: 99%

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Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis

Omar,

Whitfield,

Nolan

et al. 2023

Journal of Antimicrobial Chemotherapy

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Background Non-tuberculous mycobacteria (NTM) infections are increasing in incidence and associated mortality. NTM are naturally resistant to a variety of antibiotics, complicating treatment. We conducted a literature assessment on the efficacy of bedaquiline in treating NTM species in vitro and in vivo (animal models and humans); meta-analyses were performed where possible. Method Four databases were searched using specific terms. Publications were included according to predefined criteria. Bedaquiline’s impact on NTM in vitro, MICs and epidemiological cut-off (ECOFF) values were evaluated. A meta-analysis of bedaquiline efficacy against NTM infections in animal models was performed. Culture conversion, cure and/or relapse-free cure were used to evaluate the efficacy of bedaquiline in treating NTM infection in humans. Results Fifty studies met the inclusion criteria: 33 assessed bedaquiline’s impact on NTM in vitro, 9 in animal models and 8 in humans. Three studies assessed bedaquiline’s efficacy both in vitro and in vivo. Due to data paucity, an ECOFF value of 0.5 mg/mL was estimated for Mycobacterium abscessus only. Meta-analysis of animal studies showed a 1.86× reduction in bacterial load in bedaquiline-treated versus no treatment within 30 days. In humans, bedaquiline-including regimens were effective in treating NTM extrapulmonary infection but not pulmonary infection. Conclusions Bedaquiline demonstrated strong antibacterial activity against various NTM species and is a promising drug to treat NTM infections. However, data on the genomic mutations associated with bedaquiline resistance were scarce, preventing statistical analyses for most mutations and NTM species. Further studies are urgently needed to better inform treatment strategies.

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Section: Resultsmentioning

confidence: 99%

“…Using the proposed T-ECOFF value, only two isolates of M. avium and three isolates of M. intracellulare were found to be resistant to bedaquiline in 7H9. 36 …”

Section: Resultsmentioning

confidence: 99%

Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis

Omar,

Whitfield,

Nolan

et al. 2023

Journal of Antimicrobial Chemotherapy

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“…Bedaquiline, on the other hand, shows low in vitro inhibitory concentrations against MAC pathogens, comparable to those for M. tuberculosis [ 105 , 106 , 107 , 108 ], which gives hope that it will be effective. However, for a small number of cases, the bimodal distribution of bedaquiline MICs was recorded with an increase at high (2–8 mg/L) concentrations [ 109 , 110 ], which indicates the existence of intrinsically resistant strains.…”

Section: Discussionmentioning

confidence: 99%

Variability of Mycobacterium avium Complex Isolates Drug Susceptibility Testing by Broth Microdilution

Zimenkov

2022

Antibiotics

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Non-tuberculous mycobacteria are widely distributed in environments and are capable of infecting humans, particularly those with a compromised immune system. The most prevalent species that cause nontuberculous mycobacterial lung diseases are slow-growing bacteria from the Mycobacterium avium complex (MAC), mainly M. avium or M. intracellulare. The key treatment of MAC infections includes macrolides, ethambutol, and rifampicin; however, the therapy outcomes are unsatisfactory. Phenotypic drug susceptibility testing is a conditional recommendation prior to treatment, and critical concentrations for clarithromycin, amikacin, moxifloxacin, and linezolid have been established. In this review, data from studies on the determination of MIC of clinical isolates using the broth microdilution method were summarized. A significant variation in the MIC distributions from different studies was found. The main reasons could impact the findings: insufficient reproducibility of the phenotypic testing and variation in species lineages identified in different laboratories, which could have various intrinsic susceptibility to drugs. For most of the drugs analyzed, the MICs are too high, which could undermine the treatment efficiency. Further improvement of treatment outcomes demands the validation of microbiological resistance criteria together with the identification of molecular mechanisms of resistance.

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“…Прежде чем использовать Bdq для химио терапии микобактериозов, изучали ЛЧ к нему M. tuberculosis [18,19] и НТМБ, в том числе M. kansasii [3,17,[20][21][22][23][24][25][26]. Однако в литературных источниках недостаточно данных для полноценного понимания проблемы.…”

Section: Introductionunclassified

Drug Sensitivity to Bedaquiline of M. kansasii Strains Isolated in Antituberculous Institutions of the City of Moscow

Makarova,

Mikhajlova,

Khachaturiants

et al. 2023

Epidemiology and Vaccinal Prevention

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Relevance. M. kansasii are one of the main nontuberculous bacteria pathogens causing mycobacterial infections in most European countries (including Russia). An important problem in the treatment of mycobacteriosis is the resistance of their pathogens to antibacterial drugs (ABDs). Bedaquiline (Bdq) is one of the new ABDs, the effectiveness of which is shown, in particular, in the most common mycobacteriosis – tuberculosis.Aim. To characterize the features of drug sensitivity of M. kansasii isolated from respiratory material at the Moscow Scientific and Practical Center for Tuberculosis Control (MNPC BT).Materials and methods. A total of 76 M. kansasii cultures have been studied. The MIC spectrum of Bdq was determined for M. kansasii, MIC50, MIC90 (the concentrations of Bdq providing inhibition of the growth of 50% and 90% mycobacterial strains, respectively) and ECOFF (epidemiological cut-off value) – the MIC value characterizing the upper limit for the «wild» population type, which was determined using the ECOFFinder statistical calculator – EUCAST. The drug sensitivity of M. kansasii to the main ABDs used in general practice for the treatment of the corresponding mycobacterioses was also evaluated.Results. It was found that the MIC of Bdq in relation to M. kansasii were distributed in the range of 0.003-2.0 (mcg/ml), the growth of most strains (73.7%) was be inhibited by the concentration of Bdq0.015 mcg/ml. Among all studied strains of M. kansasii, the number of isolates resistant to Bdq were 2 (2.6%). The data obtained are generally consistent with the data of other authors and show that Bdq can currently be an effective drug for the treatment of mycobacterial infections caused by M. kansasii.Conclusion. The results of the study, as well as literature data, indicate that M. kansasii is currently usually sensitive to Bdq. However, in some cases, resistance to this drug is already developing.

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In vitro activity of bedaquiline against Mycobacterium avium complex

Cited by 6 publications

References 48 publications

Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis

Bedaquiline for treatment of non-tuberculous mycobacteria (NTM): a systematic review and meta-analysis

Variability of Mycobacterium avium Complex Isolates Drug Susceptibility Testing by Broth Microdilution

Drug Sensitivity to Bedaquiline of M. kansasii Strains Isolated in Antituberculous Institutions of the City of Moscow

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