Activity of Rifabutin and Hemi-synthetic Derivatives Against Mycobacterium abscessus

Ramis, Ivy Bastos; Figueiredo, Ricardo G.; Ramos, Daniela Fernandes; Halicki, Priscila Cristina Bartolomeu; Groll, Andréa von; Viveiros, Miguel; Costa, María do Céu; Silva, Pedro E. A. da

doi:10.2174/1573406414666171204102633

Cited by 5 publications

(4 citation statements)

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“…Rifampicins have broad antimicrobial coverage and are frequently used in the treatment of NTM infections (Ramis et al 2018), presenting an additive interaction with the ethanolic extract of green propolis for M. chelonae and M. avium, similar to the findings reported by (Scheller et al 1999), which showed a positive interaction between the association of this antimicrobial with the ethanol extract of propolis against other mycobacteria.…”

Section: Resultssupporting

confidence: 82%

Green propolis as an adjuvant against nontuberculous mycobacteria

et al. 2021

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Natural products have been touted as important tools because of their vast potential for the development of compounds with antimicrobial activity and the possible inhibitory activity and/or adjuvant resistance mechanisms. Propolis has been empirically used for many years for the treatment of diseases, mainly due to its antioxidant, anti inflammatory and antimicrobial activities. This study aimed to evaluate the in vitro antimycobacterial activity of the ethanol extract of propolis alone and in combination with rifampicin (RIF), amikacin (AMI) and ciprofloxacin (CIP). The ethanol extract of propolis showed antibacterial activity against Mycobacterium chelonae and M. kansasii and was capable of increasing AMI, RIF and CIP activity in combination. On the other hand, compared to M. absecessus, M. fortuitum and M. avium, the extract was not active at 200 µg/mL and did not show pronounced adjuvant capacity when evaluated in association with the drugs. Based on these results, it can be concluded that the ethanol extract of propolis could be an alternative in the development of new drugs and can be used complementary with the current mycobacteriosis treatment.

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Section: Resultssupporting

confidence: 82%

Green propolis as an adjuvant against nontuberculous mycobacteria

et al. 2021

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“…The rifamycin rifabutin, has been recently shown to have in vitro activity against reference strains as well as clinical isolates of M. abscessus. This antimicrobial activity was approximately 10-fold greater than the activity rifampin and rifapentine, and was evident in clarithromycin- resistant strains (20,21). Unfortunately no pre-clinical in vivo or clinical data is available on its use in M. abscessus infection.…”

Section: Rifabutinmentioning

confidence: 98%

Experimental therapies of Mycobacterium abscessus infections

Meir¹,

Barkan²

2020

Preprint

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Mycobacterium abscessus is a non-tuberculous mycobacteria notoriously known for causing severe, chronic infections. Treatment of these infections is challenging due to either intrinsic or acquired resistance of M. abscessus to multiple antibiotics. Despite prolonged poly-antimicrobial therapy, treatment of M. abscessus infections often fails, leading to progressive morbidity and eventual mortality. Great research efforts are invested in finding new therapeutic options for M. abscessus. Clofazimine and rifabutin are known anti-mycobacterial antibiotics, repurposed for use against M. abscessus. Novel antimicrobials active against M. abscessus include delamanid, pretomanid and PIPD1 and the recently approved beta-lactamase inhibitors avibactam, relebactam and vaborbactam. Previously unused antimicrobial combinations e.g. vancomycin-clarithromycin and dual beta-lactam therapy have been shown to have synergistic effect against M. abscessus in experimental models, suggesting their possible use in multiple-drug regimens. Finally, engineered phage therapy has been reported to be clinically successful in a severe case of disseminated M. abscessus infection. While many of these experimental therapeutics have shown activity against M. abscessus in vitro, as well as intracellular and/or animal models, most have little if any evidence of effect in humans infections. Clinical studies of M. abscesssus treatments are needed in order to reliably determine the value of their incorporation in therapeutic regimens.

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“…We measured the growth inhibition activity of TBAJ-876 combined with clarithromycin, amikacin, cefoxitin or imipenem against M. abscessus Bamboo, using the 'checkerboard titration' assay. TBAJ-876 was also combined with rifabutin, recently shown to be active against M. abscessus and a potential repurposing candidate (52,(55)(56)(57)(58).…”

Section: Tbaj-876 Does Not Antagonize the Activity Of Commonly Used Anti-m Abscessusmentioning

confidence: 99%

TBAJ-876, a 3,5-Dialkoxypyridine Analogue of Bedaquiline, Is Active against Mycobacterium abscessus

Sarathy

Ganapathy

Zimmerman

et al. 2020

Antimicrob Agents Chemother

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Lung disease caused by Mycobacterium abscessus is very difficult to cure, and treatment failure rates are high. The antituberculosis drug bedaquiline (BDQ) is used as salvage therapy against this dreadful disease. However, BDQ is highly lipophilic, displays a long terminal half-life, and presents a cardiotoxicity liability associated with QT interval prolongation. Recent medicinal chemistry campaigns resulted in the discovery of 3,5-dialkoxypyridine analogues of BDQ which are less lipophilic, have higher clearance, and display lower cardiotoxic potential. TBAJ-876, a clinical development candidate of this series, shows attractive in vitro antitubercular activity and efficacy in a murine tuberculosis model. Here, we asked whether TBAJ-876 is active against M. abscessus. TBAJ-876 displayed submicromolar in vitro activity against reference strains representing the three subspecies of M. abscessus and against a collection of clinical isolates. Drug-drug potency interaction studies with commonly used anti-M. abscessus antibiotics showed no antagonistic effects, suggesting that TBAJ-876 could be coadministered with currently used drugs. Efficacy studies, employing a mouse model of M. abscessus infection, demonstrated potent activity in vivo. In summary, we demonstrate that TBAJ-876 shows attractive in vitro and in vivo activities against M. abscessus, similar to its BDQ parent. This suggests that next-generation BDQ, with improved tolerability and pharmacological profiles, may be useful for the treatment of M. abscessus lung disease in addition to the treatment of tuberculosis.

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Activity of Rifabutin and Hemi-synthetic Derivatives Against Mycobacterium abscessus

Abstract: Besides RFB 1, its derivatives 4, 10 and 11 show potential for clinical development in the M. abscessus treatment.

Cited by 5 publications

References 0 publications

Green propolis as an adjuvant against nontuberculous mycobacteria

Green propolis as an adjuvant against nontuberculous mycobacteria

Experimental therapies of Mycobacterium abscessus infections

TBAJ-876, a 3,5-Dialkoxypyridine Analogue of Bedaquiline, Is Active against Mycobacterium abscessus

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