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. 2021 Apr 3;10(4):381.
doi: 10.3390/antibiotics10040381.

Repurposing Avermectins and Milbemycins against Mycobacteroides abscessus and Other Nontuberculous Mycobacteria

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Repurposing Avermectins and Milbemycins against Mycobacteroides abscessus and Other Nontuberculous Mycobacteria

Lara Muñoz-Muñoz et al. Antibiotics (Basel). .

Abstract

Infections caused by nontuberculous mycobacteria (NTM) are increasing worldwide, resulting in a new global health concern. NTM treatment is complex and requires combinations of several drugs for lengthy periods. In spite of this, NTM disease is often associated with poor treatment outcomes. The anti-parasitic family of macrocyclic lactones (ML) (divided in two subfamilies: avermectins and milbemycins) was previously described as having activity against mycobacteria, including Mycobacterium tuberculosis, Mycobacterium ulcerans, and Mycobacterium marinum, among others. Here, we aimed to characterize the in vitro anti-mycobacterial activity of ML against a wide range of NTM species, including Mycobacteroides abscessus. For this, Minimum Inhibitory Concentration (MIC) values of eight ML were determined against 80 strains belonging to nine different NTM species. Macrocyclic lactones showed variable ranges of anti-mycobacterial activity that were compound and species-dependent. Milbemycin oxime was the most active compound, displaying broad-spectrum activity with MIC lower than 8 mg/L. Time kill assays confirmed MIC data and showed bactericidal and sterilizing activity of some compounds. Macrocyclic lactones are available in many formulations and have been extensively used in veterinary and human medicine with suitable pharmacokinetics and safety properties. This information could be exploited to explore repurposing of anti-helminthics for NTM therapy.

Keywords: Mycobacteroides abscessus; avermectins; milbemycin oxime; nontuberculous mycobacteria; repurposing; selamectin.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
In vitro susceptibility of nontuberculosis mycobacteria (NTM) against different avermectins and milbemycins. (A) Heat map representation of the most common MIC values of eight ML against a panel of NTM strains. (B) MIC distribution of the most active ML against clinically relevant NTM strains. ABA, abamectin; DOR, doramectin; EMA, emamectin; EPR, eprinomectin; IVM, ivermectin; MBO, milbemycin oxime; MOX, moxidectin; SEL, selamectin.
Figure 2
Figure 2
In vitro Time Kill Assays of milbemycin oxime against different RGM and SGM species. Clarithromycin was also included as internal control of activity. Compounds were tested at 8 mg/L and 80 mg/L, i.e., 1×MIC and 10×MIC of milbemycin oxime, respectively. MBO, milbemycin oxime; CLA, clarithromycin.

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