AUTHOR=Aziz Dinah B. , Teo Jeanette W. P. , Dartois Véronique , Dick Thomas 

TITLE=Teicoplanin – Tigecycline Combination Shows Synergy Against Mycobacterium abscessus

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.00932

DOI=10.3389/fmicb.2018.00932

ISSN=1664-302X

ABSTRACT=<p>Lung disease caused by non-tuberculous mycobacteria (NTM), relatives of <italic>Mycobacterium tuberculosis</italic>, is increasing. <italic>M. abscessus</italic> is the most prevalent rapid growing NTM. This environmental pathogen is intrinsically resistant to most commonly used antibiotics, including anti-tuberculosis drugs. Current therapies take years to achieve cure, if cure if achieved. Thus, there is an urgent medical need to identify new, more efficacious treatments. Here, we explore the possibility of repurposing antibiotics developed for other indications. We asked whether novel two-drug combinations of clinically used antibiotics can be identified that show synergistic activity against this mycobacterium. An <italic>in vitro</italic> checkerboard titration assay was employed to test 180 dual combinations of 41 drugs against the clinical isolate <italic>M. abscessus</italic> Bamboo. The most attractive novel combination was further profiled against reference strains representing three sub-species (<italic>M. abscessus</italic> subsp. <italic>abscessus</italic>, <italic>massiliense</italic> and <italic>bolletii</italic>) and a collection of clinical isolates. This resulted in the identification of a novel synergistic antibiotic pair active against the <italic>M. abscessus</italic> complex: the glycopeptide teicoplanin with the glycylcycline tigecycline showed inhibitory activity at 2–3 μM (teicoplanin) and 1–2 μM (tigecycline). This novel combination can now be tested in <italic>M. abscessus</italic> animal models of infection and/or patients.</p>