Comparison of two-drug combinations, amikacin/tigecycline/imipenem and amikacin/tigecycline/clarithromycin against Mycobacteroides abscessus subsp. abscessus using the in vitro time-kill assay

Nontuberculous mycobacteria include 198 mycobacterial species. Among these, Mycobacteroides abscessus is a rapidly growing mycobacteria that causes lung and skin infections. M. abscessus lung infections are difficult to treat due to the high levels of resistance to several classes of antibiotics. The current treatment is based on combining at least two or three antibiotics. However, treatment outcomes remain very poor. The objective was to compare the in vitro activity of amikacin, tigecycline, imipenem, and clarithromycin, alone and in two different three-drug combinations (amikacin/tigecycline/imipenem and amikacin/tigecycline/clarithromycin) against seven M. abscessus subsp. abscessus clinical isolates using the time-kill assay. The two combinations showed greater activity than the antibiotics tested individually. Even though both combinations showed similar activity as well as no antagonistic activity, the combination including imipenem could not be an alternative treatment against M. abscessus subsp. abscessus lung infections caused by clarithromycin susceptible isolates. However, this combination could be considered against clarithromycin resistant isolates. Future studies are necessary to confirm this hypothesis This work was supported by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III, co-financed by the European Regional Development Fund (ERDF) ‘A way to achieve Europe’, the Spanish Ministry of Health (grant no. PI16/01047), Planes Nacionales de I+D+i 2008–2011/2013–2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI) (RD16/ 0016/0010) co‐financed by European Development Regional Fund (ERDF) “A way to achieve Europe” and operative program Intelligent Growth 2014–2020. This study was also supported by grant 2017SGR0809 from the Departament d’Universitats, Recerca i Societat de la Informació de la Generalitat de Catalunya and by a grant from Fundació La Marató de TV3 (grant no. 201816-10). EP-B received a grant from the Universitat de Barcelona (UB), Ajut de Personal Investigador en Formació (APIF-UB)