Activity of the old antimicrobial nitroxoline against Mycobacterium abscessus complex isolates

Abstract

The old antimicrobial nitroxoline is approved to treat urinary tract infection (UTI) and is currently rediscovered for treatment of drug resistant pathogens. Mycobacteria of the Mycobacterium abscessus complex (MYABS) are rapid-growing nontuberculous mycobacteria that are associated with difficult to treat infections of the lungs in patients with pulmonary disorders such as cystic fibrosis. In this study we assessed the in vitro activity of nitroxoline against molecularly characterized drug resistant MYABS isolates from clinical samples to address potential repurposing of nitroxoline in difficult to treat MYABS infection. The isolates originated from clinical samples collected between 2010 and 2019 at the University Hospital of Cologne, Germany (N=16; 10/16 M. abscessus spp. abscessus, 4/16 M. abscessus spp. massiliense, 2/16 M. abscessus spp. bolletii). Nitroxoline activity was compared to standard antimicrobials recommended for treatment of MYABS infection. For drug susceptibility testing of nitroxoline and comparators broth microdilution was performed based on current CLSI guidelines. Nitroxoline yielded a MIC90 of 4 mg/L (range 2-4 mg/L), which is two twofold dilutions below the current EUCAST susceptibility breakpoint of ≤ 16 mg/L (limited to uncomplicated UTI and E. Coli). Resistance to other antimicrobials was common in our cohort (16/16 isolates resistant to ciprofloxacin, imipenem and doxycycline; 12/16 isolates resistant to tobramycin; 9/16 isolates resistant to cefoxitin; 7/16 isolates resistant to clarithromycin; 2/16 isolates resistant to amikacin). Nitroxoline has a promising in vitro-activity against drug resistant MYABS isolates. Future studies should investigate this finding with macrophage and in vivo models.