Activity of the old antimicrobial nitroxoline against Mycobacterium abscessus complex isolates

Ada Marie Hoffmann; Martina Wolke; Jan Rybniker; Georg Plum; Frieder Fuchs

doi:10.1016/j.jgar.2023.02.010

Activity of the old antimicrobial nitroxoline against Mycobacterium abscessus complex isolates

J Glob Antimicrob Resist. 2023 Jun:33:1-4. doi: 10.1016/j.jgar.2023.02.010. Epub 2023 Feb 24.

Authors

Ada Marie Hoffmann¹, Martina Wolke¹, Jan Rybniker², Georg Plum¹, Frieder Fuchs³

Affiliations

¹ Institute for Medical Microbiology, Immunology and Hygiene, Medical faculty and University Hospital of Cologne, Cologne, Germany.
² Department I of Internal Medicine, University of Cologne, Cologne, Germany; German Center for Infection Research (DZIF), partner site Bonn Cologne.
³ Institute for Medical Microbiology, Immunology and Hygiene, Medical faculty and University Hospital of Cologne, Cologne, Germany; Department of Microbiology and Hospital Hygiene, Bundeswehr Central Hospital Koblenz, Koblenz, Germany. Electronic address: frieder.fuchs@uk-koeln.de.

PMID: 36842457
DOI: 10.1016/j.jgar.2023.02.010

Abstract

Objectives: 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.

Methods: 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 Clinical and Laboratory Standards Institute (CLSI) guidelines.

Results: 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 Escherichia 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).

Conclusion: Nitroxoline has a promising in vitro activity against drug-resistant MYABS isolates. Future studies should investigate this finding with macrophage and in vivo models.

Keywords: Cystic fibrosis; Multidrug resistance; NTM; Quinoline; Tuberculosis; Xdr.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Infective Agents* / therapeutic use
Humans
Microbial Sensitivity Tests
Mycobacterium Infections, Nontuberculous* / drug therapy
Mycobacterium Infections, Nontuberculous* / microbiology
Mycobacterium abscessus*
Mycobacterium tuberculosis*

Substances

nitroxoline
Anti-Infective Agents