Universität zu Köln

Hoffmann, Ada Marie, Wolke, Martina, Rybniker, Jan, Plum, Georg and Fuchs, Frieder ORCID: 0000-0001-7075-5378 (2022). In vitro Activity of Repurposed Nitroxoline Against Clinically Isolated Mycobacteria Including Multidrug-Resistant Mycobacterium tuberculosis. Front. Pharmacol., 13. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1663-9812

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Abstract

Antimicrobial treatment options for mycobacterial infections are limited due to intrinsic resistance and the emergence of acquired resistance in Mycobacterium tuberculosis. Isolates resisting first- and second line drugs are raising concerns about untreatable infections and make the development of new therapeutic strategies more pressing. Nitroxoline is an old oral antimicrobial that is currently repurposed for the treatment of urinary tract infection (UTI). In this study, we report the in vitro activity of nitroxoline against 18 clinical isolates of M. tuberculosis complex (MTBC) (M. tuberculosis N = 16, M. bovis BCG N = 1, M. bovis sp. bovis N = 1). Since nitroxoline achieves high concentrations in the urinary tract, we included all MTBC-isolates from urinary samples sent to our laboratory between 2008 and 2021 (University Hospital of Cologne, Germany). Isolates from other sources (N = 7/18) were added for higher sample size and for inclusion of drug-resistant M. tuberculosis isolates (N = 4/18). Based on our clinical routine the fluorescence-based liquid media system BACTEC MGIT 960 was used for susceptibility testing of nitroxoline and mainstay antitubercular drugs. Nitroxoline yielded a MIC90 of 4 mg/L for MTBC. In all M. tuberculosis isolates nitroxoline MICs were at least two twofold dilutions below the current EUCAST susceptibility breakpoint of <= 16 mg/L (limited to E. coli and uncomplicated UTI). In vitro activity of nitroxoline can be considered excellent, even in multidrug-resistant isolates. Future studies with in vivo models should evaluate a potential role of nitroxoline in the treatment of tuberculosis in the era of drug resistance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Hoffmann, Ada Marie UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolke, Martina UNSPECIFIED UNSPECIFIED UNSPECIFIED Rybniker, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Plum, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Fuchs, Frieder UNSPECIFIED orcid.org/0000-0001-7075-5378 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-674700
DOI:	10.3389/fphar.2022.906097
Journal or Publication Title:	Front. Pharmacol.
Volume:	13
Date:	2022
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1663-9812
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EPIDEMIOLOGY; THERAPY; AGENTS Multiple languages Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67470