{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:00:00Z","timestamp":1787061600957,"version":"build-2736575974"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T00:00:00Z","timestamp":1653523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Antimicrobial treatment options for mycobacterial infections are limited due to intrinsic resistance and the emergence of acquired resistance in\n                    <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n                    . 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\n                    <jats:italic>in vitro<\/jats:italic>\n                    activity of nitroxoline against 18 clinical isolates of\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    complex (MTBC) (\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    N = 16,\n                    <jats:italic>M. bovis<\/jats:italic>\n                    BCG N = 1,\n                    <jats:italic>M. bovis<\/jats:italic>\n                    sp.\n                    <jats:italic>bovis<\/jats:italic>\n                    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\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    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 MIC\n                    <jats:sub>90<\/jats:sub>\n                    of 4\u00a0mg\/L for MTBC. In all\n                    <jats:italic>M. tuberculosis<\/jats:italic>\n                    isolates nitroxoline MICs were at least two twofold dilutions below the current EUCAST susceptibility breakpoint of \u226416\u00a0mg\/L (limited to\n                    <jats:italic>E. coli<\/jats:italic>\n                    and uncomplicated UTI).\n                    <jats:italic>In vitro<\/jats:italic>\n                    activity of nitroxoline can be considered excellent, even in multidrug-resistant isolates. Future studies with\n                    <jats:italic>in vivo<\/jats:italic>\n                    models should evaluate a potential role of nitroxoline in the treatment of tuberculosis in the era of drug resistance.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.906097","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T10:46:50Z","timestamp":1654080410000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["In vitro Activity of Repurposed Nitroxoline Against Clinically Isolated Mycobacteria Including Multidrug-Resistant Mycobacterium tuberculosis"],"prefix":"10.3389","volume":"13","author":[{"given":"Ada Marie","family":"Hoffmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Wolke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Rybniker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Plum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frieder","family":"Fuchs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/j.ijantimicag.2016.10.017","article-title":"Nitroxoline: A Broad-Spectrum Biofilm-Eradicating Agent against Pathogenic Bacteria","volume":"49","author":"Abouelhassan","year":"2017","journal-title":"Int. J. Antimicrob. Agents."},{"key":"B2","unstructured":"BACTECTM MGITTM 960 SIRE Kits for the Antimycobacterial Susceptibility Testing of Mycobacterium tuberculosis1182010"},{"key":"B3","first-page":"565","article-title":"Mycobacteria: Laboratory Methods for Testing Drug Sensitivity and Resistance","volume":"29","author":"Canetti","year":"1963","journal-title":"Bull. World Health Organ"},{"key":"B4","volume-title":"M24_3E: Susceptibility Testing of Mycobacteria, Nocardia spp., and Other Aerobic Actinomycetes","year":""},{"key":"B5","volume-title":"M62_1E: Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia Spp and Other Aerobic Actinomycetes1st CLSI Supplement M62","year":""},{"key":"B6","first-page":"207","article-title":"De le Penetration de la Nitroxoline dans le parenchyme prostatique : Essai therapeutique","volume":"3","author":"Dufour","year":"1979","journal-title":"J. Urol. Nephrol."},{"key":"B7","article-title":"The European Committee on Antimicrobial Susceptibility Testing","volume-title":"Breakpoint Tables for Interpretation of MICs and Zone Diameters","year":"2021"},{"key":"B8","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1016\/j.cmi.2017.11.007","article-title":"Nitroxoline in Geriatric Patients with Lower Urinary Tract Infection Fails to Achieve Microbiologic Eradication: A Noncomparative, Prospective Observational Study","volume":"24","author":"Forstner","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"B9","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1111\/J.1432-1033.1974.TB03597.X","article-title":"Rapid and Selective Inhibition of RNA Synthesis in Yeast by 8-Hydroxyquinoline","volume":"46","author":"Fraser","year":"1974","journal-title":"Eur. J. Biochem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2934","DOI":"10.1093\/JAC\/DKZ275","article-title":"Susceptibility of Carbapenemase-Producing Enterobacterales (CPE) to Nitroxoline","volume":"74","author":"Fuchs","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1697.e7","DOI":"10.1016\/j.cmi.2021.06.035","article-title":"Antifungal Activity of Nitroxoline against Candida Auris Isolates","volume":"27","author":"Fuchs","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"B12","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1099\/jmm.0.001014","article-title":"In Vitro activity of Mecillinam and Nitroxoline against Neisseria Gonorrhoeae - Re-Purposing Old Antibiotics in the Multi-Drug Resistance Era","volume":"68","author":"Fuchs","year":"2019","journal-title":"J. Med. Microbiol."},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkac123","article-title":"In Vitro activity of Nitroxoline against Carbapenem-Resistant Acinetobacter Baumannii Isolated from the Urinary Tract","author":"Fuchs","year":"","journal-title":"J. Antimicrob. Chemother."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1128\/aac.02265-21","article-title":"In Vitro Activity of Nitroxoline in Antifungal Resistant Candida Species Isolated from the Urinary Tract","author":"Fuchs","year":"","journal-title":"Antimicrob. Agents Chemother."},{"key":"B15","doi-asserted-by":"publisher","first-page":"34974","DOI":"10.1021\/acsami.8b12812","article-title":"Albumin-Stabilized Metal-Organic Nanoparticles for Effective Delivery of Metal Complex Anticancer Drugs","volume":"10","author":"Hu","year":"2018","journal-title":"ACS Appl. Mater. Interfaces."},{"key":"B16","doi-asserted-by":"publisher","first-page":"16349","DOI":"10.1021\/acs.jmedchem10.1021\/acs.jmedchem.1c01318","article-title":"Novel Antimicrobial 8-Hydroxyquinoline-Based Agents: Current Development, Structure-Activity Relationships, and Perspectives","volume":"2564","author":"Joaquim","year":"2021","journal-title":"J. Med. Chem."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4335","DOI":"10.1128\/AAC.49.10.4335-4338.2005","article-title":"Oral Therapy Using Nanoparticle-Encapsulated Antituberculosis Drugs in guinea Pigs Infected with Mycobacterium tuberculosis","volume":"49","author":"Johnson","year":"2005","journal-title":"Antimicrob. Agents. Chemother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1007\/s00120-017-0389-1","article-title":"Epidemiology, Diagnostics, Therapy, Prevention and Management of Uncomplicated Bacterial Outpatient Acquired Urinary Tract Infections in Adult Patients : Update 2017 of the Interdisciplinary AWMF S3 Guideline","volume":"56","author":"Kranz","year":"2017","journal-title":"Urol. A"},{"key":"B19","doi-asserted-by":"publisher","first-page":"7019","DOI":"10.1128\/AAC.03946-14","article-title":"In Vitro activity of Nitroxoline against escherichia Coli Urine Isolates from Outpatient Departments in Germany","volume":"58","author":"Kresken","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B20","doi-asserted-by":"publisher","first-page":"19027","DOI":"10.18632\/oncotarget.3699","article-title":"Nitroxoline Impairs Tumor Progression In Vitro and In Vivo by Regulating Cathepsin B Activity","volume":"76","author":"Mirkovi\u0107","year":"2015","journal-title":"Oncotarget"},{"key":"B21","doi-asserted-by":"publisher","first-page":"550","DOI":"10.3390\/antibiotics9090550","article-title":"Novel Treatments Against Mycobacterium tuberculosis Based on Drug Repurposing","volume":"289","author":"Mourenza","year":"2020","journal-title":"Antibiot. (Basel)"},{"key":"B22","first-page":"476","article-title":"Clinical Pharmacokinetics of Nitroxoline","volume":"17","author":"Mrhar","year":"1979","journal-title":"Int. J. Clin. Pharmacol. Biopharm"},{"key":"B23","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1016\/S0924-8579(01)00437-X","article-title":"In Vitro activity of the Chelating Agents Nitroxoline and Oxine against Mycobacterium Bovis BCG","volume":"18","author":"Murugasu-Oei","year":"2001","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B24","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1186\/s12879-014-0628-7","article-title":"Review of the Literature and Individual Patients' Data Meta-Analysis on Efficacy and Tolerance of Nitroxoline in the Treatment of Uncomplicated Urinary Tract Infections","volume":"14","author":"Naber","year":"2014","journal-title":"BMC Infect. Dis."},{"key":"B25","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1002\/ddr.21531","article-title":"8-Hydroxyquinolines Are Bactericidal against Mycobacterium tuberculosis","volume":"80","author":"Odingo","year":"2019","journal-title":"Drug Dev. Res."},{"key":"B26","first-page":"455","article-title":"Direct Effect of Nitroxoline in the Inhibition of Bacterial Adherence to Urinary Catheters","volume":"38","author":"Oliviero","year":"1990","journal-title":"Pathol. Biol. Paris."},{"key":"B27","doi-asserted-by":"publisher","first-page":"457","DOI":"10.3201\/eid2503.180572","article-title":"Epidemiology of Extrapulmonary Tuberculosis Among Inpatients, China, 2008-2017","volume":"25","author":"Pang","year":"2019","journal-title":"Emerg. Infect. Dis."},{"key":"B28","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1128\/AAC.39.3.707","article-title":"Roles of Divalent Cations and pH in Mechanism of Action of Nitroxoline against Escherichia coli Strains","volume":"39","author":"Pelletier","year":"1995","journal-title":"Antimicrob. Agents Chemother."},{"key":"B29","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1039\/JR9540000570","article-title":"Some Quinoline-5 : 8-Quinones","author":"Petrow","year":"1954","journal-title":"J. Chem. Soc."},{"key":"B30","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1093\/jac\/dkz434","article-title":"Mutations that Increase Expression of the EmrAB-TolC Efflux Pump Confer Increased Resistance to Nitroxoline in Escherichia coli","volume":"75","author":"Pu\u00e9rtolas-Balint","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"5765","DOI":"10.1128\/AAC.00325-16","article-title":"8-Hydroxyquinolines Are Boosting Agents of Copper-Related Toxicity in Mycobacterium tuberculosis","volume":"60","author":"Shah","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"B33","volume-title":"MGIT Procedure Manual, Mycobacteria Growth Indicator Tube (MGIT) Culture and Drug Susceptibility Demonstration Projects","author":"Siddiqi","year":"2006"},{"key":"B34","doi-asserted-by":"publisher","first-page":"e00145","DOI":"10.1128\/JCM.00145-19","article-title":"Direct Detection of Pyrazinamide Resistance in Mycobacterium tuberculosis by Use of pncA PCR Sequencing","volume":"57","author":"Tam","year":"2019","journal-title":"J. Clin. Microbiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"346","DOI":"10.2174\/1871520619666190930124746","article-title":"Targeted Nanoparticles for Co-delivery of 5-FU and Nitroxoline, a Cathepsin B Inhibitor, in HepG2 Cells of Hepatocellular Carcinoma","volume":"20","author":"Varshosaz","year":"2020","journal-title":"Anticancer Agents Med. Chem."},{"key":"B36","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1128\/AAC.02147-13","article-title":"Urinary Concentrations and Antibacterial Activities of Nitroxoline at 250 Milligrams versus Trimethoprim at 200 Milligrams against Uropathogens in Healthy Volunteers","volume":"58","author":"Wagenlehner","year":"2014","journal-title":"Antimicrob. Agents. Chemother."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1128\/AAC.05894-11","article-title":"Reevaluation of the Critical Concentration for Drug Susceptibility Testing of Mycobacterium tuberculosis against Pyrazinamide Using Wild-type MIC Distributions and pncA Gene Sequencing","volume":"56","author":"Werngren","year":"2012","journal-title":"Antimicrob. Agents. Chemother."},{"key":"B38","volume-title":"Technical Manual for Drug Susceptibility Testing of Medicines Used in the Treatment of Tuberculosis","year":"2018"},{"key":"B39","volume-title":"Global Tuberculosis Report 2019Licence","year":"2020"},{"key":"B40","doi-asserted-by":"publisher","first-page":"2916","DOI":"10.1093\/jac\/dky255","article-title":"Review of the Pharmacokinetic Properties of Nitrofurantoin and Nitroxoline","volume":"73","author":"Wijma","year":"2018","journal-title":"J. Antimicrob. Chemother."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.906097\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T10:47:07Z","timestamp":1654080427000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.906097\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,26]]},"references-count":39,"alternative-id":["10.3389\/fphar.2022.906097"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.906097","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,26]]},"article-number":"906097"}}