Frieder Fuchs1, Herbert Hof2, Sandra Hofmann2, Oliver Kurzai3, Jacques F Meis4, Axel Hamprecht5. 1. Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Medical Faculty and University Hospital of Cologne, Cologne, Germany. 2. MVZ Labor Limbach und Kollegen, Heidelberg, Germany. 3. National Reference Centre for Invasive Fungal Infections (NRZMyk), Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Jena, Germany; Institute for Hygiene and Microbiology, University Wuerzburg, Wuerzburg, Germany. 4. Department of Medical Microbiology and Infectious Diseases, Excellence Centre for Medical Mycology (ECMM), Centre of Expertise in Mycology Radboudumc/CWZ, Canisius Wilhelmina Hospital, Nijmegen, the Netherlands; Bioprocess Engineering and Biotechnology Graduate Programme, Federal University of Paraná, Curitiba, Brazil. 5. Institute for Medical Microbiology, Immunology and Hygiene, University of Cologne, Medical Faculty and University Hospital of Cologne, Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Institute for Medical Microbiology and Virology, University of Oldenburg, Oldenburg, Germany. Electronic address: axel.hamprecht@uol.de.
Abstract
OBJECTIVES: To investigate the in vitro activity of nitroxoline against a molecularly characterized collection of clinical Candida auris isolates. METHODS: Thirty-five clinical isolates of C. auris from diverse sources representing all five different C. auris clades were included in the study. Nitroxoline activity was assessed using broth microdilution. Additionally, susceptibility testing by disc diffusion was assessed on RPMI-1640 and Müller-Hinton agar plates. Minimal inhibitory concentrations of the antifungals fluconazole, voriconazole, amphotericin B and anidulafungin were determined. RESULTS: Nitroxoline MICs ranged from 0.125 to 1 mg/L (MIC50/90 0.25/0.5 mg/L). Compared with amphotericin B (MIC >1 mg/L in 4/35 isolates), anidulafungin (MIC >0.06 mg/L in 26/35 isolates) and fluconazole (MIC >4 mg/L in 31/35 isolates), in vitro activity of nitroxoline was high. Isolates belonging to clade I had marginally lower nitroxoline MICs (range 0.125-0.5 mg/L, mean MIC 0.375 mg/L) compared with clade III (range 0.5-1 mg/L, mean MIC 0.7 mg/L; p = 0.0094). The correlation of MIC and inhibition zones by disc diffusion was good when using RPMI-agar for disc diffusion, with a Pearson's correlation coefficient of -0.74 (95% CI -0.86 to -0.54). CONCLUSIONS: Nitroxoline has excellent in vitro activity against C. auris isolates, with MICs of 0.125-1 mg/L (for comparison, the EUCAST breakpoint for uncomplicated urinary tract infection with Escherichia coli is ≤ 16 mg/L). It is an approved, well-tolerated antimicrobial that achieves high urinary concentrations after oral administration and could be a useful treatment option in C. auris candiduria.
OBJECTIVES: To investigate the in vitro activity of nitroxoline against a molecularly characterized collection of clinical Candida auris isolates. METHODS: Thirty-five clinical isolates of C. auris from diverse sources representing all five different C. auris clades were included in the study. Nitroxoline activity was assessed using broth microdilution. Additionally, susceptibility testing by disc diffusion was assessed on RPMI-1640 and Müller-Hinton agar plates. Minimal inhibitory concentrations of the antifungals fluconazole, voriconazole, amphotericin B and anidulafungin were determined. RESULTS: Nitroxoline MICs ranged from 0.125 to 1 mg/L (MIC50/90 0.25/0.5 mg/L). Compared with amphotericin B (MIC >1 mg/L in 4/35 isolates), anidulafungin (MIC >0.06 mg/L in 26/35 isolates) and fluconazole (MIC >4 mg/L in 31/35 isolates), in vitro activity of nitroxoline was high. Isolates belonging to clade I had marginally lower nitroxoline MICs (range 0.125-0.5 mg/L, mean MIC 0.375 mg/L) compared with clade III (range 0.5-1 mg/L, mean MIC 0.7 mg/L; p = 0.0094). The correlation of MIC and inhibition zones by disc diffusion was good when using RPMI-agar for disc diffusion, with a Pearson's correlation coefficient of -0.74 (95% CI -0.86 to -0.54). CONCLUSIONS: Nitroxoline has excellent in vitro activity against C. auris isolates, with MICs of 0.125-1 mg/L (for comparison, the EUCAST breakpoint for uncomplicated urinary tract infection with Escherichia coli is ≤ 16 mg/L). It is an approved, well-tolerated antimicrobial that achieves high urinary concentrations after oral administration and could be a useful treatment option in C. auris candiduria.
Authors: Frieder Fuchs; Alexander Maximilian Aldejohann; Ada Marie Hoffmann; Grit Walther; Oliver Kurzai; Axel G Hamprecht Journal: Antimicrob Agents Chemother Date: 2022-05-11 Impact factor: 5.938