Enantiomeric profiling of quinolones and quinolones resistance gene qnrS in European wastewaters

Erika Castrignanò; Zhugen Yang; Edward J Feil; Richard Bade; Sara Castiglioni; Ana Causanilles; Emma Gracia-Lor; Felix Hernandez; Benedek G Plósz; Pedram Ramin; Nikolaos I Rousis; Yeonsuk Ryu; Kevin V Thomas; Pim de Voogt; Ettore Zuccato; Barbara Kasprzyk-Hordern

doi:10.1016/j.watres.2020.115653

Enantiomeric profiling of quinolones and quinolones resistance gene qnrS in European wastewaters

Water Res. 2020 May 15:175:115653. doi: 10.1016/j.watres.2020.115653. Epub 2020 Mar 10.

Authors

Erika Castrignanò¹, Zhugen Yang², Edward J Feil³, Richard Bade⁴, Sara Castiglioni⁵, Ana Causanilles⁶, Emma Gracia-Lor⁷, Felix Hernandez⁸, Benedek G Plósz⁹, Pedram Ramin¹⁰, Nikolaos I Rousis¹¹, Yeonsuk Ryu⁸, Kevin V Thomas¹², Pim de Voogt¹³, Ettore Zuccato¹¹, Barbara Kasprzyk-Hordern¹⁴

Affiliations

¹ Department of Chemistry, Faculty of Science, University of Bath, Bath, BA2 7AY, United Kingdom; Department of Analytical, Environmental & Forensic Sciences, School of Population Health & Environmental Sciences, King's College London, London, SE1 9NH, United Kingdom.
² Department of Chemistry, Faculty of Science, University of Bath, Bath, BA2 7AY, United Kingdom; School of Water, Energy and Environment, Cranfield University, Cranfield, MK43 0AL, United Kingdom.
³ Department of Biology and Biochemistry, University of Bath, Bath, BA27AY, United Kingdom.
⁴ Research Institute for Pesticides and Water, University Jaume I, Avda. Sos Baynat s/n, E-12071, Castellón, Spain; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, 5000, Australia.
⁵ Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, P.O. Box 94248, 1090 GE, Amsterdam, the Netherlands.
⁶ KWR Watercycle Research Institute, Chemical Water Quality and Health, P.O. Box 1072, 3430 BB, Nieuwegein, the Netherlands; Institute for Biodiversity and Ecosystem Dynamics, University of Amsterdam, P.O. Box 94248, 1090 GE, Amsterdam, the Netherlands.
⁷ Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Department of Environmental Health Sciences, Via La Masa 19, 20156, Milan, Italy; Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, Avenida Complutense s/n, Madrid, Spain.
⁸ School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia 5000, Australia.
⁹ Department of Environmental Engineering, Technical University of Denmark, Bygningstorvet, Building 115, 2800, Kgs. Lyngby, Denmark; Department of Chemical Engineering, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom.
¹⁰ Department of Environmental Engineering, Technical University of Denmark, Bygningstorvet, Building 115, 2800, Kgs. Lyngby, Denmark; Process and Systems Engineering Center (PROSYS), Department of Chemical and Biochemical Engineering, Technical University of Denmark, Building 229, 2800, Kgs. Lyngby, Denmark.
¹¹ Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, 0349, Oslo, Norway.
¹² Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, 0349, Oslo, Norway; Queensland Alliance for Environmental Health Science (QAEHS), University of Queensland, 20 Cornwall Street, Woolloongabba, QLD, 4102, Australia.
¹³ Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Department of Environmental Health Sciences, Via La Masa 19, 20156, Milan, Italy; IBED-University of Amsterdam, the Netherlands.
¹⁴ Department of Chemistry, Faculty of Science, University of Bath, Bath, BA2 7AY, United Kingdom. Electronic address: b.kasprzyk-hordern@bath.ac.uk.

PMID: 32208173
DOI: 10.1016/j.watres.2020.115653

Abstract

Wastewater-based epidemiology (WBE) was applied for the first time in seven cities across Europe with the aim of estimating quinolones consumption via the analysis of human urinary metabolites in wastewater. This report is also the first pan-European study focussed on the enantiomeric profiling of chiral quinolones in wastewater. By considering loads of (fluoro)quinolones in wastewater within the context of human stereoselective metabolism, we identified cities in Southern Europe characterised by both high usage and direct disposal of unused ofloxacin. In Northern European cities, S-(-)-ofloxacin loads were predominant with respect to R-(+)-ofloxacin. Much more potent, enantiomerically pure S-(-)-ofloxacin was detected in wastewaters from Southern European cities, reflecting consumption of the enantiomerically pure antibiotic. Nalidixic acid, norfloxacin and lomefloxacin were detected in wastewater even though they were not prescribed according to official prescription data. S,S-(-)-moxifloxacin and S,S-(-)-moxifloxacin-N-sulphate were detected in wastewater due to metabolism of moxifloxacin. For the first time, average population-normalised ulifloxacin loads of 22.3 and 1.5 mg day^-1 1000 people^-1 were reported for Milan and Castellón as a result of prulifloxacin metabolism. Enrichment of flumequine with first-eluting enantiomer in all the samples indicated animal metabolism rather than its direct disposal. Fluoroquinolone loads were compared with qnrS gene encoding quinolone resistance to correlate usage of fluoroquinolone and prevalence of resistance. The highest daily loads of the qnrS gene in Milan corresponded with the highest total quinolone load in Milan proving the hypothesis that higher usage of quinolones is linked with higher prevalence of quinolone resistance genes. Utrecht, with the lowest quinolones usage (low daily loads) had also one of the lowest daily loads of the qnrS gene. However, a similar trend was not observed in Oslo nor Bristol where higher qnrS gene loads were observed despite low quinolone usage.

Keywords: (fluoro)quinolones; Antibiotic resistance; Biomarkers; Chiral antibiotics; Enantioselective analysis; Wastewater-based epidemiology.

MeSH terms

Animals
Anti-Bacterial Agents
Cities
Drug Resistance, Bacterial
Europe
Humans
Quinolones*
Wastewater*

Substances

Anti-Bacterial Agents
Quinolones
Waste Water