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

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

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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.

Original language	English
Article number	115653
Pages (from-to)	115653
Journal	Water Research
Volume	175
Early online date	10 Mar 2020
DOIs	https://doi.org/10.1016/j.watres.2020.115653
Publication status	Published - 15 May 2020

Bibliographical note

Funding

This work was supported by the European Union’s Seventh Framework Programme for Research, Technological Development and Demonstration [grant agreement 317205 , the SEWPROF MC ITN project, ‘A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level’] and by Natural Environment Research Council Project on ‘Impact of stereochemistry of antimicrobial agents on their environmental fate, biological potency and the emergence of resistance’ [grant NE/N019261/1 ]. Wastewater samples were provided by local WWTPs to the University of Bath (United Kingdom) by: Wessex Water, Norwegian Institute for Water Research (Norway), Swiss Federal Institute of Aquatic Science and Technology (Switzerland), Technical University of Denmark (Denmark), Mario Negri Institute for Pharmacological Research (Italy), KWR Watercycle Research Institute (The Netherlands), University Jaume I (Spain). Erika Castrignanò and Barbara Kasprzyk-Hordern planned and designed the study. Erika Castrignanò, Zhugen Yang, 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 and Barbara Kasprzyk-Hordern organised the collection of the wastewater samples. Erika Castrignanò prepared and analysed the samples. Erika Castrignanò and Barbara Kasprzyk-Hordern interpreted the results, drafted the manuscript, which was critically revised by all co-authors. Jose A. Baz-Lomba from Norwegian Institute for Water Research (NIVA), Christoph Ort and Ann-Katrin McCall from Eawag are acknowledged for help with sample provision.

Keywords

Animals
Anti-Bacterial Agents
Cities
Drug Resistance, Bacterial
Europe
Humans
Quinolones
Waste Water

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.watres.2020.115653

EC et al Europe AMR repositoryAccepted author manuscript, 756 KBLicence: CC BY-NC-ND

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Castrignanò, E., Yang, Z., Feil, E. J., Bade, R., Castiglioni, S., Causanilles, A., Gracia-Lor, E., Hernandez, F., Plósz, B. G., Ramin, P., Rousis, N. I., Ryu, Y., Thomas, K. V., de Voogt, P., Zuccato, E., & Kasprzyk-Hordern, B. (2020). Enantiomeric profiling of quinolones and quinolones resistance gene qnrS in European wastewaters. Water Research, 175, 115653. Article 115653. https://doi.org/10.1016/j.watres.2020.115653

Castrignanò, E, Yang, Z, Feil, EJ, Bade, R, Castiglioni, S, Causanilles, A, Gracia-Lor, E, Hernandez, F, Plósz, BG, Ramin, P, Rousis, NI, Ryu, Y, Thomas, KV, de Voogt, P, Zuccato, E & Kasprzyk-Hordern, B 2020, 'Enantiomeric profiling of quinolones and quinolones resistance gene qnrS in European wastewaters', Water Research, vol. 175, 115653, pp. 115653. https://doi.org/10.1016/j.watres.2020.115653

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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 Castell{\'o}n 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.",

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AU - Causanilles, Ana

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AU - Hernandez, Felix

AU - Plósz, Benedek G.

AU - Ramin, Pedram

AU - Rousis, Nikolaos I.

AU - Ryu, Yeonsuk

AU - Thomas, Kevin V.

AU - de Voogt, Pim

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N2 - 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.

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Embargoed Document

Fingerprint

Impact of Stereochemistry of Antimicrobial Agents on their Environmental Fate, Biological Potency and the Emergence of Resistance

Marie Curie ITN - SEWPROF A New Paradigm in Drug Use and Human Health Risk Assessment: Sewage Profiling at the Community Level management

Cite this

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

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

Other files and links

Embargoed Document

Fingerprint

Projects

Impact of Stereochemistry of Antimicrobial Agents on their Environmental Fate, Biological Potency and the Emergence of Resistance

Marie Curie ITN - SEWPROF A New Paradigm in Drug Use and Human Health Risk Assessment: Sewage Profiling at the Community Level management

Cite this