(Fluoro)quinolones and quinolone resistance genes in the aquatic environment: A river catchment perspective.

This study provides an insight into the prevalence of (fluoro)quinolones (FQs) and their specific quinolone qnrS resistance gene in the Avon river catchment area receiving treated wastewater from 5 wastewater treatment plants (WWTPs), serving 1.5 million people and accounting for 75% of inhabitants living in the catchment area in the South West of England.. Ofloxacin, ciprofloxacin, nalidixic acid and norfloxacin were found to be ubiquitous with daily loads reaching a few hundred g/day in wastewater influent and tens of g/day in receiving waters. This was in contrast to other FQs analysed: flumequine, nadifloxacin, lomefloxacin, ulifloxacin, prulifloxacin, besifloxacin and moxifloxacin, which were hardly quantified. Enantiomeric profiling revealed that ofloxacin was enriched with the S-(-)-enantiomer, likely deriving from its prescription as the more potent enantiomerically pure levofloxacin, alongside racemic ofloxacin. While ofloxacin's enantiomeric fraction (EF) remained constant, high stereoselectivity was observed in the case of its metabolite ofloxacin-N-oxide. The removal efficiency of quinolones during wastewater treatment at 5 WWTPs utilising either trickling filters (TF) or activated sludge (AS), was compound and wastewater treatment process dependent, with AS providing better efficiency than TF. The qnrS resistance gene was ubiquitous in wastewater. Its removal was WWTP treatment process dependent with TF performing best and resulting in significant removal of the gene (from 28 to 75%). AS underperformed with only 9% removal in the case of activated sludge and actual increase in the gene copy number within sequencing batch reactors (SBRs). Interestingly, the data suggests that higher removal of antibiotics could be linked with high prevalence of the gene (SBR and WWTP E) and vice versa, low removal of antibiotic is correlated with lower prevalence of the gene in wastewater effluent (TF, WWTP B and D). This is especially prominent in the case of ofloxacin and could indicate that AS might be facilitating antimicrobial resistance (AMR) prevalence to higher extent than TF. Wastewater-based epidemiology (WBE) was also applied to monitor any potential misuse (e.g. direct disposal) of FQs in the catchment. In most cases higher use of antibiotics with respect to official statistics (i.e. ciprofloxacin, ofloxacin) was observed, which suggests that FQs management practice require further attention.

Wastewater-based epidemiology combined with local prescription analysis as a tool for temporalmonitoring of drugs trends - A UK perspective.

This paper reports the application of wastewater-based epidemiology (WBE) for the monitoring of one city in the UK in years 2014-2018 as a means of 1) exploring relative temporal changes of illicit drug usage trends across 5 sampling weeks in 5 years, (2) assessing policy impact in reducing drug consumption, focussing particularly on mephedrone, which was classified as a class B drug in the UK in 2010, and the effects of subsequent regulation such as the novel psychoactive substances (NPS) bill of 2016, (3) investigating temporal changes in consumption of prescription pharmaceuticals vs illicit drug usage, and (4) comparing consumption of prescription drugs with WBE to enable more accurate verification of prescription drugs with abuse potential. Mephedrone was quantified only for the first two years of the study, 2014-2015, and remained undetected for the next three years of the study. This shows that given enough time changes in drug policy can have an effect on drug consumption. However, after the introduction of the 2016 NPS bill, between the third and fourth study years, there was an observable increase in the consumption of "classic" drugs of abuse such as cocaine, MDMA and ketamine suggesting a shift away from novel psychoactives. The unique prescription dataset allowed for a more accurate calculation of heroin consumption using morphine by examining other sources morphine. Additionally, for compounds with controlled prescription like methadone, trends in consumption estimated by wastewater and trends in prescription correlated. Wastewater-based epidemiology is a powerful tool for examining whole populations and determining the efficacy and direction of government actions on health, as it can, alongside prescription and wider monitoring data, provide a clear insight into what is being consumed by a population and what action is needed to meet required goals.

Enantioselective fractionation of fluoroquinolones in the aqueous environment using chiral liquid chromatography coupled with tandem mass spectrometry.

This paper aims to examine the multiresidue enantiomeric profiling of (fluoro)quinolones and their metabolites in solid and liquid environmental matrices using chiral HPLC-MS/MS method and a CHIRALCEL® OZ-RH column. Simultaneous chiral separation was obtained for chiral ofloxacin and its main metabolites ofloxacin-N-oxide and desmethyl-ofloxacin; moxifloxacin; the prodrug prulifloxacin and its active compound ulifloxacin; flumequine; nadifloxacin and R-(+)-besifloxacin. Achiral antibiotics (ciprofloxacin, norfloxacin and nalidixic acid) were also included in the method to enable the analysis of all targeted quinolones within one analytical run. Satisfactory enantiomeric resolution (Rs ≥ 1) was obtained for five out of eight chiral drugs enabling quantitative analysis. The overall performance of the method was satisfactory with a method precision <20%, relative recoveries >70% for most of the analytes and method detection limits (MDL) at low ng L-1 levels (0.1 < MDL (ng L-1)< 6.4, 0.1 < MDL (ng L-1)< 6.6 and 0.1 < MDL (ng L-1)< 7.0 in influent, effluent and river waters for 83% compounds, 0.01 < MDL (ng g-1)< 4.9 in solids for 91% compounds). Enantiomeric profiling from a week-long monitoring campaign in the UK showed that (±)-ofloxacin was found to be racemic in upstream waters but it was enriched with S-(-)-enantiomer in wastewater and in receiving waters. This could be due to the fact that ofloxacin can be used both as a racemate and as a S-(-)-enantiomer. Its consumption was further confirmed by the chiral signature of the investigated ofloxacin metabolites. As a result, alterations in the enantiomeric composition of antibiotics could influence not only their activity and toxicity in the environment, but also could induce changes in the microbial communities constantly exposed to them.