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

Abstract

This study provides an insight into the prevalence of (fluoro)quinolones (FQs) and their specific quinolone qnrS resistance gene in the aquatic environment from 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. FQs were analysed by stereoselective chiral chromatography and tandem mass spectrometry and their specific qnrS resistance gene was measured with digital PCR, which allowed for spatiotemporal evaluation of the prevalence of FQs and qnrS across the catchment. 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 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.

Allogenous Selection of Mutational Collateral Resistance: Old Drugs Select for New Resistance Within Antibiotic Families

“…Nalidixic acid is used in South-East Asian countries mainly to treat Shigella infections (Hoge et al, 1995). Today, nalidixic acid is still consistently found in European rivers (Castrignanò et al, 2020), and pipemidic acid is consistently present in European wastewater treatment plants (Rodriguez-Mozaz et al, 2020), and possibly will continue to serve as selectors for resistance to the newest fluoroquinolones. Similarly, exposure to fluoroquinolones such as ciprofloxacin and ofloxacin typically selects mutants that show increased resistance to these drugs, but even higher levels of resistance to more recent fluoroquinolones, such as sparfloxacin.…”

Allogenous Selection of Mutational Collateral Resistance: Old Drugs Select for New Resistances Within Antibiotic Families

“…Nalidixic acid is used in South-East Asian countries mainly to treat Shigella infections (Hoge et al, 1995). Today, nalidixic acid is still consistently found in European rivers (Castrignanò et al, 2020) and will continue to serve as a selector for resistance to the newest fluoroquinolones. Similarly, exposure to second-generation fluoroquinolones such as ciprofloxacin and ofloxacin typically selects mutants that show increased resistance to these drugs, but even higher levels of resistance to more recent fluoroquinolones, such as sparfloxacin (a thirdgeneration fluoroquinolone).…”

Enhanced Biosynthesis of Fatty Acids Is Associated with the Acquisition of Ciprofloxacin Resistance in Edwardsiella tarda

“…However, the extensive use of quinolone antibiotics leads to the emergence of drug-resistant bacteria ( 18 , 19 ), and the numbers of clinically isolated multidrug-resistant strains are increasing ( 20 – 22 ). Furthermore, the horizontal gene transfer of multiple drug resistance genes and intertransmissions of drug resistance genes between microorganisms with direct human association are subjects of huge concern ( 23 , 24 ).…”