Antimicrobial Transformation Products in the Aquatic Environment: Global Occurrence, Ecotoxicological Risks, and Potential of Antibiotic Resistance

The global spread of antimicrobial resistance (AMR) isconcerningfor the health of humans, animals, and the environment in a One Healthperspective. Assessments of AMR and associated environmental hazardsmostly focus on antimicrobial parent compounds, while largely overlookingtheir transformation products (TPs). This review lists antimicrobialTPs identified in surface water environments and examines their potentialfor AMR promotion, ecological risk, as well as human health and environmentalhazards using in silico models. Our review also summarizesthe key transformation compartments of TPs, related pathways for TPsreaching surface waters and methodologies for studying the fate ofTPs. The 56 antimicrobial TPs covered by the review were prioritizedvia scoring and ranking of various risk and hazard parameters. Mostdata on occurrences to date have been reported in Europe, while littleis known about antibiotic TPs in Africa, Central and South America,Asia, and Oceania. Occurrence data on antiviral TPs and other antibacterialTPs are even scarcer. We propose evaluation of structural similaritybetween parent compounds and TPs for TP risk assessment. We predicteda risk of AMR for 13 TPs, especially TPs of tetracyclines and macrolides.We estimated the ecotoxicological effect concentrations of TPs fromthe experimental effect data of the parent chemical for bacteria,algae and water fleas, scaled by potency differences predicted byquantitative structure-activity relationships (QSARs) for baselinetoxicity and a scaling factor for structural similarity. Inclusionof TPs in mixtures with their parent increased the ecological riskquotient over the threshold of one for 7 of the 24 antimicrobialsincluded in this analysis, while only one parent had a risk quotientabove one. Thirteen TPs, from which 6 were macrolide TPs, posed arisk to at least one of the three tested species. There were 12/21TPs identified that are likely to exhibit a similar or higher levelof mutagenicity/carcinogenicity, respectively, than their parent compound,with tetracycline TPs often showing increased mutagenicity. Most TPswith increased carcinogenicity belonged to sulfonamides. Most of theTPs were predicted to be mobile but not bioaccumulative, and 14 werepredicted to be persistent. The six highest-priority TPs originatedfrom the tetracycline antibiotic family and antivirals. This review,and in particular our ranking of antimicrobial TPs of concern, cansupport authorities in planning related intervention strategies andsource mitigation of antimicrobials toward a sustainable future.