Quantifying community-wide antimicrobials usage via wastewater-based epidemiology

Increasing usage of antimicrobials is a significant contributor to the emergence and dissemination of antimicrobial resistance. Wastewater-based epidemiology is a useful tool for evaluating public health, via the monitoring of chemical and biological markers in wastewater influent, such as antibiotics. Chemical analyses are used to determine sampled drug concentrations; measured daily flows then enable quantitation of analyte mass/day; and population estimates are utilised to calculate mass/day/1000inhabitants. These data allow for effective evaluations of drug presence and temporal trends, but do not fully represent the total quantity of drugs being consumed, i.e., human intake. Factors such as drug metabolism and physiochemical stability significantly decrease the quantity of parent drug that reaches wastewater treatment plants, leading to potential underestimations of community usage. A case study of 16 antimicrobials, and their metabolites was conducted in this study: including sulfonamides, trimethoprim, metronidazole, quinolones, nitrofurantoin, cyclines, and antiretrovirals. Correction factors (CFs) for human drug excretion, for various metabolite forms, were determined via a systematic literature review of pharmacokinetic research. Analyte stability was examined over a 24 h study. The estimation of community-wide drug intake was evaluated using the associated catchment prescription data. Overall, antimicrobials excreted in an unchanged form were often observed to over-estimate daily intake. This could be attributed to biotransformation, e.g., via glucuronide cleavage, or direct disposal of unused drugs. Acetyl-sulfonamides, trimethoprim, hydroxy-metronidazole, clarithromycin, ciprofloxacin, ofloxacin, tetracycline, and oxytetracycline generally performed well in the estimation of drug intake, relative to prescription records. The low prevalence of quinolone and trimethoprim metabolites, and the low stability of nitrofurantoin, limited the ability to evaluate these metabolites and their respective CFs. CFs established in the systematic literature review could not be validated for some metabolites in the case study due to lack of available prescription data (lamivudine, emtricitabine); an inability to quantify biomarkers (nitrofurantoin, doxycycline); being excreted at too low levels (hydroxy-trimethoprim, ofloxacin-N-oxide, desethylene-ciprofloxacin); or insufficient pharmacokinetic literature sources (the nitrofurantoin metabolite, NPAHD). Further work is currently underway to apply established CFs in other catchment with higher prevalence of antimicrobials usage.