A process-resolved risk prioritization framework reveals hidden antibiotic control deficiencies in wastewater treatment trains.

Antibiotic prioritization in wastewater treatment plants (WWTPs) commonly relies on influent-effluent changes. Such assessments may mask differences among configurations, treatment contexts, and endpoint media. Here, we established a process-resolved antibiotic Environmental Health Prioritization index (PA-EHPi). At the configuration × antibiotic scale, PA-EHPi integrates effluent occurrence, apparent removal, ecological risk, and antimicrobial resistance selection pressure. Across anaerobic-anoxic-oxic (AAO), sequencing batch reactor (SBR), and membrane bioreactor (MBR) treatment configurations with broadly comparable influent antibiotic profiles and conventional pollutant removals, PA-EHPi revealed distinct priority profiles. PA-EHPi identified 2 of 22 antibiotics as priorities in AAO, 9 of 26 in SBR, and 9 of 24 in MBR. Azithromycin and clarithromycin remained priorities across all three configurations. Treatment-train diagnosis further revealed stable apparent removal in the sampled AAO plants, fluctuating removal in SBR plants, and significant terminal rebound in MBR plants. Linking PA-EHPi with sludge partitioning and antibiotic resistance gene profiles translated effluent priorities into endpoint-specific management pathways, identifying quinolones as dual effluent-sludge concerns, macrolides as effluent residual targets, tetracyclines as sludge-associated concerns, and chloramphenicols as resistance-background monitoring targets. Overall, the established PA-EHPi extends static effluent ranking into a process- and endpoint-resolved diagnostic framework, helping identify priority targets for antibiotic control and multimedia management in WWTPs.