Antibiotic transformation products exert selective pressure for antimicrobial resistance comparable to parent compounds

Antibiotic transformation products (TPs) are frequently detected in wastewater and aquatic environments, yet their role in selecting for antimicrobial resistance (AMR) remains largely unexplored. Despite environmental persistence, mobility and potential residual bioactivity, TPs are routinely excluded from environmental risk assessment and AMR surveillance frameworks. Here we systematically assess the resistance-selecting potential of antibiotic TPs relative to their parent compounds, using complex wastewater-derived microbial communities. A growth-based assay revealed that several TPs had lowest observed effect concentrations only twofold higher than their parents, with moxifloxacin sulfate and descladinose roxithromycin even exhibiting stronger growth inhibition compared with their respective parent antibiotics. Seven-day evolution experiments showed that TPs such as desmethyl ofloxacin, N-acetyl sulfamethoxazole and desmethyl erythromycin enriched the class 1 integron gene intI1 at levels comparable to or exceeding those of their parent antibiotics, across fluoroquinolone, sulfonamide and macrolide–lincosamide–streptogramin classes. These findings show that TPs constitute a substantial, overlooked component of total selective pressure in wastewater systems and should be incorporated into AMR surveillance, treatment evaluation and environmental risk assessment frameworks.