Metabolised Antibiotics: An Overlooked Driver of Antimicrobial Resistance Comparable to Their Parent Compounds

Antimicrobial resistance (AMR) is one of the leading global public health threats of the twenty-first century, and the environment, particularly wastewater and receiving waterways, is increasingly recognised as an important arena in which resistance is selected and disseminated. Attention has traditionally been focused on parent antibiotic compounds discharged into the environment, while the transformation products generated when antibiotics are metabolised in the human body or degraded during wastewater treatment have received comparatively little scrutiny. In this review, current evidence is synthesised, anchored by a 2026 study from the University of Queensland and the University of Exeter, indicating that antibiotic transformation products can exert selective pressure for resistance that is comparable to, and in some cases stronger than, that exerted by their parent compounds. Using wastewater-derived microbial communities from Brisbane, Australia, and Falmouth, United Kingdom, it was demonstrated that transformation products of fluoroquinolones, macrolide-lincosamide-streptogramin antibiotics and sulfonamides enriched the class 1 integron-integrase gene intI1, a recognised marker of anthropogenic selection for resistance, at levels similar to the parent drugs. The pharmacokinetic and environmental origins of antibiotic transformation products are discussed, along with the mechanistic basis for resistance selection at sub-inhibitory concentrations, the implications of these findings for environmental risk assessment and AMR surveillance frameworks, and the limitations of current wastewater treatment in mitigating this hidden reservoir of bioactivity. It is concluded that transformation products should no longer be excluded from AMR monitoring and regulatory frameworks, and priority areas for future research are outlined.