Widespread selection of antibiotic resistance within hospital sewers

Environmental microbiomes are sources of diverse antibiotic resistance determinants that can be mobilized and transferred to human pathogens under a selection pressure from antibiotics. Hospital sewers contain more antibiotics than most environments and are thus increasingly recognised as potential arenas for resistance evolution. However, it is unknown if resistance selection occurs there and what the drivers are. Here we show selection of antibiotic-resistant bacteria within Swedish hospital sewers. Evidence include; consistent selection of multiple resistances in Escherichia coli exposed to filtered wastewater from ten hospitals, but not to corresponding municipal wastewaters; in-situ enrichment of resistant over sensitive E. coli from wastewater to sewer biofilms at hospitals, but not at municipal sites; and higher resistance in bacteria collected from hospital sewers than from municipal sites as assessed by culturing and metagenomics. Evidence for drivers includes complete rescue of sensitive E. coli by addition of resistance genes to fluoroquinolones and β-lactams, and cellular effects typical for β-lactams. Measured concentrations by liquid-chromatography-tandem-mass-spectrometry compared to selective thresholds identify ciprofloxacin and cefotaxime as principal selective agents. Antibiotic concentrations and use data allow extrapolation of risks beyond Sweden. Given the absence of detectable selection at municipal sites, mitigations of risks in hospital sewers should be prioritized.