Hospital wastewater as a hotspot for environmental dissemination of a carbapenem representative and enzyme inhibitors: insights from a multi-hospital study

Due to increasing antimicrobial resistance threatening social health stability, the World Health Organization classified anti-infectives into three groups, Access, Watch, and Reserve (AWaRe). The reserve list of antimicrobials, which are mainly used in hospitals as a last-resort option for the most severe infections, includes the carbapenems with enzyme inhibitors selected for this study. The purpose of this paper is to present the results of a comprehensive study of the prevalence of meropenem, cilastatin, and vaborbactam in the wastewater from 64 hospitals collected during two sampling seasons. Pharmaceuticals were present in the wastewater of more than 90% of the hospitals, in concentrations ranging between 1.20 and 17,315 ng/L. The findings of the statistical analyses revealed relationships between meropenem concentrations, annual intake, and hospital characteristics. A link was also visible between cilastatin wastewater levels and yearly imipenem consumption. Additionally, the impact of in situ chlorination was assessed, proving the ineffectiveness of the process regarding the possible removal of analytes. Preliminary calculations of the environmental risk assessment revealed a negligible impact of residues. A different outcome was seen for the risk evaluation for antimicrobial resistance selection. In more than half of the samples in which meropenem was determined, risk quotients reflected medium or high potential for development of antimicrobial resistance. Our results confirm the need for broader, systematic research on last-chance antimicrobials and show possibility of discovering more connections at the initial point of environmental introduction, which could help implement solutions to mitigate further spread of drug resistance.