Secrets of the hospital underbelly: abundance of antimicrobial resistance genes in hospital wastewater reflects hospital antimicrobial use and inpatient length of stay

Abstract

Introduction\nHospital wastewater is a potential major source of antimicrobial resistance (AMR). This study uses metagenomics to ask how abundances of AMR genes in hospital wastewater are related to clinical activity. \nMethods\nSewage was collected over a 24-hour period from multiple wastewater collection points representing different specialties within a tertiary hospital site and simultaneously from community sewage works. High throughput shotgun sequencing was performed using Illumina HiSeq4000. AMR gene abundances were correlated to hospital antimicrobial usage (AMU), data on clinical activity and resistance prevalence in clinical isolates.\nFindings\nMicrobiota and AMR gene composition varied between each collection point and overall AMR gene abundance was higher in hospital wastewater than in community influent. The composition of AMR genes correlated with microbiota composition (Procrustes analysis, p=0.002). Increased antimicrobial consumption at a class level was associated with higher AMR gene abundance within that class in wastewater (incidence rate ratio 2.80, C.I. 1.2-6.5, p=0.016). Prolonged average patient length of stay was associated with higher total AMR gene abundance in wastewater (incidence rate ratio 2.05, C.I. 1.39-3.01, p=0.0003). AMR gene abundance at a class level within hospital wastewater did not reflect resistance patterns in the 181 clinical isolates grown from hospital inpatients over the time of wastewater sampling.\nConclusions\nHospital antimicrobial consumption and patient length of stay are important drivers of AMR gene outflow into the environment. Using metagenomics to identify the full range of AMR genes in hospital wastewater could represent a useful surveillance tool to monitor hospital AMR gene outflow and guide environmental policy on AMR.