Abstract

Antibiotic resistance surveillance through regional and up-to-date testing of clinical isolates is a foundation for implementing effective empirical treatment. Surveillance data also provides an overview of geographical and temporal changes that are invaluable for guiding interventions. Still, due to limited infrastructure and resources, clinical surveillance data is lacking in many parts of the world. Given that sewage is largely made up of human fecal bacteria from many people, sewage epidemiology could provide a cost-efficient strategy to partly fill the current gap in clinical surveillance of antibiotic resistance. Here we explored the potential of sewage metagenomic data to assess clinical antibiotic resistance prevalence using environmental and clinical surveillance data from across the world. The sewage resistome correlated to clinical surveillance data of invasive Escherichia coli isolates, but none of several tested approaches provided a sufficient resolution for clear discrimination between resistance towards different classes of antibiotics. However, in combination with socioeconomic data, the overall clinical resistance situation could be predicted with good precision. We conclude that analyses of bacterial genes in sewage could contribute to informing management of antibiotic resistance.

Highlights

  • Antibiotic resistance surveillance through regional and up-to-date testing of clinical isolates is a foundation for implementing effective empirical treatment

  • We investigated the correlation between reported clinical resistance prevalence in bloodstream infections of E. coli or an aggregated resistance index from[16] and either (1) total antibiotic resistance genes (ARGs), (2) total ARGs for each antibiotic class separately, (3) the 10 most abundant ARGs that are known to be present in the E. coli pangenome, (4) the 10 most abundant E. coli ARGs separated by antibiotic class, (5) IntI1 integron gene abundances in sewage

  • We explored the possibility to use country level relative abundance of ARGs in sewage metagenomic data to predict country level proportion of antibiotic-resistant clinical isolates

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Summary

Introduction

Antibiotic resistance surveillance through regional and up-to-date testing of clinical isolates is a foundation for implementing effective empirical treatment. Traditional surveillance data are based on data from a large number of clinical isolates, each subjected to susceptibility testing with standardized methods As this approach is labor intensive, expensive and needs specialized infrastructure[2], surveillance data are lacking or very limited in many parts of the world, not least in low- and middle-income countries[3]. Sewage epidemiology has been proposed as an alternative or complementary method to overcome some of the challenges in antibiotic resistance surveillance, the need for extensive patient sampling and the limited resources and infrastructure in low- and middle-income countries. A large number of isolates can be efficiently collected and managed as recently indicated by a global monitoring of cefotaxime-resistant coliforms from sewage[13], this approach can be as labor intensive as clinical surveillance with regard to the susceptibility testing part. These include (1) prediction from genotype to phenotype (2) challenge to identify point mutations leading to antibiotic resistance, (3)

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