Dynamic association of antimicrobial resistance in urinary isolates of Escherichia coli and Klebsiella pneumoniae between primary care and hospital settings in the Netherlands (2008–2020): a population-based study

Abstract

Background

It is unclear whether changes in antimicrobial resistance (AMR) in primary care influence AMR in hospital settings. Therefore, we investigated the dynamic association of AMR between primary care and hospitals.

Methods

We studied resistance percentages of Escherichia coli and Klebsiella pneumoniae isolates to co-amoxiclav, ciprofloxacin, fosfomycin, nitrofurantoin and trimethoprim submitted by primary care, hospital outpatient and hospital inpatient settings to the Dutch National AMR surveillance network (ISIS-AR) from 2008 to 2020. For each bacterium–antibiotic combination, we first conducted multivariable logistic regressions to calculate AMR odds ratios (ORs) by month and healthcare setting, adjusted for patient-related factors and a time term. Second, multiple time series analysis was done using vector autoregressive models including the (log) ORs for each bacterium–antibiotic combination. Models were interpreted by impulse response functions and Granger-causality tests.

Findings

The main AMR association was unidirectional from primary care to hospital settings with Granger-causality p-values between <0.0001 and 0.029. Depending on the bacterium–antibiotic combination, a 1% increase of AMR in E. coli and K. pneumoniae in primary care leads to an increase of AMR in hospital settings ranging from 0.10% to 0.40%. For ciprofloxacin resistance in K. pneumoniae, we found significant bidirectional associations between all healthcare settings with Granger-causality p-values between <0.0001 and 0.0075.

Interpretation

For the majority of bacterium–antibiotic combinations, the main AMR association was from primary care to hospital settings. These results underscore the importance of antibiotic stewardship at the community level.

Funding

ISIS-AR is supported by the Ministry of Health, Welfare and Sport of the Netherlands and the first author by the Central University of Ecuador to follow a PhD program in Erasmus MC.