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Introduction: NHS Lothian policy has recently changed to avoid first-line use of trimethoprim for uncomplicated urinary tract infections (UTI) in patients with risk factors for trimethoprim resistance, in line with national guidance. This study aimed to identify risk factors for antimicrobial resistance in Escherichia coli bacteraemia related to UTI. Methods: A retrospective cohort study of 687 patients with E. coli bacteraemia related to UTI in NHS Lothian from 01/02/18 to 29/02/20 was undertaken. Demographics and comorbidities were collected from electronic patient records. Community prescribing and microbiology data were collected from the prescribing information system and Apex. Univariate and multivariate analysis was undertaken using RStudio to analyse trimethoprim, gentamicin and multi-drug resistance (MDR). Results: Trimethoprim resistance was present in 282/687(41%) of blood culture isolates. MDR was present in 278/687(40.5%) isolates. Previous urinary trimethoprim resistant E. coli was a significant risk factor for both trimethoprim resistance (OR 9.44, 95%CI 5.83-15.9) and MDR (OR 4.81, 95%CI 3.17-7.43) on multivariate modelling. Trimethoprim prescription (OR 2.10, 95% CI 1.33-3.34) and the number of community antibiotic courses (OR 1.19, 95%CI 1.06-1.35) were additional risk factors for trimethoprim resistance. Multiple independent risk factors were also identified for trimethoprim resistance, MDR and gentamicin resistance. Discussion: This study showed a high prevalence of trimethoprim resistance and MDR in patients with E. coli bacteraemia related to UTI. This supports the withdrawal of trimethoprim from first-line treatment of UTIs in patients with risk factors for trimethoprim resistance. It has also identified risk factors for MDR in E. coli bacteraemia.
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Background: Hospital wastewater is a major source of antimicrobial resistance (AMR) outflow into the environment. This study uses metagenomics to study how hospital clinical activity impacts antimicrobial resistance genes (ARGs) abundances in hospital wastewater. Methods: Sewage was collected over a 24-h period from multiple wastewater collection points (CPs) representing different specialties within a tertiary hospital site and simultaneously from community sewage works. High throughput shotgun sequencing was performed using Illumina HiSeq4000. ARG abundances were correlated to hospital antimicrobial usage (AMU), data on clinical activity and resistance prevalence in clinical isolates. Results: Microbiota and ARG composition varied between CPs and overall ARG abundance was higher in hospital wastewater than in community influent. ARG and microbiota compositions were correlated (Procrustes analysis, p=0.014). Total antimicrobial usage was not associated with higher ARG abundance in wastewater. However, there was a small positive association between resistance genes and antimicrobial usage matched to ARG phenotype (IRR 1.11, CI 1.06-1.16, p<0.001). Furthermore, analyzing carbapenem and vancomycin resistance separately indicated that counts of ARGs to these antimicrobials were positively associated with their increased usage [carbapenem rate ratio (RR) 1.91, 95% CI 1.01-3.72, p=0.07, and vancomycin RR 10.25, CI 2.32-49.10, p<0.01]. Overall, ARG abundance within hospital wastewater did not reflect resistance patterns in clinical isolates from concurrent hospital inpatients. However, for clinical isolates of the family Enterococcaceae and Staphylococcaceae, there was a positive relationship with wastewater ARG abundance [odds ratio (OR) 1.62, CI 1.33-2.00, p<0.001, and OR 1.65, CI 1.21-2.30, p=0.006 respectively]. Conclusion: We found that the relationship between hospital wastewater ARGs and antimicrobial usage or clinical isolate resistance varies by specific antimicrobial and bacterial family studied. One explanation, we consider is that relationships observed from multiple departments within a single hospital site will be detectable only for ARGs against parenteral antimicrobials uniquely used in the hospital setting. Our work highlights that using metagenomics to identify the full range of ARGs in hospital wastewater is a useful surveillance tool to monitor hospital ARG carriage and outflow and guide environmental policy on AMR.