Application of Combined Genomic and Transfer Analyses to Identify Factors Mediating Regional Spread of Antibiotic Resistant Bacterial Lineages

Background: Patients entering nursing facilities (NFs) are frequently colonized with antibiotic resistant organisms (AROs). To understand the determinants of ARO colonization on NF admission we applied whole-genome sequencing to track the spread of four ARO species across regional NFs and evaluated patient-level characteristics and transfer acute-care hospitals (ACHs) as risk factors for colonization.

Methods: 584 patients from six NFs were surveyed for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecalis/faecium (VREfc/VREfm) and ciprofloxacin-resistant Escherichia coli (CipREc) colonization. Genomic analysis was performed to quantify ARO spread between NFs and compared to patient-transfer networks. The association between admission colonization and patient-level variables and recent ACH exposures was examined using multivariable regression models.

Results: The majority of ARO isolates across study sites belonged to major healthcare-associated lineages: MRSA (ST5;N=89/117); VREfc (ST6;N=68/75); CipREc (ST131;N=58/64), and VREfm (clade A;N=129/129). While the genomic similarity of strains between NF pairs was associated with overlap in their feeder ACHs (Spearman's rho=0.44-0.75, p<0.05 for MRSA, VREfc and CipREc), limited phylogenetic clustering by either ACH or NF supported regional endemicity. Significant predictors for ARO colonization on NF admission included lower functional status (adjusted odds ratio [aOR]>1 for all four AROs) and recent exposure to glycopeptides (aOR>2 for VREfm, VREfc and MRSA) or 3rd/4th-generation cephalosporins (aOR>2 for MRSA and VREfm). Transfer from specific ACHs was an independent risk factor for only one ARO/ACH pair (VREfm/ACH19, aOR=2.48[1.06-5.83]).

Conclusion: In this region, healthcare-associated ARO lineages are endemic among connected NFs and ACHs, making patient characteristics more informative of NF admission colonization risk than exposure to specific ACHs.

This repository contains genomic datasets, example clinical data, and analysis scripts for generating figures in the manuscript published in Clinical Infectious Diseases in 2020.

Genomic sequences are available from BioProject PRJNA435617.