Strain sharing and persistence of microbial pathogens colonizing the skin of residents in a regional nursing home network.

Antimicrobial resistance (AMR) is a global public health threat that disproportionately affects vulnerable populations, including nursing home (NH) residents. Surveillance and control in NHs are resource-limited and typically restricted to perirectal cultures, overlooking both skin colonization and multidrug-resistant organisms (MDROs) not recovered by selective media. Here we show, within the cluster-randomized Project PROTECT trial ( NCT03118232 ), that residents' skin serves as a major reservoir of transmissible MDROs. We analyzed 207 groin and axilla swabs from 38 residents across 15 California NHs using shotgun metagenomics, selective culturing, and isolate genome sequencing. Culture detected MDROs in 10 of 38 residents (26.3%), including extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli ST131/ST648 in 4 (10.5%) and methicillin-resistant Staphylococcus aureus in 7 (18.4%). In contrast, metagenome-assembled genomes identified broader MDRO colonization, including multidrug-resistant E. coli ST93 in 27 residents (71.1%), methicillin-resistant Staphylococcus epidermidis ST2 in 14 (36.8%), Proteus mirabilis in 16 (42.1%), Providencia stuartii in 7 (18.4%), Enterococcus faecalis in 7 (18.4%), and Pseudomonas aeruginosa in 5 (13.2%). Colonization persisted after bathing. Clonal E. coli ST93 (<=30 SNPs) was shared by 27 residents across 9 facilities, and 5 resident pairs (13.2%) carried clonally related strains of >=2 MDRO species, consistent with polymicrobial transmission. Our findings demonstrated the skin as a persistent reservoir of MDROs and the importance of metagenomic surveillance to uncover hidden colonization and transmission pathways, underscoring the need to expand AMR monitoring in long-term care.