Antimicrobial resistance (AMR) is a global threat. A better understanding of how antibiotic use and between-ward patient transfers (or connectivity) impact population-level AMR in hospital networks can help optimize antibiotic stewardship and infection control strategies. Here, we used a metapopulation framework to explain variations in the incidence of infections caused by 7 major bacterial species and their drug-resistant variants in a network of 357 hospital wards. We found that ward-level antibiotic consumption volume had a stronger influence on the incidence of the more resistant pathogens, while connectivity had the most influence on hospital-endemic species and carbapenem-resistant pathogens. Piperacillin-tazobactam consumption was the strongest predictor of the cumulative incidence of infections resistant to empirical sepsis therapy. Our data provide evidence that both antibiotic use and connectivity measurably influence hospital AMR. Finally, we provide a ranking of key antibiotics by their estimated population-level impact on AMR that might help inform antimicrobial stewardship strategies.

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Antimicrobial resistance (AMR) is a global threat. A better understanding of how antibiotic use and betweenward patient transfers (or connectivity) impact hospital AMR can help optimize antibiotic stewardship and infection control strategies. Here, we used metapopulation ecology to explain variations in infection incidences of 17 ESKAPE pathogen variants in a network of 357 hospital wards. Multivariate models identified the strongest influence of ward-level antibiotic use on more resistant variants, and of connectivity on nosocomial species and carbapenem-resistant variants. Pairwise associations between infection incidence and the consumption of specific antibiotics were significantly stronger when such associations represented a priori AMR selection, suggesting that AMR evolves within the network. Piperacillin-tazobactam consumption was the strongest predictor of the cumulative incidence of infections resistant to empirical sepsis therapy. Our data establish that both antibiotic use and connectivity measurably influence hospital AMR and provide a ranking of key antibiotics by their impact on AMR.