Network of microbial and antibiotic interactions drive colonization and infection with multidrug-resistant organisms

Significance The proliferation of multidrug-resistant organisms (MDROs) is one of the world’s most pressing public health problems. Despite great efforts to prevent MDRO spread in healthcare facilities, antibiotic-resistant infections remain a significant threat. We hypothesized that current infection prevention initiatives are hindered by their targeting of individual MDROs; neglecting the fact that healthcare institutions have multiple circulating MDRO species whose propagation is driven by competing risk factors. We tested this hypothesis by identifying risk factors for the spread of multiple MDROs among nursing home residents and unraveled a complex network of interactions between antibiotic exposure and microbial factors. Our results indicate that interactions among MDROs and underlying drivers must be considered simultaneously to design optimal strategies to reduce MDRO propagation.