Advancements in comparative genomics have generated significant interest in defining applications for health care-associated pathogens. Clinical microbiology, however, relies on increasingly automated platforms to quickly identify pathogens, resistance mechanisms, and therapy options within Clinical Laboratory Improvement Amendments (CLIA)- and FDA-approved frameworks. Additionally, and most notably, health care-associated pathogens, especially those that are resistant to antibiotics, represent a diverse spectrum of genera harboring complex genetic targets, including antibiotic, biocide, and virulence determinants that can be highly transmissible and, at least for antibiotic resistance, serve as potential targets for containment efforts. U.S. public health investments have focused on rapidly detecting outbreaks and emerging resistance in health care-associated pathogens using reference, culture-based, and molecular methods that are distributed, for example, across national laboratory network infrastructures. Herein we describe the public health applications of genomic science that are built from the top-down for broad surveillance, as well as the bottom-up, starting with identification of infections and infectious clusters. For health care-associated, including antimicrobial-resistant, pathogens, we propose a combination of top-down and bottom-up genomic approaches leveraged across the public health spectrum, from local infection control, to regional and national containment efforts, to national surveillance for understanding emerging strain ecology and fitness of health care pathogens.
