Defining high-risk genomic groups of Stenotrophomonas maltophilia

About This Grant

ABSTRACT Stenotrophomonas maltophilia is an environmental, aerobic, non-fermentative Gram-negative bacterium that is increasingly recognized as an important cause of healthcare-associated infections. It is intrinsically resistant to most β-lactam agents including carbapenems that are the last-resort, broad-spectrum agents for difficult-to-treat bacterial infections and is now among the most frequently isolated carbapenem-resistant Gram-negative bacteria. S. maltophilia has generally been perceived as a low virulence pathogen that colonizes the respiratory tract of acutely or chronically ill patients. At the same time, some patients develop serious infections such as bacteremia or pneumonia due to S. maltophilia and do not survive them. This dichotomy may be partially explained by host factors including underlying medical conditions and acuity of illness at the time of infection; however, much less is known about strain factors of S. maltophilia that may impact clinical presentation and patient outcomes. In a recent, prospective, multicenter clinical/genomic cohort study of S. maltophilia conducted at hospitals in Japan, all strains belonged to the genus Stenotrophomonas by whole genome sequencing, but only a third were identified as S. maltophilia sensu stricto. Other strains belonged to various Stenotrophomonas genomic groups that were spread across the hospitals. We observed several genomic groups associated with high infection rates, including S. pavanii, S. muris, S. maltophilia genomic group 7 and a distinct genomic subgroup of S. maltophilia. These potential high-risk genomic groups were also more commonly associated with bloodstream infection and higher 30-day mortality rates. These findings led us to hypothesize that S. maltophilia consists of diverse genomic groups including previously unrecognized groups, and that specific genomic groups within the S. maltophilia complex are more likely to cause infections and adverse patient outcomes than others. In this project, by leveraging an established network of US hospitals for studying drug-resistant pathogens and infections, we will prospectively collect the demographic, clinical and microbiological data of patients with a S. maltophilia clinical culture at six large hospital systems to facilitate rigorous discrimination of infection or colonization, and determination of clinical outcome, with the goal of linking genomic groups with infection and outcomes, and characterizing phenotypic features of each genomic group. We will then compare virulence in in vivo infection models and develop a PCR assay to rapidly identify major genomic groups. The ability to predict the risk of adverse clinical outcomes based on specific genomic group has the potential to transform the approach to patients at risk of S. maltophilia complex infection and optimize their management.