Deciphering Stenotrophomonas: Mechanistic Insights for Malignancy-Related Infections

Abstract Stenotrophomonas maltophilia, a multidrug-resistant global health threat, particularly affects hematologic malignancy patients, leading to rapid fatal outcomes. The prompt and effective treatment of S. maltophilia infections is critically hindered by outdated or absent pharmacokinetic data, unreliable susceptibility tests, and outdated or nonexistent clinical breakpoints. Our Central Hypothesis is that rationally optimized antibiotic dosing will achieve extensive killing and prevent resistance emergence against S. maltophilia isolates. Preliminary studies provide compelling evidence to support our initiative. In Aim 1, in vitro models will assess optimized antibiotic dosing by profiling bacterial killing and resistance suppression. Aim 2 involves multi-omic and exposure-response evaluations of pre- and post-exposure isolates, guiding translation to understand failed dosing strategies. The project aims to validate dosing strategies for future trials targeting S. maltophilia.