Abstract
BACKGROUND: Pseudomonas aeruginosa infective endocarditis (IE) presents a significant clinical challenge, leading to high rates of treatment failure and mortality. Even with the use of antipseudomonal β-lactams combined with aminoglycosides or fluoroquinolones, these therapies often fail to provide clinical resolution and are frequently accompanied by severe adverse effects. METHODS: We report a case of P. aeruginosa prosthetic valve endocarditis successfully treated with a combination of meropenem and ceftolozane/tazobactam. To investigate the synergistic effects of this combination, we conducted checkerboard, time-kill, human whole blood killing, and biofilm assays, as well as a simulated endocardial vegetation (SEV) model. RESULTS: Meropenem plus ceftolozane/tazobactam combination therapy successfully bridged the patient to cardiac surgery, achieving rapid microbiological clearance and sterile intraoperative valve cultures. While checkerboard assays showed additivity, time-kill assays with subtherapeutic antibiotic concentrations did not demonstrate synergy in standard media. However, significant synergy was observed in human whole blood and biofilm environments, with modestly improved activity in the SEV model. CONCLUSIONS: The combination of meropenem and ceftolozane/tazobactam demonstrates promising synergy in physiologically relevant conditions, offering a potentially safer alternative for treating P. aeruginosa IE and stabilizing complex patients prior to cardiac surgery. Further clinical investigation is needed to evaluate its efficacy and safety profile in severe Pseudomonas infections, including IE.