Antibiofilm and Quorum-sensing Agents Against Pseudomonas aeruginosa and Staphylococcus aureus: a Systematic Review of Preclinical Studies, 2022-2026

Background: Biofilm formation and quorum sensing (QS) make Pseudomonas aeruginosa and Staphylococcus aureus hard to treat, and many preclinical agents are reported to act against both. Objective: We mapped preclinical antibiofilm and anti-QS agents against these pathogens and graded how directly each study tested QS. Methods: PubMed and Scopus were searched without a date limit (3,349 records). Eligible in vitro and in vivo studies were published from 2022 onward, tested an exogenous agent and named either organism in the title. Full-text data were extracted, each study received a QS evidence tier, and risk of bias was appraised with an adapted checklist (in vitro) or SYRCLE's tool (vertebrate studies); two reviewers verified the extraction. Results: We included 252 studies, led by natural products (115). A QS assay in the target pathogen was present in 140 studies (56%), a surrogate reporter alone in 27 (11%), and 31 (12%) used a vertebrate infection model. In vitro risk of bias was low in 143, moderate in 93 and high in 16. No meta-analysis was done, and title-only organism matching may have missed studies. Conclusion: Direct QS evidence is common for P. aeruginosa but thinner for S. aureus, and animal and cytotoxicity data are sparse.