Preclinical Rat Models of Infectious Otitis Media Induced by Staphylococcus aureus and Pseudomonas aeruginosa: A Systematic Review

Otitis media remains a common infectious condition and continues to pose therapeutic challenges, particularly in cases involving bacterial pathogens with increasing antimicrobial resistance. Preclinical animal models are essential for understanding disease mechanisms and for evaluating candidate therapies prior to clinical translation. Among available experimental systems, rat models offer anatomical and immunological features that are suitable for studying middle ear infections. This systematic review aims to comprehensively identify and critically appraise experimental studies that employed rat models of infectious otitis media induced by Staphylococcus aureus and Pseudomonas aeruginosa. The review will focus on methodological aspects of model induction, including bacterial strains, inoculation routes, bacterial dose, duration of infection, and confirmation methods. In addition, outcome measures related to histopathology, inflammatory response, microbiological findings, and therapeutic interventions will be summarized. The review will be conducted in accordance with PRISMA guidelines for systematic reviews and will incorporate preclinical-specific quality assessment using the SYRCLE risk of bias tool and relevant ARRIVE recommendations. Electronic searches will be performed across major biomedical databases. Eligible studies will include original experimental research using rats, while reviews, meta-analyses, and non-animal studies will be excluded. By synthesizing existing evidence on rat models of Staphylococcus aureus– and Pseudomonas aeruginosa–induced otitis media, this review is expected to inform the design of robust and reproducible preclinical models and to support the development of future therapeutic studies.