Systematic review of prophylactic antibacterial agents for radiation-induced oral mucositis in head and neck cancer.

OBJECTIVE: To examine the use of treatments with antibacterial properties as prophylaxis prior to radiotherapy (RT), either alone or in combination with chemotherapy (CT), to prevent and reduce radiation-induced oral mucositis (RIOM) in patients with head and neck cancer (HNC). DATA SOURCES: A systematic search following PRISMA guidelines was conducted across PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant studies published in English through March 2025. REVIEW METHODS: Eligible studies assessed prophylactic antibacterial interventions aimed at preventing RIOM. RESULTS: From 86 retrieved citations, 9 articles met inclusion criteria. Antibacterial agents assessed included polymyxin, tobramycin, amphotericin (PTA), povidone iodine, SAMITAL, and Nigella sativa (NS). Evidence supporting povidone iodine, PTA, and SAMITAL was inconclusive or failed to demonstrate statistically significant reductions in RIOM severity. Several studies reported discordant findings, with statistically significant improvements in patient-reported symptoms or quality-of-life measures despite nonsignificant clinician-assessed scores. NS demonstrated potential benefits in reducing RIOM incidence and severity compared with standard of care and other antibacterial agents. CONCLUSION: The systematic review highlights limited and inconsistent evidence supporting antibacterial prophylaxis for preventing and reducing RIOM severity in patients with HNC undergoing RT. Discrepancies between patient-reported outcomes and clinical-assessed grading suggest some treatments may provide symptomatic benefit not captured by traditional scoring systems. NS mouthwashes showed preliminary promise; however, evidence remains insufficient to establish superiority, and safety and regulatory concerns are persistent, particularly in immunosuppressed patients. Given the role of bacterial colonization and microbial dysbiosis in RIOM pathogenesis, larger, well-designed clinical trials with rigorous safety evaluations are warranted to investigate bacterial-directed preventive therapies.