AbstractThe value of topical administration of antimicrobial agents to prevent irradiation mucositis of the oral cavity and oropharynx was investigated in this pilot study. Thirty‐six patients receiving radiotherapy for head and neck cancer were included. Lozenges containing polymyxin E, tobramycin, and amphotericin B (PTA‐lozenges) were administered during and after the course of irradiation to eradicate gram‐negative bacilli and yeasts. Mucosal reactions and dysphagia were assessed and oropharyngeal cultures were obtained. Thirty‐six patients treated in a previous period served as controls. Sixteen of the 36 patients in each group received irradiation predominantly to the oral mucosa. Confluent mucositis was observed in only 1 of 16 patients receiving PTA‐lozenges but in 10 of the 16 patients of the control group (P = 0.001). Average duration of mucositis was also less with PTA‐lozenges as well as dysphagia. Mucosal reactions and dysphagia in the patients who had mainly oropharyngeal mucosa in the treatment volume were not reduced. Persistent colonization by gram‐negative bacilli occurred in only three patients. It is concluded that topical administration of polymyxin E, tobramycin, and amphotericin B may reduce irradiation mucositis of the oral cavity. The underlying mechanism must be further elucidated. © 1995 Wiley‐Liss, Inc.