N-acetylcysteine (NAC) is an antioxidant commonly used in the treatment of acetaminophen overdose, and has well documented mucolytic properties. In vitro, NAC has been shown to significantly inhibit the formation of bacterial biofilms when used alone or enhance the antimicrobial effects of other drugs such as ciprofloxacin (3), fosfomycin and tigecycline when used in combination (4-6). The application of NAC to the middle ear in patients with tympanostomy tubes has been shown to increase tube longevity, and decrease the replacement of tubes, recurrence of infection, tympanosclerosis, and subsequent physician visits (7). Recent findings from a case series suggest that the addition of N-acetylcysteine (NAC) to Ciprodex otic solution is a superior treatment for chronic otitis media compared to Ciprodex alone (3). Although the practice of supplementing Ciprodex otic solution, a standard pharmacologic treatment for otitis media, with NAC in order to treat patients with difficult infections holds therapeutic promise, the efficacy of the treatment has not been objectively assessed in a controlled study to date in a patient population of adequate size.