N-Acetylcysteine as an Adjunct for Refractory Chronic Suppurative Otitis Media

Chronic suppurative otitis media (CSOM) is the presence of symptoms, signs, and physical findings that can result in long-term damage to the middle ear as a result of infection or inflammation. The condition is defined as chronic drainage from the ear, lasting longer than 12 weeks, through a perforated tympanic membrane. Although the pathogenesis may result from the actions of inflammatory mediators and cytokines released following an infection, recent evidence also suggests that biofilm formation may be responsible for sustaining the inflammatory response that promotes the persistent effusion (1). These patients present a challenge to otolaryngologists because a number do not respond to typical oral and topical antibiotics.

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.

The purpose of this study will be to assess the efficacy of Ciprodex augmented with NAC compared to Ciprodex alone in a blinded study in subjects for whom other therapies for a chronically draining ear have been ineffective.

Hypothesis:

The cessation of otorrhea is expected to be achieved in a greater number of subjects with otorrhea treated with Ciprodex otic solution supplemented with NAC compared to Ciprodex alone. We expect that patients treated with Ciprodex augmented with NAC will experience an earlier cessation of symptoms and a longer duration of complete response following treatment.