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absorption, lower costs, and decreased morbidity. Solares and colleagues (51) have shown encouraging data supporting the use of topical mupirocin nasal irrigations as an alternative to intravenous antibiotics in the treatment of acute exacerbations of CRS due to MRSA. Patients using mupirocin in sinus irrigations showed improved symptoms and reduced MRSA recovery on subsequent cultures. A more recent study found that twice-a-day nasal irrigation with 0.05% mupirocin in Ringer solution improved endoscopic findings in 93% of patients, whereas 75% had symptom improvement (52). For MRSA rhinosinusitis, topical antibiotic therapy with mupirocin appears to be both safe and effective, and may replace oral and intravenous treatments in some patients. In theory, patients who have had sinus surgery with large antrostomies should be better candidates for widespread delivery of topical antimicrobials than nonsurgical patients. Grobler and coworkers (53) found that 3.95 mm was the minimum ostium diameter to guarantee penetration of topical therapies into the maxillary sinus. A study by Kobayashi and Baba (54) demonstrated that nonsurgical patients did not achieve sufficient concentrations of topical antibiotics in the maxillary sinus after irrigation. However, in a review of topical antimicrobials for chronic sinusitis, Lim and colleagues (55) found that topical therapies were effective for both surgical and nonsurgical patients, but with higher levels of evidence for postsurgical patients. Macrolide Therapy for CRS The use of long-term macrolide therapy originated in Japan, where it reduced the mortality rate of diffuse panbronchiolitis and concomitantly improved sinus symptoms (56). Use of erythromycin in the treatment of diffuse panbronchiolitis was eventually attributed to the drug’s antiinflammatory and immunomodulatory effects. Macrolides have been found to inhibit inflammatory mediators such as IL-1B, IL-8, and intercellular adhesion molecule-1 (57). Other effects include protecting bioactive phospholipids, reducing the number of neutrophils by accelerated apoptosis, and increasing mucociliary transport (6). In a double-blind, randomized, placebo-controlled clinical trial of low-dose roxithromycin or placebo for 3 months in 64 subjects with CRS, there was a statistically significant improvement in the SNOT-20 score, nasal endoscopy examination, Figure 2. Electron micrograph demonstrating mixed fungal and Pseudomonas biofilm. *Indicates Pseudomonas; 5 indicates fungus. Photo courtesy of Noam Cohen, M.D., Ph.D. Suh and Kennedy: Treatment Options for Chronic Rhinosinusitis 135 saccharine transit time, and IL-8 levels in lavage fluid in the macrolide group. In another study, erythromycin or clarithromycin was given to patients with chronic rhinosinusitis with nasal polyps. After 3 months, the IL-8 levels were significantly decreased, which corresponded to a decrease in size of the nasal polyps (58). Available evidence suggests that low-dose, long-duration macrolide therapy is safe and can result in improvements in both subjective and objective measures of CRS in select patients. ANTIFUNGAL THERAPY FOR CRS Background There has been considerable controversy in the literature regarding the role of fungus in the etiology of CRS. Ponikau and coworkers (59) hypothesized that fungal colonization is an important stimulus for persistent inflammation in patients with CRS, including those with or without nasal polyps. The group isolated fungal organisms in 96% of patients with CRS. However, in the same study, 100% of healthy control subjects also had positive fungal cultures. It has also been found that immune cells from patients with CRS react to
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