Kern et al site of the frontal, maxillary, and anterior ethmoid sinuses (Witterick and Kolenda 2004), which often plays a role in perpetuation of the disease (Slavin et al 2005). Although studies have shown positive outcomes from surgery, with subjective improvement ranging from 70% to 98% of patients, surgery does not necessarily cure the disease and should be considered as an adjunct to medical therapy. Medical treatment is often still required after surgery, but possibly less frequently (Witterick and Kolenda 2004). With current evidence pointing to the fungal etiology of CRS, there has been a trend towards treatment of CRS with topical antifungal medication, namely Amphotericin B (AmB). AmB is a natural polyene antifungal that is not absorbed through the gastrointestinal tract. AmB binds to ergosterol, a component of cell walls of most fungi, leading to formation of ion channels and cell death; AmB may also act secondarily through oxidative damage to fungal cell membranes through creation of free radicals from its own oxidation (Groll et al 2003). It is hypothesized that topical intranasal application of AmB can decrease the fungal load in the sinonasal region, thereby decreasing the local eosinophilic inflammatory reaction to fungal antigens seen in many CRS patients (Ponikau, Sherris, Weaver, et al 2005). The toxicity of intravenously administered AmB has been well characterized at much higher concentrations than are administered intranasally. There is clear evidence that AmB is poorly absorbed through the gut when ingested orally, therefore there is little or no potential for systemic exposure to the drug when administered by the topical intranasal route (Wise et al 1982; AmB PI 1996). Although topical intranasal AmB has been considered by some as a controversial therapy, there is increasing evidence for the efficacy and safety of this antifungal drug for CRS patients. In a 2002 pilot study, 75% of CRS patients had improvement of symptoms, and 75% showed improvement on endoscopic exam (Ponikau et al 2002). In a study of 74 patients with persistent nasal polyposis despite saline lavage and corticosteroid spray, addition of intranasal AmB was associated with complete disappearance of polyps in 39% of patients (Ricchetti et al 2002). A randomized controlled study of CRS patients with polyposis showed no improvement on CT and slightly worse symptom scores for AmB patients (Weschta et al 2004). However, this study excluded anyone with a clinical suspicion of AFRS based on the Brent-Kuhn criteria (Weschta et al 2004), the diagnostic criteria proposed for AFRS. In the original Brunt-Kuhn criteria for allergic fungal sinusitis (AFS), one needed positive allergy testing, the 324 presence of fungi on histology or culture, eosinophilic “allergic mucin”, and the presence of positive evidence on CT scan with nasal polyps. In the evidence based on our studies, CRS does not require positive allergy testing (ie, less than 50% of our patients had immunologic evidence of allergy). These criteria have been demonstrated to be present in the majority of CRS patients, placing the AFRS subentity into question (Ponikau et al 1999). More recently, a randomized controlled trial was conducted with 30 CRS patients. This study demonstrated improvement in CRS on CT scan in the AmB group at 6 months, with a mean decrease in mucosal thickening of 8.8% compared with a mean increase of 2.3% for the placebo group (p=0.03). In addition, 70% of the AmB patients had improved endoscopy scores, and 9 out of 10 AmB patients had improvement of symptoms as measured by SNOT-20 (compared with 6 of 14 placebo patients). The only adverse event due to AmB was the feeling of burning at the time of administration in 2 patients (Ponikau, Sherris, Weaver, et al 2005). The majority of these studies suggest that AmB is an effective means of decreasing mucosal inflammation and improving symptoms in CRS patients. This positive effect occurs, in all likelihood, by decreasing the fungal antigen load, which in turn “shuts off” the eosinophilic response. It appears that the initiation of the immunologic response is the result of new hyphae, new spores, and this takes time for the reaction to be modulated and reduced. If there are antigenic portions of the fungi still present, it would initiate the continuation of the immunologic response. Destroying the fungi and reducing the amount of new hyphae and spores in turn reduces the immunologic response of the body in sensitized individuals. Therefore, this reduces the degranulation of eosinophils and reduces the eosinophilic population. Usually this reaction stops within a three month period. Conclusion AmB is safe and generally well tolerated by patients because is a topical therapy with minimal absorption. AmB should therefore be considered as a first-line therapy in CRS prior to considering surgical intervention. In patients with severe and extensive nasal polyps, it is best to operate and surgically remove the polyps and the mucus with its toxic MBP. Surgical removal of obstructing polypoid disease allows post-surgical access for the use of topical intranasal AmB to prevent and minimize disease recurrence. The endoscopic surgery to remove polyps with antrostomy allows AmB to Therapeutics and Clinical Risk Management 2007:3(2)