Fungal Theory Debated in Amphotericin B Controversy

Fenna Ebbens, MD, from the Academic Medical Center in Amsterdam, found in 2006 that treating 116 CRS patients with amphotericin B nasal lavage or placebo failed to show improvement in symptoms, nasal endoscopy scores, and other markers (J Allergy Clin Immunol 2006;118:1149-56). In a 2007 review article in Rhinology (45:178-89), she further stated that we conclude, on the basis of the results of our large, double-blind, placebo-controlled, multicenter study that direct topical administration of intranasal amphotericin B is not a solution for patients with CRS with or without nasal polyps, because neither major improvements nor significant differences between amphotericin B-treated and placebo-treated groups were observed.

Dr. Ebbens told ENT Today that amphotericin B remains a valuable antimycotic systemic treatment for potentially life-threatening invasive mycoses. Presently, in the absence of convincing evidence on clinical improvement of CRS upon therapy with both topical and oral antifungal agents, we should be careful about advocating widespread use of this drug. Widespread use may lead to resistance and, in time, we may lose a valuable antimycotic systemic drug, which still demonstrates low resistance.

Which brings the debate back to the Mayo results and advocates of amphotericin B. Jens Ponikau, MD, the physician-researcher who brought amphotericin B treatment to national attention when he was a graduate student, then a researcher at the Mayo Clinic, continues his work today as Clinical Assistant Professor of Otolaryngology at the University at Buffalo, State University of New York. In a number of studies and reviews (including US Respiratory Disease 2007, Touch Briefings; Therapeutics and Clinical Risk Management 2007;3:319-25; Clin Rev Allergy Immunol 2006;30:187-94), Dr. Ponikau has explained his findings in recent years, which include an identification of the specific antigen (the fungal agent Alternaria), the substance it secretes (eosinophilic major basic protein, eMBP), and the manner in which it binds to inflammatory cells.

The Devil Is in the Details

Regarding studies that have contradicted his findings, Dr. Ponikau told ENT Today that the devil is in the details. Although study results may vary, I think the difference is how the studies were conducted, he said.

Noting that both the Weschta and Ebbens studies excluded patients with fungal etiology, he compared this approach to testing an allergy medicine and excluding everybody who had allergies. Additionally, the Weschta trial included only patients with severe nasal polyposis. Dr. Ponikau said the drug was probably unable to reach the sinuses and the majority of the nasal cavity, due to blockage from the excessive polyps, specifically when a spray was used.