Response to letter to the editor

Abstract

We greatly appreciate the interest and report of Drs Myoken, Sugata, Fujita, Kohara, and Mikami as summarized in their Letter to the Editor. Their letter reviews a prior study where high rates of colonization of the oropharynx by Candida species were seen in HCT patients, despite systemic and topical prophylaxis.1Epstein J.B. Hancock P.J. Nantel S. Oral candidiasis in hematopoietic cell transplantation patients An outcome-based analyis.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003; 96: 154-163Google Scholar This prior report is consistent with the data they present in their letter. In their study of 22 patients, they found mucositis in all patients, and reported the use of oral itraconazole and oral rinsing with amphotericin B suspension. Colonization was seen in half of their patients, but clinical infection was not seen. These findings are consistent with the prior report.1Epstein J.B. Hancock P.J. Nantel S. Oral candidiasis in hematopoietic cell transplantation patients An outcome-based analyis.Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2003; 96: 154-163Google Scholar We have conducted a phase IV trial at the University of Washington (Epstein JB, Truelove EL, Hanson-Huggins K, Manel LA, Chen A, Press OW, Petersdorf SH, Fritsche TR, Epstein JD) to assess the effectiveness of amphotericin B oral suspension versus nystatin oral suspension in the prevention of oral colonization by Candida species in hematopoietic cell transplant (HCT) patients (data unpublished). Forty patients provided systemic fluconazole for prophylaxis were randomized to receive amphotericin B oral suspension or nystatin oral suspension four times daily, beginning prior to autologous stem cell infusion and continuing to Day +21, discharge from hospital or withdrawal from the study. Oral examinations and cultures were conducted twice weekly and adverse events and compliance were recorded. Cultures were taken for quantitative counts and species identification using standard techniques. Ulcerative mucositis occurred in 84.6% and no differences were seen in patients with Candida and the severity of mucositis. Systemic and topical antifungal treatment resulted in a decrease in the number of colonized patients (54.8% before treatment; 23.1% during treatment); however, oral colonization was not eliminated. Tolerability of the oral rinses was limited, with greater non-compliance in the amphotericin B than the nystatin group. When either topical was discontinued, colony counts of Candida species increased despite continuing systemic fluconazole. Reports of altered taste appeared to be greater in the amphotericin B group. These results suggest that topical anti-fungal rinses further control oropharyngeal colonization by Candida species in patients on systemic anti-fungals receiving HCT, but the benefit is limited by tolerability of the oral rinses. The results in our recent unpublished trial confirm the prior study and the findings reported in the letter to the editor that show that oropharyngeal colonization by Candida species is not eliminated by topical and systemic therapy, although clinical infection may be reduced. Randomized controlled studies with larger patient numbers and longer term studies are indicated, which should include assessment of Candida species in the oropharynx, outcomes including systemic infection, and assessment of Candida resistance following topical and systemic therapy. The spectrum of itraconazole may make this a desirable agent for systemic prophylaxis in these patients, but comparative and longer term trials are needed, as described by Dr. Myoken. Topical agents appear to further control oropharyngeal colonization, however, because compliance with topical polyenes is limited in HCT patients, new formulations of topical antifungals should be considered. Oropharyngeal candidiasis and systemic candidiasis and systemic candidiasis remain of considerable concern for patients receiving aggressive neutropenia-inducing chemotherapy, and HCT and continuing research is necessary.