Candida glabrata colonization is common in patients receiving radiation treatment for head and neck cancer, but to our knowledge has never been described as the infecting organism with oropharyngeal candidiasis (OPC). This study presents the first three patients described with C. glabrata OPC in this patient population. Patient 1 developed C. glabrata OPC and required fluconazole, 800 mg/day, for clinical resolution. Antifungal susceptibility testing revealed a MIC of fluconazole of >64 g/ml. Elapsed time from initial culturing to treatment decision was 7 days. Patients 2 and 3 developed C. glabrata OPC. They were patients in a study evaluating OPC infections, and cultures were taken immediately. CHROMagar Candida plates with 0, 8, and 16 g of fluconazole/ml were employed for these cultures. Lavender colonies, consistent with C. glabrata, grew on the 0-and 8-g plates but not on the 16-g plate from patient 2 and grew on all three plates from patient 3. Based on these data, a fluconazole dose of 200 mg/day was chosen for patient 2 and a dose of 400 mg/day was chosen for patient 3, with clinical resolution in both. Elapsed time from initial culturing to treatment decision was 2 days. C. glabrata does cause OPC in head and neck radiation treatment patients, and the use of fluconazole-impregnated chromogenic agar may significantly reduce treatment decision time compared to that with conventional culturing and antifungal susceptibility testing. CASE REPORTS Patient 1. Patient 1 was a 47-year-old white male diagnosed with squamous cell carcinoma of the base of the tongue, stage T2N2M0. He was treated with a combination of 7,200 cGy of radiation over 8 weeks and concomitant cisplatin and 5-fluorouracil chemotherapy during weeks 1 and 5. During the fifth week of his treatment he developed oropharyngeal candidiasis (OPC) and was placed on fluconazole, 100 mg/day, with initial resolution. After 2 weeks the candidiasis recurred, and the fluconazole dose was raised to 200 mg/day. The OPC did not resolve, and so the fluconazole dose was raised to 400 mg/day, and a swab culture of lesions was taken. The OPC continued. The culture was plated on blood agar, and identification included germ tube evaluation and API-20C confirmation (bioMerieux, Marcy-l'Etoile, France). The culture grew Candida glabrata, and antifungal susceptibility testing was performed according to NCCLS-recommended techniques (1). The 48-h MIC of fluconazole was 64 g/ml. The patient's fluconazole dose was raised to 800 mg/day with clinical resolution of OPC. The total elapsed time for culture and antifungal susceptibility results was 7 days.Patients 2 and 3. Patients 2 and 3 were participating in a clinical study where they had cultures taken every week during their radiation treatment. With these patients, cultures employed an oral swab and a swish sample of 10 ml of normal saline instilled in the mouth for 10 s and then collected in a sterile container. These samples were plated on blood agar, RPMI medium, and CHROMagar Candida (CHROMagar Company, Paris, Fran...

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Merkel cell carcinoma (MCC) is an uncommon but malignant cutaneous neuroendocrine carcinoma with a high incidence of local recurrence, regional lymph node metastases, and subsequent distant metastases. The etiology of MCC remains unknown. It usually occurs in sun-exposed areas in elderly people, many of whom have a history of other synchronous or metachronous sun-associated skin lesions. The outcome for most patients with MCC is generally poor. Surgery is the mainstay of treatment. The role of adjuvant therapy has been debated. However, data from recent development support a multimodality approach, including surgical excision of primary tumor with adequate margins and sentinel lymph node dissection followed by postoperative radiotherapy in most cases, as current choice of practice with better locoregional control and disease-free survival. Patients with regional nodal involvement or advanced disease should undergo nodal dissection followed by adjuvant radiotherapy and, perhaps, systemic platinum-based chemotherapy in most cases.

Candida glabrata has emerged in recent years as a significant cause of systemic fungal infection. We have previously reported on the first three patients receiving radiation for head and neck cancer to develop oropharyngeal candidiasis due to C. glabrata. The goal of this study was to track the development of increased fluconazole resistance in C. glabrata isolates and to evaluate previously described genetic mechanisms associated with this resistance from one of these three patients. The patient was a 52-year-old man with squamous cell carcinoma treated with radiation. At week 7 of his radiation, he developed oropharyngeal candidiasis, which was treated with 200 mg of fluconazole daily for 2 weeks. Serial cultures from this and three subsequent time points yielded C. glabrata. Isolates from these cultures were subjected to antifungal susceptibility testing, DNA karyotyping, and evaluation of the expression of genes previously associated with C. glabrata resistance to fluconazole, CgCDR1, CgCDR2, and CgERG11. Two strains (A and B) of C. glabrata were identified and found to display different patterns of resistance development and gene expression. Strain A developed resistance over a 2-week period and showed no overexpression of these genes. In contrast, strain B first showed resistance 6 weeks after fluconazole therapy was discontinued but showed overexpression of all three genes. In conclusion, development of resistance to fluconazole by C. glabrata is a highly varied process involving multiple molecular mechanisms.