br Discussion Serious infections caused by S apiospermum hav

Discussion Serious infections caused by S. apiospermum have been increasingly reported in recent years. The sexual phase of S. apiospermum is Pseudallescheria apiosperma. Its occurrence is promoted in manure-enriched or polluted environments, such as agricultural land, garden soil, sewer or ditch mud, and polluted pond bottoms. Serious infection is more common in temperate climates and less frequently encountered in the tropics.S. apiospermum causes a wide spectrum of conditions, including mycetoma, colonization of the airways, sinopulmonary infections, extrapulmonary localized infections, and disseminated infections. The term “mycetoma” represents a chronic, progressive, indolent mycosis characterized by tumefaction (subcutaneous tissues become edematous), multiple draining sinuses, and extrusion of grains. Mycetoma can be caused by soil-inhabiting bacteria (actinomycosis) or fungi (eumycetoma). In one retrospective study of 63 cases in the United States, S. apiospermum is the most common fungal etiologic agent of mycetoma. Histopathologically, mycetoma shows nodular Bleomycin Sulfate of fungal hyphae, which are more easily demonstrated by PAS or GMS stains. In tissue sections, S. apiospermum displays septate and branched hyphae, and can be mistaken as Aspergillus, Fusarium, or other species of black fungi. Kimura et al found that the combination of haphazardly branching hyphae and lemon-shaped conidia was the most useful feature to differentiate S. apiospermum from other filamentous fungi in tissue. Diagnosis of S. apiospermum infection is confirmed by culture of the infected tissue. The colony typically looks light to brownish gray with a mouse fur-like appearance in 1–2 weeks, but other morphologically similar species can make the identification of S. apiospermum difficult. In the present study, we applied PCR to amplify the ITS1, ITS2, and D1–D2 regions of 26S rDNA. The amplicons were sequenced and the resulting sequences were used for searching homologous sequences in public databases using the BLASTN algorithm (http://www.ncbi.nlm.nih.gov.eleen.top/BLAST/). The BLAST search hit best-scoring sequences from S. apiospermum with 99.4% (ITS1), 100% (ITS2), and 99.0% (D1–D2) similarities. Treatments of mycetomatous S. apiospermum infection include surgical debridement and antifungal therapy. The former should be applied if the lesion is localized. Antifungal therapy is considered as a conservative treatment for those who are too weak to have surgery or as an adjuvant treatment to surgery for refractory mycetoma. S. apiospermum has very high levels of resistance to conventional antifungal drugs. Among azoles tested for in vitro activity against S. apiospermum, voriconazole has the most potent effect (MIC50, 0.25 μg/mL), followed by miconazole (MIC50, 0.5 μg/mL), and albaconazole (MIC50, 0.5–1 μg/mL). On the contrary, itraconazole (MIC50, 4.5 μg/mL), ketoconazole (MIC50, 10.07 μg/mL), and amphotericin B (MIC50, 4 μg/mL) showed poor antifungal activity. Voriconazole is a broad-spectrum azole antifungal agent and can be administered intravenously and orally with excellent bioavailability. In a large series of 107 patients with scedosporiosis treated with voriconazole (6 mg/kg of body weight intravenously twice daily on Day 1, followed by 4 mg/kg intravenously twice daily and then switching to oral therapy at 200 mg twice daily), a successful therapeutic response was achieved in 57% of patients (median, 103 therapy days), with >98% of patients responding after receiving >28 days of therapy. The best therapeutic responses were seen for skin/subcutaneous (91%) or bone (79%) infections, and the lowest for central nervous system infections (43%). Thereafter, sporadic cases with cutaneous S. apiospermum infections successfully treated by oral or intralesional voriconazole have also been reported. Although voriconazole is active against a broad range of fungal pathogens, several adverse events have been described, including reversible visual disturbances, hallucinations, abdominal pain, and hepatitis, allergic skin reactions, and, less frequently, lymphadenopathy or pancytopenia. Our patient had a transient elevation of liver function tests after 3 months of voriconazole administration, which recovered after the use of voriconazole was held for 1 week.