nnd-502 and Fusariosis

Fusariosis is the second most common mold infection after aspergillosis, and keratomycosis is the most encountered implantation infection. Here, we report a case of a 4-year-old Han Chinese girl presenting with an itchy mass on her right face of almost 2 years' duration. Direct smear of the lesion sample was positive for fungal hyphae. Biopsy of the lesion showed many fungal hyphae in the epidermis and dermis. The pathogen was identified as Fusarium lichenicola by molecular sequencing and phylogenetic analysis based on the TEF-1α gene. Whole-exome sequencing analysis using her peripheral blood revealed a heterozygous mutation in the STAT3 gene, which is related to autosomal dominant hyper-immunoglobulin E syndrome (AD-HIES). The lesion improved following treatment with i.v. and intralesional amphotericin B, oral voriconazole and topical luliconazole cream. To our knowledge, this is the second reported case of a special localized cutaneous lesion caused by Fusarium species in a child with AD-HIES. Both cases suggest that STAT3 deficiency may increase susceptibility to fusariosis.

Topics: Administration, Cutaneous; Administration, Oral; Amphotericin B; Antifungal Agents; Biopsy; Child, Preschool; DNA Mutational Analysis; Drug Therapy, Combination; Exome Sequencing; Face; Female; Fusariosis; Fusarium; Humans; Imidazoles; Injections, Intralesional; Job Syndrome; Skin; STAT3 Transcription Factor; Treatment Outcome; Voriconazole

Topics: Antifungal Agents; Fusariosis; Fusarium; Humans; Imidazoles; Microbial Sensitivity Tests

Fungal keratitis can be difficult to medically treat. Topical antifungals are usually applied empirically as the initial option in treating fungal keratitis. Natamycin (NAT) and/or voriconazole (VRCZ) have been widely used in the treatment of fungal keratitis. However, Fusarium solani species complex (FSSC), which are the dominant species of fungal keratitis, are resistant to VRCZ. This study investigated in vitro efficacy of luliconazole (LLCZ), a new imidazole antifungal, against FSSC and other filamentous fungi.. A total of 18 Fusarium isolates and 7 others were grown on potato dextrose agar at 30 and 37°C. For Fusarium, species identification and phylogenetic tree analysis were performed based on elongation factor-1α (EF-1α) DNA sequencing. The broth microdilution method was used for antifungal susceptibility testing of 11 antifungal drugs including LLCZ.. The 18 identified Fusarium isolates belonged to FSSC (n = 13), Fusarium oxysporum species complex (FOSC; n = 2), Fusarium chlamydosporum species complex (FCSC; n = 1), Fusarium incarnatum-equiseti species complex (FIESC; n = 1), and Fusarium fujikuroi species complex (FFSC; n = 1). We further divided 13 FSSC isolates into 3 clades, FSSC5 (n = 8), FSSC3 + 4 (n = 4), and FSSC9-a (n = 1), with 8 FSSC strains growing at 37°C. LLCZ showed lowest minimum inhibitory concentrations (MICs) against all tested filamentous fungi, with a MIC90 against the Fusarium species of 0.06 μg/mL, whereas MIC90 for NAT and VRCZ were 4 and 8 μg/mL, respectively.. LLCZ has the strongest in vitro antifungal activity among all drugs used against broad-range filamentous fungi including FSSC. LLCZ may potentially be a new medical treatment option for fungal keratitis.

Topics: Antifungal Agents; Eye Infections, Fungal; Fungi; Fusariosis; Fusarium; Humans; Imidazoles; Keratitis