LAUSR

Historically, Aspergillus fumigatus is the most common cause of invasive aspergillosis, but recent genetic analysis has identified Aspergillus lentulus as a variant species. Here, we report a pediatric case of probable invasive pulmonary aspergillosis (IPA) caused by A. lentulus, which was successfully treated with micafungin. A 12-year-old boy with refractory nephrotic syndrome due to biopsy-proven focal segmental glomerulosclerosis was treated with rituximab, followed by three courses of high-dose methylprednisolone therapy and maintenance immunosuppression with prednisolone and mycophenolate mofetil. Three weeks after rituximab treatment, he developed rhinorrhea and a non-productive cough that lasted for 1 week. He had no fever and physical examination was within normal limits with no adventitious breath sounds on auscultation. On laboratory examination, peripheral blood white blood cell count was 5400/lL and C-reactive protein was <0.2 mg/dL, but b-D-glucan was elevated at 111.7 pg/mL. CD19-positive cells were nearly absent (0.1%). Chest computed tomography (CT; Fig. 1) showed a cavitary lesion in the right upper lobe with a diameter of 17 mm, in contrast to the normal chest/body CT done 2 months prior for the assessment of ascites. Aspergillus spp. was isolated from sputum culture and from the bronchoalveolar lavage (BAL) fluid. The patient was diagnosed with probable invasive fungal disease according to the European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria in 2008. He was empirically treated with standard oral maintenance dose of voriconazole (100 mg/dose, twice daily; based on adult dose for patients <40 kg) for IPA without the initial i.v. loading dose due to concerns regarding impaired renal function. Prednisone dose was reduced as well. Despite 2 weeks of voriconazole and adequate serum trough concentration 2.1 lg/ mL, the cavitary lesion increased in size, to a diameter of 20 mm on chest CT. Four weeks after treatment, the Aspergillus spp. cultured from sputum and BAL was ultimately identified as A. lentulus on b-tubulin sequencing, and susceptibility testing was performed based on CLSI M38-A2 broth microdilution methods. The partial sequence of b-tubulin was determined using primer pair Bt2a and Bt2b, and was analyzed using BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi). This showed 100% homology with sequence data of 16 strains identified as A. lentulus. The minimum inhibitory concentration (MIC) for amphotericin B, voriconazole, and fluconazole is 4 lg/mL, 4 lg/mL, and >64 lg/mL, respectively, and the minimum effective concentration for micafungin is 0.015 lg/mL. The isolate had low susceptibility to both amphotericin B and voriconazole, and the antifungal therapy was changed to micafungin (150 mg/kg/dose, once daily). The cavitary lesion gradually diminished and resolved completely after 4 months of micafungin.