The First Korean Case of Disseminated Mycetoma Caused by Nocardia pseudobrasiliensis in a Patient on Long-Term Corticosteroid Therapy for the Treatment of Microscopic Polyangiitis
A 57-yr-old woman was admitted to the emergency department of our hospital on July 3, 2012. She had tender erythematous nodules scattered on her scalp, right arm, right leg, and abdomen that had developed 2 weeks earlier (). Despite a 3-day course of cefaclor that was prescribed by the primary hospital, the lesions had not subsided. In addition, for the past 3 months, she had been on corticosteroid therapy for the treatment of pulmonary microscopic polyangiitis. One year earlier, she had been diagnosed with end-stage renal disease, necessitating hemodialysis 3 times a week.\nHer blood pressure in the emergency department was 152/102 mmHg; she had a pulse rate of 120/min, a respiration rate of 20/min, and a body temperature of 38.4℃. Active lung lesions were not observed on the chest radiograph. The results of a complete blood cell count were as follows: white blood cell count, 17.4×109/L; hemoglobin, 10.6 g/dL; and platelet count, 306×109/L. Her serum C-reactive protein level was 50.29 nmol/L.\nBiopsies of the nodules on her scalp, right arm, and right leg revealed inflammation and pus formation, which were evident on hematoxylin and eosin stained histological preparations (); many neutrophils but no organisms were detected by Gram staining. The 3 sets of blood cultures taken at admission were negative. Bacterial and fungal cultures of the biopsied tissues from mycetomas on the patient's scalp, right arm, and right leg yielded tiny white colonies on blood agar and Sabouraud dextrose agar after a 2-day incubation. Over time, the colonies grew larger, taking on an irregular wrinkled appearance with an orange color and a chalky white powder covering (). The responsible organism consisted of thin, filamentous branching, Gram-positive, and modified Kinyoun-positive rods ().\nTests of the organism for catalase and urease were positive, as were those for casein, hypoxanthine, and tyrosine hydrolysis, whereas opacification of 7H10 agar and hydrolysis of xanthine were not observed (, ). A culture prepared in tap water agar revealed growth of the isolate with aerial hyphae. In the other biochemical tests performed using API Coryne and API 20C AUX (BioMèrieux, Marcy l'Etoile, France), the organism was negative for nitrate reductase, positive for esculin and gelatin hydrolysis, and positive for the assimilation of glucose, glycerol, galactose, N-acetyl-D-glucosamine, inositol, and trehalose. Growth of the isolate at 45℃ was poor after a 3-day incubation. Most of these phenotypic results were consistent with both N. brasiliensis and N. pseudobrasiliensis, with the latter more likely based on the negative nitrate reductase test.\nIn direct PCR sequencing of 1,350 bp of 16S rRNA obtained from the isolate, 99.5% (1,305/1,312) homology with the published sequence of N. pseudobrasiliensis ATCC 51512T and 98.3% homology with that of N. otitidiscaviarum DSM 43242T were determined. In addition, the hsp65 sequence of the organism exhibited 99.5% (408/410) homology with the corresponding sequence of N. pseudobrasiliensis strain DSM 44290T and 97.3% homology with that of N. transvalensis strain DSM 46068T []. In line with the CLSI guidelines [], the organism was identified as Nocardia, most closely related to N. pseudobrasiliensis. The organism was finally identified as N. pseudobrasiliensis based on its phenotypic characteristics and 16S rRNA and hsp65 gene sequencing.\nAfter the patient was treated with a 5-day course of intravenous ampicillin/sulbactam as an empirical therapy for end-stage renal disease, the multiple mycetomas and fever subsided. She was discharged with a 1-month prescription for amoxicillin/clavulanate. The patient was successfully treated with 6 months of antibiotics therapy.\nThe organism was tested for antimicrobial susceptibility by the broth microdilution method, performed using the Sensititre Rapid Growing Mycobacteria Plate Format (TREK Diagnostic Systems Limited, East Grinstead, UK). The inoculum was prepared in BACTEC Plus Aerobic/F medium (Becton Dickinson Diagnostic Systems, Sparks, MD, USA) instead of cation-adjusted Mueller-Hinton broth, because the organism grew poorly in the latter. The test results revealed a minimal inhibitory concentration (MIC) of 8/152 for trimethoprim/sulfamethoxazole (TMP/SMX). The MICs of other antibiotics were as follows: ciprofloxacin, ≤0.12; moxifloxacin ≤0.25; cefoxitin, >128; amikacin, 4; doxycycline, 16; tigecycline, 4; clarithromycin, 0.25; linezolid, ≤1; imipenem, 64; cefepime, 16; amoxicillin/clavulanate, 32/16; ceftriaxone, 8; minocycline, >8; and tobramycin, ≤1. These data suggested resistance against TMP/SMX, cefoxitin, doxycycline, imipenem, amoxicillin/clavulanate, and minocycline [].