脳膿瘍治療中に発症したメトロニダゾール脳症の2例

Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports

Ⅰ．はじめに

　メトロニダゾール（5-nitroimidazole, metronidazole）は，嫌気性菌，トリコモナス，アメーバ，原虫，ヘリコバクター・ピロリ菌に対し，広く使用されている殺菌性の抗菌薬で，髄液移行性に優れるため，嫌気性菌や微好気性菌が多い脳膿瘍治療の標準的治療薬として用いられている^2,3,8,16)．本邦においても2012年6月に公知申請が許可され，適応症に嫌気性菌関連感染症として脳膿瘍が追加記載された¹⁶⁾．半減期は6〜8時間で60%が肝代謝される^12,15)．重要な副作用として，骨髄抑制，肝障害，腎障害，神経障害がある．神経毒性については，末梢神経障害は添付文書上，0.1%未満で発症することが記載されている．また，頻度は不明だが，稀に中枢神経障害を発症することがあり，メトロニダゾール脳症（metronidazole induced encephalopathy：MIE）と呼ばれる¹⁶⁾．MIEは，多彩な症状を来し得るが，典型的には構音障害，小脳失調を呈し，これらの症状は休薬により可逆性である．今回，脳膿瘍治療中にMIEを発症した2症例を提示し，文献的考察を加えて報告する．

　Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy（MIE）during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1：A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2：A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.