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下肢慢性皮膚損傷部からkerstersia Gyiorumが検出された 1例

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下肢慢性皮膚損傷部からkerstersia Gyiorumが検出された 1例 症例報告 日集中医誌 2017;24:337-40. 下肢慢性皮膚損傷部からKerstersia gyiorumが検出された 1例 杉浦 潤＊1 間藤 卓＊1 関根 進＊2 有馬 史人＊1 大井 秀則＊1 山口 充＊1 中田 一之＊1 杉山 聡＊1 要約：70歳，男性。下肢の慢性皮膚損傷の悪化による重症敗血症にて，近医より紹介となった。 積極的な創部の処置と抗菌薬投与にて敗血症状態を脱し軽快した。後日，創部の培養から， Kerstersia gyiorum（K. gyiorum）が検出された。近年，16S rRNA（16S ribosomal RNA）解析に よる細菌の分類，同定が進んでおり，K. gyiorumは2003年に分類された菌であるが未だ報告例 は乏しい。報告が少ない理由として同定の困難さが挙げられる。今回の症例は，MALDI-TOF MS（matrix assisted laser desorption/ionization time of flight mass spectrometry）法により 同定が行われた。検査機器の進歩に伴い，解析が医療施設で行えるようになったため，これ まで同定が困難であった菌が，比較的容易に同定できるようになり，今後は，今回と同じく， これまで我々があまり聞き慣れない，過去に報告の少ない菌が同定されるケースが増えるこ とが容易に予想される。症例の蓄積と，治療に関する知識の集積が望まれる。 Key words: ①MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry), ②16S rRNA (16S ribosomal RNA) 下肢の切断が必要と判断されたため，当院に転送され はじめに た。 慢性皮膚損傷とは，6週以上続く，または繰り返す 初診時現症：意識レベルGCS E3V3M6，血圧 皮膚の損傷を呈する病状であり，基礎疾患を有する症 111/61 mmHg，心拍数133 /min整，呼吸数30 /min， 例が多い。感染を合併すると，創傷治癒の遷延や全身 SpO2 97％ （室内気），体温37.6℃，るいそう著明，両 状態の悪化を来す場合がある。今回，下肢の慢性皮膚 側下腿を含め複数箇所に潰瘍を認め，創周囲の発赤と 損傷部にKerstersia gyiorum（K. gyiorum）を起因菌 悪臭を認めた（Fig. 1）。 とする感染を呈した1例を経験した。この菌を起因菌 初診時検査所見：WBC 23,900 /μl，CRP 18.9 mg/ とする症例報告は少ないことから，若干の考察を交え dlと炎症反応の上昇があり，Hb 6.7 g/dlと貧血を認 て報告する。 めた。HbA1cは5.3％と正常値であった。 臨床経過：収容時，意識障害を認め，重症敗血症と 症 例 して治療を開始した。輸液蘇生，赤血球輸血を行い， 症例：70歳，男性。 創部，血液培養を提出後，メロペネム1 gを1日3回， 主訴：全身の痛み。 バンコマイシン1 gを1日2回の投与を開始し，創部は 既往歴：クローン病，ステロイド糖尿病（5年前に通 デブリードマンを施行した。 院を自己中断し未治療）。 翌日には意識レベルはGCS E4V4M6と改善し，創 現病歴：数年前より両下肢に皮膚の潰瘍が出現し， 周囲の炎症所見も改善した。創部培養の途中報告でグ 自己処置をしていた。受診4週間前より徐々に活動性 ラム陽性球菌は極少量で，グラム陰性桿菌が多数を占 が低下，受診前日より会話困難，受診日当日に歩行不 めていたことから，バンコマイシンの投与を中止しメ 能となり近医を受診した。両下腿に広範な壊疽を認め， ロペネム単剤で治療を継続した。創部を含めた身体所 ＊1埼玉医科大学総合医療センター高度救命救急センター，＊2同 中央検査部 受付日2016年 5 月 2 日 （〒350-8550 埼玉県川越市鴨田1981） 採択日2016年10月 6 日 －337－ 日集中医誌 J Jpn Soc Intensive Care Med Vol. 24 No. 3 Fig. 1 Leg ulcers at time of hospitalization Fig. 2 Colony of Kerstersia gyiorum〔TSAⅡ 5％ Sheep 見が改善し，安定したことから第5病日に紹介元病院 Blood Agar M（日本ベクトン・ディッキンソン）〕 へ転院となった。転院後も創部の感染は悪化を認めず， 第33病日にリハビリ病院へ転院となった。 創部培養では，K. gyiorum（Fig. 2, 3），Proteus mirabilis，Enterococcus faecalisが検出された。真菌 や抗酸菌は検出されず，血液培養も陰性であった。 考 察 今回，創部から検出されたK. gyiorumは，Proteo- bacteria門Betaproteobacteria綱Burkholderiales目 Alcaligenaceae科に分類されるグラム陰性桿菌であ り，2003年にCoenyeらにより初めて同定された。本 菌はAlcaligenes faecalisと生化学的性状が近いとされ ているが，Alcaligenaceae科の他の菌と異なり，オキ シダーゼが陰性で，果実臭を産生しないことが特徴で Fig. 3 Gram-negative coccobacilli ある 1) 。 これまで慢性中耳炎（5例）2)〜5)，下肢の創（3例，う ち菌血症合併1例）4),6),7)，気管支肺胞洗浄液（1例）8)， 例 4),5)，中等度耐性1例 8)と，アズトレオナム，スルファ 尿路（1例）9)から分離された10例の症例が報告された メトキサゾール・トリメトプリム耐性，レボフロキサ のみである。常在菌の可能性も指摘されており，慢性 シン，チカルシリン・クラブラン酸中等度耐性1例5) 炎症部位からの報告が多いが，重症化し敗血症の報告 を認めた。アミノグリコシド系，カルバペネム系への も存在する。 耐性は認めなかった。いずれの報告においても耐性化 このような知見の蓄積が少ない細菌において問題と の機序は検討されていない。本症例もCLSIのother なるのが治療法である。 non-enterobacteriaceaeの判定基準を用いて薬剤感受 K. gyiorumの治療に関して，米国臨床検査標準化 性を検討し，アズトレオナム耐性，シプロフロキサシ 協会（Clinical and Laboratory Standards Institute, ン中等度耐性を認めた（Table 1）。 CLSI）には本菌単独の感受性判定基準が存在せず，過 多剤に耐性報告があることから，感受性判明までは 去の報告ではCLSIのother non-enterobacteriaceaeの 広域抗菌薬の使用も検討される。本症例はメロペネム 基準を用いて8症例で感受性が検討されてい で治療が可能であったが，今後薬剤感受性や治療経験 る 2)〜6),8) 。そのうち菌血症の1例では，セフタジジム， の蓄積が求められる。 セフェピム，タゾバクタム・ピペラシリン耐性，セフォ しかし，現時点での報告例は上述したように多くな タキシム中等度耐性を認めた 6) 。また，その他の症例 い。報告例が少ない原因として，K. gyiorumが細菌 では，シプロフロキサシンに対して7症例中耐性3 学上独立して分類された時期が新しく，確実な同定に －338－ Kerstersia gyiorumによる下肢感染症の1例 Table 1 Antimicrobial susceptibility of the Kerstersia gyiorum Antimicrobial agent MIC（μg/ml） Interpretation AZT ＞16 Resistant PIPC 16 Susceptible TAZ/PIPC ＜8 Susceptible IPM/CS ＜1 Susceptible MEPM ＜1 Susceptible CTX ＜1 Susceptible CTRX ＜1 Susceptible CAZ ＜4 Susceptible CZOP ＜4 Susceptible CFPM ＜2 Susceptible AMK ＜4 Susceptible GM ＜2 Susceptible TOB ＜4 Susceptible MINO ＜2 Susceptible LVFX ＜0.5 Susceptible CPFX 2 Intermediate STFX ＜1 Susceptible ST ＜2 Susceptible Interpretations were assessed in accordance with CLSI criteria for other non-enterobacteriaceae. AMK, amikacin; AZT, aztreonam; CAZ, ceftazidime; CFPM, cefepime; CLSI, Clinical and Laboratory Standards Institute; CPFX, ciprofloxacin; CS, cilastatin; CTRX, ceftriaxone; CTX, cefotaxime; CZOP, cefozopran; GM, gentamicin; IPM, imipenem; LVFX, levofloxacin; MEPM, meropenem; MIC, minimum inhibitory con- centration; MINO, minocycline; PIPC, piperacillin; ST, sulfamethoxazole-trime- thoprim; STFX, sitafloxacin hydrate; TAZ, tazobactam; TOB, tobramycin. は16SリボソームRNA（16S ribosomal RNA, 16S 分類学上16S rRNA塩基配列に基づく系統解析の登 rRNA）の解析や，マトリックス支援レーザー脱離イ 場は画期的で，K. gyiorumに限らず，近年本法に基づ オン化飛行時間型質量分析法（matrix assisted laser く系統解析により，原核生物の分類は大きく変貌し， desorption/ionization time of flight mass 新たな種も多数分類された。本症例は，通常臨床現場 spectrometry, MALDI-TOF MS）による分析が必要で の医師があまり意識しない細菌の分類学の進歩と，細 あり，多くの施設においては実施が困難なことが挙げ 菌検査室の検査機器の進歩により，これまで聞き慣れ られる。他方，当院では，2014年10月より菌種の同 ない起因菌による感染症が増える可能性と，使用する 定方法において，従来の生化学的性状検査に加え 抗菌薬選択の困難さを身をもって体験した貴重な例で MALDI-TOF MSによる分析が追加された。 もあった。今後は検査機器の普及により多施設で MALDI-TOF MS導入後の1年間で，当院では本症例 K. gyiorumの検出が増えることが予想され，本菌に を含めて2例の検体からK. gyiorumが検出された。 対する抗菌薬の感受性および治療経験の蓄積とそれら 導入以前はK. gyiorumの報告例がなく，同定不能ま を啓蒙していくことが望まれる。 たはブドウ糖非発酵グラム陰性桿菌（Pseudomonas まとめ oryzihabitans，Burkholderia cepacia，Acinetobacter spp. など）と報告されていた可能性が高い。 下肢の慢性皮膚損傷部からK. gyiorumが検出され 他施設では，MALDI-TOF MSで同定した菌につい た1例を経験した。時には敗血症を来し，耐性の報告 て，さらに16S rRNA解析を行い，本菌と確定して報 もあることから，さらなる症例の蓄積と研究が進むこ 告しているが4),5),8),9)，今回の症例ではMALDI-TOF とで，より的確な治療方法の確立が期待される。 MSでの同定結果がscore 2.241と高い精度であり，生 化学的性状も矛盾がないことから，これ以上の解析は 行わなかった。 －339－ 日集中医誌 J Jpn Soc Intensive Care Med Vol. 24 No. 3 Kerstersia gyiorum in Tanzania: is it an underappreciated 謝 辞 pathogen in chronic otitis media?. Int J Infect Dis 2014;29: 251-3. K. gyiorumおよび細菌の同定方法についてご教示いただ 4) Pence MA, Sharon J, McElvania Tekippe E, et al. Two いた，当院臨床検査部三橋知明教授に感謝いたします。 cases of Kerstersia gyiorum isolated from sites of chronic infection. J Clin Microbiol 2013;51:2001-4. 本稿の全ての著者には規定されたCOIはない。 5) Uysal EB, Çelik C, Tuzcu N, et al. A case of chronic suppurative otitis media caused by Kerstersia gyiorum. APMIS 2015;123:986-9. 文 献 6) Bostwick AD, Zhang C, Manninen K, et al. Bacteremia caused by Kerstersia gyiorum. J Clin Microbiol 2015;53: 1) Coenye T, Vancanneyt M, Cnockaert MC, et al. 1965-7. Kerstersia gyiorum gen. nov., sp. nov., a novel Alcaligenes 7) Greninger AL, Kozyreva V, Truong CL, et al. Draft faecalis-like organism isolated from human clinical genome sequence of Kerstersia gyiorum CG1, isolated samples, and reclassification of Alcaligenes denitrificans from a leg ulcer. Genome Announc 2015;3:e01036-15. Rüger and Tan 1983 as Achromobacter denitrificans 8) Deutscher M, Severing J, Balada-Llasat JM. Kerstersia comb. nov. Int J Syst Evol Microbiol 2003;53:1825-31. gyiorum isolated from a bronchoalveolar lavage in a 2) Almuzara MN, Barberis CM, Traglia GM, et al. Isolation patient with a chronic tracheostomy. Case Rep Infect Dis of Kerstersia gyiorum from a patient with cholestea- 2014;2014:479581. tomatous chronic otitis media. J Clin Microbiol 9) Ogawa Y, Lee ST, Kasahara K, et al. A first case of 2012;50:3809-11. isolation of Kerstersia gyiorum from urinary tract. J 3) Mwalutende A, Mshana SE, Mirambo MM, et al. Two Infect Chemother 2016;22:265-7. cases of chronic suppurative otitis media caused by Abstract A case of Kerstersia gyiorum detected in a chronic skin lesion on the lower extremity Jun Sugiura＊1, Takashi Mato＊1, Susumu Sekine＊2, Fumihito Arima＊1, Hidenori Oi＊1, Atsushi Yamaguchi＊1, Kazuyuki Nakata＊1, Satoru Sugiyama＊1 ＊1 Department of Emergency and Critical Care Medicine, ＊2 Department of Laboratory Medicine, Saitama Medical Center, Saitama Medical University 1981 Kamoda, Kawagoe, Saitama 350-8550, Japan The patient was a 70-year-old man who was transferred to our hospital by his local physician due to severe sepsis arising from a chronic skin lesion on the lower extremity. Sepsis resolved following aggressive wound treatment and administration of antibiotics. Kerstersia gyiorum (K. gyiorum) was later detected from wound cultures. Progress in the classification and identification of bacteria by 16S rRNA(16S ribosomal RNA) analysis led to the classification of K. gyiorum as a bacterium in 2003, but the number of reported cases remains limited. The difficulty of identifying K. gyiorum is cited as one reason for this lack of reports. In the present case, the bacterium was identified by MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry). Now that analysis is possible at medical facilities due to advances in testing equipment, bacteria that were previously difficult to identify can be relatively easily identified. An increase in the number of cases of identified bacteria that were previously reported only infrequently and that we were previously unaccustomed to hearing about, such as in the present case, is easily conceivable going forward. Further accumulation of cases and knowledge of treatment are anticipated. Key words: ①MALDI-TOF MS (matrix assisted laser desorption/ionization time of flight mass spectrometry), ②16S rRNA (16S ribosomal RNA) J Jpn Soc Intensive Care Med 2017;24:337-40. －340－.
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