緑膿菌呼吸器感染症に対するTobramycin,Cefsulodin,Fosfomycin3剤の併用療法  FIC indexと治療効果について:FIC indexと治療効果について  [in Japanese] Study of combined therapy of tobramycin-cefsulodin-fosfomycin for respiratory tract infections caused by Pseudomonas aeruginosa. Relation between FIC index and clinical efficacy.:RELATION BETWEEN FIC INDEX AND CLINICAL EFFICACY  [in Japanese]

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Author(s)

    • 陳 瑞明 CHEN RUEY-MEI
    • 千葉大学医学部肺癌研究施設内科 Department of Internal Medicine, Institute of Pulmonary Cancer Research, School of Medicine, Chiba University
    • 菊池 典雄 KIKUCHI NORIO
    • 千葉大学医学部肺癌研究施設内科 Department of Internal Medicine, Institute of Pulmonary Cancer Research, School of Medicine, Chiba University
    • 村木 憲子 MURAKI NORIKO
    • 千葉大学医学部肺癌研究施設内科 Department of Internal Medicine, Institute of Pulmonary Cancer Research, School of Medicine, Chiba University
    • 長尾 啓一 NAGAO KEIICHI
    • 千葉大学医学部肺癌研究施設内科 Department of Internal Medicine, Institute of Pulmonary Cancer Research, School of Medicine, Chiba University
    • 栗山 喬之 KURIYAMA TAKAYUKI
    • 千葉大学医学部肺癌研究施設内科 Department of Internal Medicine, Institute of Pulmonary Cancer Research, School of Medicine, Chiba University
    • 渡辺 昌平 WATANABE SHOHEI
    • 千葉大学医学部肺癌研究施設内科 Department of Internal Medicine, Institute of Pulmonary Cancer Research, School of Medicine, Chiba University

Abstract

呼吸器感染症の起炎菌として, 喀痰より分離された緑膿菌に対し, 菌分離時に<I>in vitro</I>でTobramycin (TOB) +Cefsulodin (CFS) +Fosfomycin (FOM) の併用効果を検討した。その結果, 相乗効果 (FIC index≦0.5) が認められた緑膿菌による呼吸器感染症33症例 (A群: 慢性呼吸器感染症の増悪13例, B群: 続発性肺炎19例, C群: その他1例) に対して, この3剤併用療法を臨床応用し, 治療効果を検討した。<BR>1) 対象症例より分離された新鮮緑膿菌33株に対するTOB, CFSおよびFOMの80%MICは4μg/ml, 32μg/mlおよび128μg/mlであった。TOB+CFSにFOM 8または32μg/mlを添加した際のFIC indexは0.12~0.50であった。<BR>2) 細菌学的効果は菌消失24例, 減少9例で, 菌消失率は72.7%であった。総合臨床効果は, 著効14例, 有効19例で, 有効以上の改善率は100%であった。重篤な副作用は1例もみられなかった。<BR>3) CFS 1.0あるいは2.0g, FOM 2.0gを1時間かけて, 点滴静注し, 同時にTOB 60mgを筋注した際の最高血中濃度は, 投与1時間にピークに達し, CFS 1.0g投与群 (3例) 77.2±24.3μg/ml, 2.09投与群 (6例) 101.0±27.9μg/ml, FOM 2.0g群 (9例) 130.6±44.4μg/ml, TOB 60mg群 (9例) 4.5±2.3μg/mlであった。最高喀痰中移行濃度は, A群 (4例) では, CFS 3.4±2.4μg/ml, FOM 7.3±4.0μg/mlおよびTOB 0.9±0.2μg/ml, B群 (3例) では, CFS 3.8±3.5μg/ml, FOM 10.6±7.3μg/mlおよびTOB 1.5±0.9μg/mlであった。<BR>4)<I>In vitro</I>での殺菌効果は, 抗菌剤単独投与に比較し, 併用では明らかに増強された。<BR>緑膿菌呼吸器感染症の治療指針として, MICの検査とともにFIC indexの測定は極めて有用と考えられた。

Thirty-three cases (Group A: Acute exacerbation of chronic respiratory tract infection, 13 cases. Group B: Pneumonia, 19 cases. Group C: Other, 1 case) of respiratory tract infections caused by <I>P. aeruginosa</I> were administrated the combination of TOB+CFS+FOM which was <I>in vitro</I> synergistic (FIC index≤0.5) against the fresh isolated <I>P. aeruginosa</I>, and clinical efficacy of this combination was evaluated.<BR>1) The MICs 80 of TOB, CFS and FOM against 33 freshly isolated <I>P. aeruginosa</I> from the 33 cases were 4μg/ml, 32μg/ml and 128μg/ml, respectively. The ranges of FIC index of addition of FOM to TOB+CFS were 0.12-0.50.<BR>2) Bacteriologically, 24 and 9 out of 33 cases were eradicated and reduced, respectively. Twentyfour (72.7%) out of 33 cases were eliminated. Clinical efficacies resulted in 14 excellent and 19 good cases. Clinical efficacies of both excellent and good were observed in all 33 cases. Concerning side effects, no severe one was observed.<BR>3) After intravenous drip infusion of 1.0g or 2.0g CFS, 2.0g FOM for one hour and intramuscular administration of 60mg TOB, the serum concentration of each drug reached peak level at one hour in nine cases. The peak of serum concentration was 77.2±24.3 and 101.0±27.9±g/ml, respectively following 1.0g (3 cases) and 2.0g (6 cases) drip infusion of CFS. The peak of serum concentration was 130. 6± 44. 4μg/ml following 2.0g (9 cases) of FOM and 4.5±2.3μg/ml following 60mg (9 cases) of TOB. In Group A (4 cases) the peak of sputum concentrations of CFS, FOM and TOB were 3.4±2.4μg/ml, 7.3±4.0μg/ml and 0.9±0.2μg/ml, respectively, in Group B (3 cases) 3.8±3.5μg/ml, 10.6±7.3μg/ml and 1.5±0.9μg/ml, respectively.<BR>4) <I>In vitro</I> time-kill studies, antibiotic combination showed stronger bactericidal effects against the isolated strains of <I>P. aeruginosa</I> than single drug.<BR>We propose that measurements of MIC and FIC index may be a useful guide for treatment of respiratory tract infection caused by <I>P. aeruginosa</I>.

Journal

  • CHEMOTHERAPY

    CHEMOTHERAPY 34(8), 688-704, 1986

    Japanese Society of Chemotherapy

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