スルホ化免疫グロブリン製剤のペニシリン耐性肺炎球菌及び緑膿菌に対する抗菌活性 Anti-bacterial Activities of a Sulfonated Human Immunoglobulin Preparation againsr Penicillin Resistant Streptococcus pneumoniae and Pseudomonas

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免疫不全患者での耐性菌感染の化学療法は困難である.この場合, 抗体を追加あるいは代替治療に用いることが考えられる.そこでヒト免疫グロブリン製剤の抗菌活性を調べた.<BR>血清型19肺炎球菌のペニシリン耐性および感性菌株のCBA/Jマウスに対する50%致死量はそれぞれ2.8×10<SUP>6</SUP>, 8.7×10<SUP>5</SUP>CPUであった.およそ10LD<SUB>50</SUB>の菌で攻撃したマウスの50%を生残させる被験製剤量はそれぞれ4.1, 2.Omgであった.また, <I>in vitro</I>のMICはそれぞれ10, 20mg/mlであった.被験製剤存在下でのPIPC, FMOX, IPM, AMKおよびOFLXのMICを調べた.全薬物のMICは被験製剤の濃度とともに低下し, 免疫グロブリンは化学療法薬と相乗的な抗菌活性を示すことが判った.同様な加<I>in vitro</I>試験を緑膿菌でも行った.被験製剤の緑膿菌に対するMIC値は40mg/ml以上であった.しかし, 被験製剤存在下での抗菌剤のMICは低下し, 免疫グロブリンが化学療法薬と相乗的に抗菌活性を現すことは緑膿菌でも確認された.<BR>以上の結果から, 被験製剤の肺炎球菌感染マウスに対する治療効果は, ペニシリン感受性, 耐性に関係なく感染菌量に比例し, 血清型19の菌株では10<SUP>6</SUP>菌/1-2mgであることが判った.これを<I>in vitro</I>のMICと比べると, <I>in vivo</I>の殺菌活性は100倍で, 生体内では殺菌効果が高いことが示唆された.また, 化学療法との相乗効果が示唆され, MICより低い濃度でも併用によって効果を現すことが示唆された.緑膿菌でも同様な可能性が示唆された.

Anti-bacterial activities of a sulfonated human immunoglobulin preparation against penicillin resistant <I>Streptococcus pneumoniae</I> and <I>Pseudomonas aeruginosa</I> were examined. Five week old CBA/J mice were challenged by 10 times of 50% lethal doses of penicillin sensitive (SP1) and resistant (SP2) strains of <I>Streptopcoccus pneuminiae </I>serotype 19, and were treated with a sulfonated human immunoglobulin preparation (hIg). Fifty % protective dose (ED<SUB>50</SUB>) were 2-4mg hIg/ mouse. These doses were parallel with the challenged doses despite of the challenged bacteria, and it was calculated that 6×10<SUP>6</SUP> bacteria were killed by one mg of hIg in both bacteria.<BR>Minimal inhibitory concentrations (MIC) of piperacillin, flomoxef, imipenem, amikacin and ofloxacin against SP1 and SP2 were estimated under the presence of various concentrations of hIg. It was found that under the presence of over 10-20 mg/ml of hIg, SP1 and SP2 were not grown even without any antobiotic. That is, MIC of hIg itself against penicillin sensitive and resistant <I>Streptococcus pneumoniae</I>(HR) serotype 19 were 10-20 mg/ml. Since about 10<SUP>6</SUP> bacteria/ml were used for this test, it was calculated that 5-10×10<SUP>4</SUP> bacteria were killed by one mg of hIg<I>in vitro</I>. This result suggested that <I>in vivo</I> anti-bacterial activities of hIg could be 100 times higher than that <I>in vitro</I>. Synergistic or at least additive effects between hIg and all antibiotics tested were seen by the MIC. If hIg was 100 times effective in <I>in vivo</I>, these results suggested that hIg could improve the effect of chemotherapy in clinical cases.<BR>Similar <I>in vitro</I> test were carried out for <I>Pseudomonas aeruginosa</I>, and synergistic or at least additive effects between hIg and all antibotics tested were also confirmed in Pseudomonas aeruginosa. This result suggested that hIg could be effective for clinical <I>pseudomonas infection</I>.

収録刊行物

  • 感染症学雑誌 : 日本伝染病学会機関誌 : the journal of the Japanese Association for Infectious Diseases

    感染症学雑誌 : 日本伝染病学会機関誌 : the journal of the Japanese Association for Infectious Diseases 71(8), 738-744, 1997-08-20

    The Japanese Association for Infectious Diseases

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各種コード

  • NII論文ID(NAID)
    10008721366
  • NII書誌ID(NCID)
    AN00047715
  • 本文言語コード
    JPN
  • 資料種別
    ART
  • ISSN
    03875911
  • NDL 記事登録ID
    4306169
  • NDL 雑誌分類
    ZS9(科学技術--医学--病理学・微生物学・寄生虫学・感染・免疫学・血清学・アレルギー)
  • NDL 請求記号
    Z19-193
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
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