Influence of antibiotic and E5 monoclonal immunoglobulin M interactions on endotoxin release from Escherichia coli and Pseudomonas aeruginosa

Influence of antibiotic and E5 monoclonal immunoglobulin M interactions on endotoxin release from Escherichia coli and Pseudomonas aeruginosa
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DOI:
10.1128/aac.40.1.247
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发表时间:
1996-01-01
影响因子:
4.9
通讯作者:
Summers, KK
Summers, KK
中科院分区:
医学2区
文献类型:
--
作者:
Lamp, KC;Rybak, MJ;Summers, KK

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最近围绕抗内毒素单克隆抗体活性的争论突出了确定与死亡率增加相关的所有因素的必要性,其中之一是内毒素浓度。抗生素可诱导不同模式的内毒素释放,我们比较了6小时内游离内毒素的释放(内毒素单位/毫升)以及在化学定义的无内毒素培养基中培养的指数生长的大肠杆菌和铜绿假单胞菌(10(6)至10(7)CFU/ml)的CFU数的变化。与混合的人血清和/或每ml 10 μ g E5免疫球蛋白M单克隆抗体组合的肉汤。在每种培养基中以相同的接种物测试MIC和MBC。将接种物暴露于每种培养基MIC的单一固定倍数的抗生素(范围,2 - 8倍于E5),E5抗体对MIC、MBC、杀菌活性或内毒素释放没有影响。在50%血清存在下,阿米卡星、头孢他啶、亚胺培南和氧氟沙星各自杀死等量的细胞,coli培养6 h;而头孢他啶诱导的内毒素释放量最高,阿米卡星和氧氟沙星产生的内毒素释放量与细菌杀灭量的比率最有利。在50%血清存在下,头孢他啶和亚胺培南在6 h内最大程度地减少铜绿假单胞菌的接种量,尽管其杀菌活性降低,氧氟沙星引起最低的游离内毒素释放,亚胺培南和氧氟沙星显示类似的低内毒素释放与细菌杀灭的比率。总之,抗生素类别、血清存在和微生物类型影响杀菌活性和内毒素释放。
Recent controversy surrounding the activity of monoclonal antibodies against endotoxin highlights the necessity of identifying all factors associated with increased mortality, one of which is endotoxin concentrations. Antibiotics may induce different patterns of endotoxin release, We compared the release of free endotoxin (in endotoxin units per milliliter) over 6 h and changes in numbers of CFU of exponentially growing Escherichia coli and Pseudomonas aeruginosa (10(6) to 10(7) CFU/ml) cultured in chemically defined endotoxin-free. broth combined with pooled human serum and/or 10 mu g of E5 immunoglobulin M monoclonal antibody per ml. MICs and MBCs were tested in each medium at the same inoculum, The inoculum was exposed to antibiotics at a single fixed multiple of the MIC for each medium (range, two to eight times the MIG), E5 antibody had no effect an MICs, MBCs, bactericidal activity, or endotoxin release, In the presence of 50% serum, amikacin, ceftazidime, imipenem, and ofloxacin each killed equivalent amounts off, coli over 6 h; however, ceftazidime induced the highest release of endotoxin, Amikacin and ofloxacin produced the most favorable ratio of endotoxin release to amount of bacterial killing, In the presence of 50% serum, ceftazidime and imipenem reduced the P. aeruginosa inoculum to the greatest extent over 6 h, Although its bactericidal activity was diminished, ofloxacin caused the lowest release of free endotoxin, Imipenem and ofloxacin showed similar low ratios of endotoxin release to bacterial killing, In summary, antibiotic class, presence of serum, and type of organism influenced bactericidal activity and endotoxin release.