BETA-LACTAM ANTIBIOTICS POTENTIATE MAGAININ-2 ANTIMICROBIAL ACTIVITY INVITRO AND INVIVO

BETA-LACTAM ANTIBIOTICS POTENTIATE MAGAININ-2 ANTIMICROBIAL ACTIVITY INVITRO AND INVIVO
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DOI:
10.1128/aac.35.6.1153
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发表时间:
1991-06-01
影响因子:
4.9
通讯作者:
WATKINS, CS
WATKINS, CS
中科院分区:
医学2区
文献类型:
--
作者:
DARVEAU, RP;CUNNINGHAM, MD;WATKINS, CS

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检查了 magainin 2 增强抗生素治疗的能力。 在体外和体内存在或不存在亚致死浓度抗生素的情况下培养的大肠杆菌测定了对 magainin 2 的敏感性。 在缓冲液和正常人血清中进行的实验表明,暴露于亚致死量的头孢吡肟(一种 β-内酰胺类抗生素)的大肠杆菌对马盖宁 2 的抗菌活性显着更敏感。在正常人血清中,与亚抑制浓度的其他 β-内酰胺类抗生素(但不是阿米卡星(一种氨基糖苷类))或环丙沙星(一种喹诺酮类药物)一起培养的细菌也对马盖宁 2 更敏感。 当在热灭活血清中进行检查时,细菌对 magainin 2 不太敏感。 通过使用 C8 缺陷血清,表明血清中的 magainin 2 活性需要补体。 Magainin 2 和头孢吡肟的组合在正常人血清中对多种细菌菌株具有更强的抗菌作用。 当单独给予 Magainin 2(每只小鼠 2 毫克)时,Magainin 2 作为治疗剂完全没有活性,但当与低水平的头孢吡肟一起给予时,显着增加了小鼠的存活率。
The ability of magainin 2 to augment antibiotic therapy was examined. Susceptibility to magainin 2 was determined on Escherichia coli incubated in the presence and absence of sublethal concentrations of antibiotics both in vitro and in vivo. Experiments in buffer and normal human serum revealed that E. coli exposed to sublethal amounts of cefepime, a beta-lactam antibiotic, was significantly more susceptibe to the antimicrobial activity of magainin 2. Bacteria incubated with subinhibitory concentrations of other beta-lactam type antibiotics, but not amikacin (an aminoglycoside) or ciprofloxacin (a quinolone), were also more susceptible to magainin 2 in normal human serum. Bacteria were less susceptible to magainin 2 when they were examined in heat-inactivated serum. Complement was shown to be required for magainin 2 activity in serum by using C8-deficient sera. The combination of magainin 2 and cefepime was shown to be more antimicrobial in normal human serum for a variety of bacterial strains. Magainin 2 was completely inactive as a therapeutic agent when it was administered alone (2 mg per mouse) but significantly increased the survival of mice when it was administered with a low level of cefepime.