Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection

Effects of a human antiflagellar monoclonal antibody in combination with antibiotics on Pseudomonas aeruginosa infection
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人抗鞭毛单克隆抗体联合抗生素对铜绿假单胞菌感染的影响

DOI:
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发表时间:
1992
影响因子:
4.9
通讯作者:
H. Noguchi
H. Noguchi
中科院分区:
医学2区
文献类型:
--
作者:
I. Uezumi;M. Terashima;T. Kohzuki;M. Kato;K. Irie;H. Ochi;H. Noguchi

文献摘要

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与抗O抗原(血清型B)MA B KO-2F 2相比并与抗生素组合,评价了对铜绿假单胞菌鞭毛型B具有特异性的人免疫球蛋白M单克隆抗体IN-2A 8的体内活性。IN-2A 8对烧伤小鼠皮下感染的抑制活性强于KO-2F 2,而对正常小鼠腹腔感染的抑制活性低得多。在烧伤感染模型中,IN-2A 8对皮肤病变中细菌的增加有微弱的抑制作用,而对血液中细菌的增加有显著的抑制作用,这表明它强烈地抑制了细菌向血液的传播。检查IN-2A 8与10种抗假单胞菌抗生素组合对抗腹膜内感染的活性。在小鼠存活率方面,观察到碳青霉烯类或氨基糖苷类抗生素组合的明显累加效应。与IN-2A 8同时或在IN-2A 8之前给予抗生素亚胺培南-西司他丁产生了联合作用,但相反的顺序则没有。IN-2A 8与亚胺培南-西司他丁的组合减少了腹膜腔和血液中活菌的数量,并使其保持在较低水平的时间比单独使用任何一种治疗都长。这些结果表明,抗鞭毛单克隆抗体与某些抗生素联合使用可有效对抗全身性感染。
The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infection in burned mice, while it was much less active against intraperitoneal infection in normal mice. In a burn infection model, IN-2A8 inhibited the increase of bacteria in skin lesions weakly and that in blood significantly, suggesting that it strongly suppressed bacterial spread to blood. The activity of IN-2A8 in combination with 10 antipseudomonal antibiotics against intraperitoneal infection was examined. Clear additive effect was observed with a combination of either carbapenem or aminoglycoside antibiotics in terms of mouse survival. The administration of an antibiotic, imipenem-cilastatin, simultaneously with or before that of IN-2A8 gave a combined effect, but the reverse order did not. The combination of IN-2A8 with imipenem-cilastatin decreased numbers of viable bacteria in the peritoneal cavity and blood and kept them low for a longer time than did either treatment alone. These results suggest that an antiflagellar monoclonal antibody would be effective against systemic infection in combination with some kinds of antibiotics.