Comparative efficacies of daptomycin, vancomycin, and linezolid in experimental enterococcal peritonitis
Comparative efficacies of daptomycin, vancomycin, and linezolid in experimental enterococcal peritonitis
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DOI：
10.1016/j.jiac.2016.12.002
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发表时间：
2017-07-01
影响因子：
2.2
通讯作者：
Mukae, Hiroshi
中科院分区：
文献类型：
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作者：
Kajihara, Toshiki;Nakamura, Shigeki;Mukae, Hiroshi
肠球菌已经成为医院感染（例如菌血症、腹腔内感染、心内膜炎等）的越来越重要的病原体，与它们对许多抗生素的内在抗性有关。虽然达托霉素（DAP）对肠球菌的体外敏感性已得到充分证实，但美国食品和药物管理局仅批准其用于由粪肠球菌引起的复杂皮肤和皮肤结构感染。在这项研究中，我们评估了潜在的治疗应用DAP在小鼠模型的肠球菌实验性腹膜炎。小鼠腹腔注射4 × 10（10）个屎肠球菌菌落形成单位。接种肠球菌后2 h分别给予DAP、DAP联合氨苄西林、万古霉素或利奈唑胺，检测存活率、活菌计数和腹腔液中KC/CXCL 1水平。接种肠球菌后6 h和12 h，DAP组或DAP+氨苄青霉素组腹腔液中的活菌数均显著低于万古霉素组和利奈唑胺组（P < 0.05）。接种肠球菌后12 h，DAP+氨苄青霉素组腹腔液中性粒细胞趋化因子KC水平显著降低（P < 0.05）。此外，通过微量生物膜测定，DAP显示出剂量依赖性的肠球菌生物膜形成的抑制作用。这些结果表明，DAP，特别是与β-内酰胺类药物，是一种可能的替代药物，以治疗严重的肠球菌感染，如腹膜炎。(C)2016年日本化疗学会和日本传染病协会。由爱思唯尔有限公司出版。保留所有权利。
Enterococci have become increasingly important pathogens for nosocomial infection (e.g. bacteremia, intra-abdominal infection, endocarditis, etc.), related to their intrinsic resistance to many antibiotics. Although the in vitro susceptibility of daptomycin (DAP) against Enterococci is well established, the Food and Drug Administration has only approved its use for complicated skin and skin structure infections induced by Enterococcus faecalis. In this study we evaluated the potential therapeutic application of DAP in a murine model of enterococcal experimental peritonitis. Mice were injected intraperitoneally with 4 x 10(10) colony-forming units of Enterococcus faecium. DAP alone, DAP combined with ampicillin, vancomycin, or linezolid were administered 2 h after enterococcal inoculation and examined the survival, viable bacteria counts, the level of KC/CXCL1 in the peritoneal fluid. The viable bacteria counts in the peritoneal fluid of the DAP or DAP plus ampicillin-treated groups were decreased significantly compared to those of the vancomycin- and linezolid-treated groups (P < 0.05) at 6 and 12 h after the inoculation of Enterococcus. The level of neutrophil chemoattractants KC in the peritoneal fluid at 12 h after enterococcal inoculation was significantly decreased in the DAP plus ampicillin-treated group (P < 0.05). In addition DAP showed the inhibitory effect of enterococcal biofilm formation dosedependently by a microtiter biofilm assay. These results indicate that DAP, particularly with beta-lactams, is a possible alternative agent to treat severe enterococcal infection such as peritonitis. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.