替加环素
粘菌素
美罗培南
肺炎克雷伯菌
微生物学
流出
肺炎克雷伯菌
碳青霉烯
抗生素
呼吸机相关性肺炎
多重耐药
生物
肺炎
医学
抗生素耐药性
铜绿假单胞菌
细菌
内科学
基因
大肠杆菌
遗传学
作者
Christoph Stein,Oliwia Makarewicz,Jürgen A. Bohnert,Yvonne Pfeifer,Miriam Kesselmeier,Stefan Hagel,Mathias W. Pletz
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2015-06-11
卷期号:10 (6): e0126479-e0126479
被引量:70
标识
DOI:10.1371/journal.pone.0126479
摘要
The spread of carbapenem-non-susceptible Klebsiella pneumoniae strains bearing different resistance determinants is a rising problem worldwide. Especially infections with KPC (Klebsiella pneumoniae carbapenemase) - producers are associated with high mortality rates due to limited treatment options. Recent clinical studies of KPC-blood stream infections revealed that colistin-based combination therapy with a carbapenem and/or tigecycline was associated with significantly decreased mortality rates when compared to colistin monotherapy. However, it remains unclear if these observations can be transferred to K. pneumoniae harboring other mechanisms of carbapenem resistance. A three-dimensional synergy analysis was performed to evaluate the benefits of a triple combination with meropenem, tigecycline and colistin against 20 K. pneumoniae isolates harboring different β-lactamases. To examine the mechanism behind the clinically observed synergistic effect, efflux properties and outer membrane porin (Omp) genes (ompK35 and ompK36) were also analyzed. Synergism was found for colistin-based double combinations for strains exhibiting high minimal inhibition concentrations against all of the three antibiotics. Adding a third antibiotic did not result in further increased synergistic effect in these strains. Antagonism did not occur. These results support the idea that colistin-based double combinations might be sufficient and the most effective combination partner for colistin should be chosen according to its MIC.
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