In vitro activity of RX-P873 against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii.
In vitro activity of RX-P873 against Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumannii.
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RX-P873 对肠杆菌科、铜绿假单胞菌和鲍曼不动杆菌的体外活性。
DOI：
10.1128/aac.04840-14
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发表时间：
2015
影响因子：
4.9
通讯作者：
Farrell,DavidJ
中科院分区：
文献类型：
--
作者：
Flamm,RobertK;Rhomberg,PaulR;Jones,RonaldN;Farrell,DavidJ
RX-P873是一种新型的吡咯胞嘧啶类抗生素，对细菌核糖体具有很高的亲和力，具有广谱的抗菌特性。吡咯胞嘧啶对多重耐药的革兰氏阴性和革兰氏阳性细菌具有体外活性，已知的细菌会导致复杂的尿路、皮肤和肺部感染，以及败血症。作为全球监测计划的一部分，2012年从北美和欧洲收集的肠杆菌科(657株)、铜绿假单胞菌(200株)和鲍曼不动杆菌(202株)分离株采用临床和实验室标准研究所(CLSI)的微量肉汤稀释法进行了检测。RX-P873(MIC90，0.5μg/ml)的MIC值为≤1和≤4μg/ml，对肠杆菌科细菌的抑制率分别为97.1%和99.5%。只有3株菌的MIC值为~gt；4μg/ml(均为吲哚阳性)。RX-P873(MIC50/90，2/4μg/ml)对铜绿假单胞菌(包括对头孢他啶和美罗培南不敏感的菌株)具有较高的抗菌活性。RX-P873对铜绿假单胞菌的抗菌活性比妥布霉素(MIC90，2μg/ml；敏感率91.0%)和粘菌素(MIC90，2μg/ml；敏感率99.5%)低2倍，比阿米卡星(MIC90，8μg/ml，敏感率93.5%)和美罗培南(MIC90，8μg/ml；敏感率76.0%)强2倍。对鲍曼不动杆菌最有效的抗菌素RX-P873(MIC90，1μg/ml)比粘菌素(MIC90，2μg/ml；敏感率97.0%)高2倍，比替吉环素(MIC90，4μg/ml)高4倍。这种新型药物值得进一步探索其抗多重耐药革兰氏阴性细菌的潜力。
RX-P873 is a novel antibiotic from the pyrrolocytosine series which exhibits high binding affinity for the bacterial ribosome and broad-spectrum antibiotic properties. The pyrrolocytosines have shownin vitroactivity against multidrug-resistant Gram-negative and Gram-positive strains of bacteria known to cause complicated urinary tract, skin, and lung infections, as well as sepsis. Enterobacteriaceae (657), Pseudomonas aeruginosa (200), and Acinetobacter baumannii (202) isolates from North America and Europe collected in 2012 as part of a worldwide surveillance program were testedin vitroby broth microdilution using Clinical and Laboratory Standards Institute (CLSI) methodology. RX-P873 (MIC90, 0.5 μg/ml) was >32-fold more active than ceftazidime and inhibited 97.1% and 99.5% of Enterobacteriaceae isolates at MIC values of ≤1 and ≤4 μg/ml, respectively. There were only three isolates with an MIC value of >4 μg/ml (all were indole-positive Protea). RX-P873 (MIC50/90, 2/4 μg/ml) was highly active against Pseudomonas aeruginosa isolates, including isolates which were nonsusceptible to ceftazidime or meropenem. RX-P873 was 2-fold less active against P. aeruginosa than tobramycin (MIC90, 2 μg/ml; 91.0% susceptible) and colistin (MIC90, 2 μg/ml; 99.5% susceptible) and 2-fold more potent than amikacin (MIC90, 8 μg/ml; 93.5% susceptible) and meropenem (MIC90, 8 μg/ml; 76.0% susceptible). RX-P873, the most active agent against Acinetobacter baumannii (MIC90, 1 μg/ml), was 2-fold more active than colistin (MIC90, 2 μg/ml; 97.0% susceptible) and 4-fold more active than tigecycline (MIC90, 4 μg/ml). This novel agent merits further exploration of its potential against multidrug-resistant Gram-negative bacteria.