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首页> 外文期刊>Antimicrobial agents and chemotherapy. >In Vitro Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) against Contemporary Clinical Bacteria from a Global Surveillance Program
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In Vitro Activity of the Novel Lactone Ketolide Nafithromycin (WCK 4873) against Contemporary Clinical Bacteria from a Global Surveillance Program

机译：来自全球监测计划的新型内酯酮酮Nafithromithromitomcin（WCK 4873）的体外活性

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摘要

Nafithromycin (WCK 4873), a novel antimicrobial agent of the lactone ketolide class, is currently in phase 2 development for treatment of community-acquired bacterial pneumonia (CABP). A total of 4,739 nonduplicate isolates were selected from a 2014 global surveillance program at medical institutions located in 43 countries within the United States, Europe, Latin America, and the Asia-Pacific region. Nafithromycin and comparator agents were used for susceptibility testing by reference broth microdilution methods. Nafithromycin was active against Staphylococcus aureus (MIC50/90, 0.06/>2 mu g/ml), including erythromycin-resistant strains exhibiting an inducible clindamycin resistance phenotype (MIC50/90, 0.06/0.06 mu g/ml) and telithromycin-susceptible strains (MIC50/90, 0.06/0.06 mu g/ml), but it exhibited limited activity against most telithromycin-resistant and clindamycin-resistant isolates that were constitutively resistant to macrolides (MIC50/90, >2/>2 mu g/ml). Nafithromycin was very active (MIC50/90, 0.015/0.06 mu g/ml) against 1,911 Streptococcus pneumoniae strains, inhibiting all strains, with MIC values of <= 0.25 mu g/ml. Telithromycin susceptibility was 99.9% for Streptococcus pneumoniae strains, and nafithromycin was up to 8-fold more potent than telithromycin. Overall, 37.9% of S. pneumoniae strains were resistant to erythromycin, and 19.7% were resistant to clindamycin. Nafithromycin was highly active against 606 Streptococcus pyogenes strains (MIC50/90, 0.015/0.015 mu g/ml), inhibiting 100.0% of isolates at <= 0.5 mu g/ml, and MIC50/90 values (0.015/0.015 to 0.03 mu g/ml) were similar for the 4 geographic regions. Nafithromycin and telithromycin demonstrated comparable in vitro activities against 1,002 Haemophilus influenzae isolates and 504 Moraxella catarrhalis isolates. Overall, nafithromycin showed potent in vitro activity against a broad range of contemporary (2014) global pathogens. These results support the continued clinical development of nafithromycin for treatment of CABP.
机译：Nafithromycin（WCK 4873）是一种新型内酯酮酮类的新型抗微生物剂，目前处于2阶段，用于治疗社区收购的细菌性肺炎（CABP）。共有4,739个非普化的孤立液，选自2014年在美国，欧洲，拉丁美洲和亚太地区43个国家的医疗机构的2014年全球监督计划中。 Nafithromycin和比较剂通过参考肉汤微脱离方法用于易感性测试。 Nafithromycin对葡萄球菌（MIC50 / 90,0.06 />2μg/ ml）有效，包括抗诱导型Clindamycin抗性表型（MIC50 / 90,0.06 / mm G / ml）和汽油霉素易感菌株的红霉素抗性菌株（MIC50 / 90,0.06 /0.06μg/ ml），但它表现出对大多数致铬霉素的抗性和克林霉素抗性分离物具有有限的活性，该抗性和克林霉素抗性分离物构成抗大溴化硼（MIC50 / 90，> 2μg/ mL） 。 Nafithromycin非常活跃（MIC50 / 90,0.015 /0.06μg/ ml），其抑制所有菌株，抑制所有菌株，MIC值<=0.25μg/ ml。肺炎链球菌菌株的汽油霉素易感性为99.9％，而且萘霉素高达8倍的高效菌素。总体而言，37.9％的S.肺炎菌株对红霉素具有抗性，19.7％对Clindamycin具有抗性。 Nafithromycin对606链球菌（MIC50 / 90,0.015 / ml）高度活性，抑制<=0.5μg/ ml的100.0％的分离物，MIC50 / 90值（0.015 / 0.015至0.03μg / ml）类似于4个地理区域。 Nafithromycin和Telitroomycin证明了对1,002个嗜血杆菌的体外活性相当的体外活性和504个Moraxella catarrhalis分离物。总体而言，Nafithromycin对广泛的当代（2014）全球病原体显示出有效的体外活动。这些结果支持Nafithromycin的持续临床开发用于治疗CABP。

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