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JNJ-Q2 的活性研究,一种新型氟喹诺酮类药物,针对从社区获得性细菌性肺炎患者分离的当代病原体进行测试。

Activity of JNJ-Q2, a new fluoroquinolone, tested against contemporary pathogens isolated from patients with community-acquired bacterial pneumonia.

机构信息

JMI Laboratories, North Liberty, IA 52317, USA.

出版信息

Int J Antimicrob Agents. 2012 Apr;39(4):321-5. doi: 10.1016/j.ijantimicag.2011.11.016. Epub 2012 Feb 4.

DOI:10.1016/j.ijantimicag.2011.11.016
PMID:22306239
Abstract

JNJ-Q2 is a broad-spectrum fluoroquinolone with bactericidal activity against Gram-positive and Gram-negative pathogens and is currently in clinical development for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin-structure infections. This study determined the activity of JNJ-Q2 against a worldwide year 2010 collection (89 centres in 27 countries) of three common respiratory pathogens (3757 isolates) from patients with CABP. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were tested by the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method, and susceptibility rates for comparators were assessed using CLSI and European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoint criteria. JNJ-Q2 had activity against all three species, with 96.9% of strains inhibited at ≤0.015 mg/L. JNJ-Q2 [minimum inhibitory concentration for 50% and 90% of the organisms, respectively (MIC(50/90))=0.008/0.015 mg/L] demonstrated a 16-fold greater potency compared with moxifloxacin (MIC(50/90)=0.12/0.25 mg/L) and at least 128-fold greater activity compared with levofloxacin (MIC(50/90)=1/ 1 mg/L) and ciprofloxacin (MIC(50/90)=1/2 mg/L) against S. pneumoniae. Haemophilus influenzae isolates were 21.9-23.3% resistant to ampicillin, but JNJ-Q2 (MIC(50/90)≤0.004/0.015 mg/L) was at least two-fold more active than moxifloxacin (MIC(50/90)=0.015/0.03 mg/L) as well as being potent against M. catarrhalis (MIC(90)=0.015/0.015 mg/L). In conclusion, JNJ-Q2 demonstrated increased potency compared with other marketed fluoroquinolones that have been used to treat CABP pathogens, thus favouring further clinical development.

摘要

JNJ-Q2 是一种具有广谱杀菌活性的氟喹诺酮类药物,可有效对抗革兰氏阳性和革兰氏阴性病原体,目前正处于治疗社区获得性细菌性肺炎(CABP)和急性细菌性皮肤和皮肤结构感染的临床开发阶段。本研究评估了 JNJ-Q2 对全球 2010 年收集的三种常见呼吸道病原体(来自 27 个国家 89 个中心的 3757 株分离株)的活性,这些病原体来自 CABP 患者。肺炎链球菌、流感嗜血杆菌和卡他莫拉菌采用临床和实验室标准协会(CLSI)肉汤微量稀释法进行检测,使用 CLSI 和欧洲抗菌药物敏感性试验委员会(EUCAST)折点标准评估比较剂的敏感性率。JNJ-Q2 对所有三种病原体均具有活性,96.9%的菌株在≤0.015mg/L 时被抑制。JNJ-Q2 的最低抑菌浓度分别为 50%和 90%的最低抑菌浓度(MIC(50/90)分别为 0.008/0.015mg/L),与莫西沙星(MIC(50/90)为 0.12/0.25mg/L)相比,其效力高 16 倍,与左氧氟沙星(MIC(50/90)为 1/1mg/L)和环丙沙星(MIC(50/90)为 1/2mg/L)相比,其活性高至少 128 倍。流感嗜血杆菌分离株对氨苄西林的耐药率为 21.9%-23.3%,但 JNJ-Q2(MIC(50/90)≤0.004/0.015mg/L)对莫西沙星(MIC(50/90)为 0.015/0.03mg/L)的活性至少高两倍,对卡他莫拉菌(MIC(90)为 0.015/0.015mg/L)也具有强大的活性。综上所述,与已用于治疗 CABP 病原体的其他市售氟喹诺酮类药物相比,JNJ-Q2 显示出更高的效力,因此有利于进一步的临床开发。

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