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头孢地尔在德国针对革兰氏阴性菌病原体的体外活性。

In vitro activity of cefiderocol against Gram-negative bacterial pathogens in Germany.

作者信息

Thelen Philipp, Henriksen Anne Santerre, Longshaw Christopher, Yamano Yoshinori, Caldwell Ben, Hamprecht Axel

机构信息

Institute for Medical Microbiology and Virology, University of Oldenburg and Klinikum Oldenburg, Oldenburg, Germany.

Medical Affairs Europe, Shionogi Europe, London, UK.

出版信息

J Glob Antimicrob Resist. 2022 Mar;28:12-17. doi: 10.1016/j.jgar.2021.10.029. Epub 2021 Dec 14.

Abstract

OBJECTIVES

Widespread antimicrobial resistance in Gram-negative bacteria (GNB), particularly carbapenem resistance, represents a major clinical challenge. Cefiderocol is a novel siderophore cephalosporin active against all carbapenemase classes.

METHODS

We evaluated the in vitro activity of cefiderocol and other antibacterial agents (ceftazidime/avibactam, ceftolozane/tazobactam, colistin and meropenem) against GNB isolates collected in Germany (2013-2018) as part of two multinational studies. Antimicrobial susceptibility testing was performed by broth microdilution. Minimum inhibitory concentrations were interpreted according to EUCAST breakpoints.

RESULTS

Cefiderocol had high activity against GNB isolates (N = 2298), encompassing both Enterobacterales (n = 1562) and non-fermenter species (n = 736), and maintained high activity against carbapenem-resistant strains (n = 211). The activity of cefiderocol against Enterobacterales was equivalent to that of ceftazidime/avibactam and colistin, while ceftolozane/tazobactam was somewhat less active. Against non-fermenter species, cefiderocol displayed equivalent activity to colistin; both of these agents were more active than ceftazidime/avibactam and ceftolozane/tazobactam. Colistin had similar activity to cefiderocol against the majority of species. These patterns of activity were echoed in carbapenem-resistant isolates. The high activity of cefiderocol was independent of infection site, whereas other antibacterial agents demonstrated slightly lower activity against isolates causing pneumonia compared with those from other key infection sites.

CONCLUSION

Cefiderocol exhibited consistently high in vitro activity against a variety of GNB isolates collected in Germany, including resistant phenotypes, across multiple infection sites. These data suggest that cefiderocol is an effective choice of antibacterial agent in patients with GNB infection, regardless of species and resistance phenotype to other agents.

摘要

目的

革兰氏阴性菌(GNB)中广泛存在的抗菌药物耐药性,尤其是碳青霉烯耐药性,是一项重大的临床挑战。头孢地尔是一种新型的铁载体头孢菌素,对所有碳青霉烯酶类别均有活性。

方法

作为两项跨国研究的一部分,我们评估了头孢地尔和其他抗菌药物(头孢他啶/阿维巴坦、头孢洛扎/他唑巴坦、黏菌素和美罗培南)对在德国收集的GNB分离株(2013 - 2018年)的体外活性。采用肉汤微量稀释法进行抗菌药物敏感性试验。最低抑菌浓度根据欧洲抗菌药物敏感性试验委员会(EUCAST)的断点进行判读。

结果

头孢地尔对GNB分离株(N = 2298)具有高活性,包括肠杆菌科细菌(n = 1562)和非发酵菌(n = 736),并对碳青霉烯耐药菌株(n = 211)保持高活性。头孢地尔对肠杆菌科细菌的活性与头孢他啶/阿维巴坦和黏菌素相当,而头孢洛扎/他唑巴坦的活性稍低。对于非发酵菌,头孢地尔与黏菌素表现出相当的活性;这两种药物均比头孢他啶/阿维巴坦和头孢洛扎/他唑巴坦更具活性。黏菌素对大多数菌种的活性与头孢地尔相似。这些活性模式在碳青霉烯耐药分离株中也有体现。头孢地尔的高活性与感染部位无关,而其他抗菌药物对引起肺炎的分离株的活性略低于来自其他关键感染部位的分离株。

结论

头孢地尔对在德国收集的多种GNB分离株,包括耐药表型,在多个感染部位均表现出持续的高体外活性。这些数据表明,无论菌种和对其他药物的耐药表型如何,头孢地尔都是GNB感染患者抗菌药物的有效选择。

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