头孢克洛在体外和鼠腹膜炎模型中对产生 NDM-1 的大肠埃希菌的接种效果。

IF 3.9 2区 医学 Q1 INFECTIOUS DISEASES Journal of Antimicrobial Chemotherapy Pub Date : 2024-10-22 DOI:10.1093/jac/dkae368
Anne-Sophie Godron, Ariane Amoura, Claire Pistien, André Birgy, Sophie Magreault, Agnès B Jousset, Vincent Jullien, Agnès Lefort, Bruno Fantin, Imane El Meouche, Victoire de Lastours
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引用次数: 0

摘要

简介头孢羟氨苄(Cefiderocol)是一种嗜苷头孢菌素,在体外对产碳青霉烯酶肠杆菌(包括新德里金属-β-内酰胺酶(NDM-1))有活性。体外研究表明,细菌接种量的大小对其药效有很大影响,但其临床影响尚不清楚。在此,我们分析了头孢克洛在体外和小鼠腹膜炎模型中对大肠杆菌-NDM-1的接种效果:大肠杆菌 62-pTOPO 及其表达 NDM-1 的同源变体 62-pTOPO-NDM,均由临床菌株构建而成。测定了标准(105 cfu/mL)和高接种量(107 cfu/mL)下的 MIC 和杀菌动力学。在严重的小鼠腹膜炎模型中,对低接种量(106 cfu/mL)和高接种量(108 cfu/mL)的体内效果进行了评估。比较了存活率、器官消毒以及脾脏和腹腔液中的细菌计数:结果:在标准和高接种量下,62-pTOPO 和 62-pTOPO-NDM 的头孢菌素 MIC 分别为 0.008、2、2 和 1024 mg/L。在体外,62-pTOPO-NDM 在高接种量和高浓度 cefiderocol(16 毫克/升)条件下未达到杀菌活性。在体内,62-pTOPO-NDM 的存活率、器官消毒或细菌计数在低接种量和高接种量之间没有差异。对于 62-pTOPO,尽管高接种量的器官灭菌率较低,细菌计数较高,但存活率没有差异:结论:对于 62-pTOPO 和 62-pTOPO-NDM,在体外观察到头孢羟氨苄具有明显的接种量效应。然而,在体内高细菌接种量下,头孢羟氨苄的效果并没有降低。头孢羟氨苄的体外接种量效应可能没有临床意义。
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Inoculum effect of cefiderocol against NDM-1 producing Escherichia coli in vitro and in a murine model of peritonitis.

Introduction: Cefiderocol is a siderophore cephalosporin active in vitro against carbapenemase-producing Enterobacterales, including New Delhi metallo-β-lactamases (NDM-1). A significant impact of the size of bacterial inoculum on its efficacy has been described in vitro, the clinical impact of which is unclear. Here, we analyse the inoculum effect of cefiderocol against E. coli-NDM-1 in vitro and in a murine peritonitis model.

Materials and methods: Escherichia coli 62-pTOPO and its isogenic variant expressing NDM-1, 62-pTOPO-NDM, were constructed from a clinical strain. MICs and bactericidal kinetics were determined at standard (105 cfu/mL) and high inoculum (107 cfu/mL). The in vivo effect was assessed in a severe murine peritonitis model, comparing low (106 cfu/mL) and high (108 cfu/mL) inoculum. Survival rates, organ sterilization and bacterial counts in spleen and peritoneal fluid were compared.

Results: Cefiderocol MICs for 62-pTOPO and 62-pTOPO-NDM at standard and high inoculum were 0.008, 2, 2 and 1024 mg/L, respectively. Bactericidal activity was not achieved in vitro for 62-pTOPO-NDM at high inoculum with high cefiderocol concentrations (16 mg/L). In vivo, for 62-pTOPO-NDM, no difference was found in survival, organ sterilization or bacterial counts between low and high inoculum. For 62-pTOPO, no difference was observed in survival, despite less organ sterilization and higher bacterial counts in organs with the high inoculum.

Conclusion: A significant inoculum effect of cefiderocol was observed in vitro for 62-pTOPO and 62-pTOPO-NDM. However, the effectiveness of cefiderocol was not reduced in vivo with a high bacterial inoculum. In vitro inoculum effect of cefiderocol may not be clinically significant.

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来源期刊
CiteScore
9.20
自引率
5.80%
发文量
423
审稿时长
2-4 weeks
期刊介绍: The Journal publishes articles that further knowledge and advance the science and application of antimicrobial chemotherapy with antibiotics and antifungal, antiviral and antiprotozoal agents. The Journal publishes primarily in human medicine, and articles in veterinary medicine likely to have an impact on global health.
期刊最新文献
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