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头孢吡肟/恩美他唑巴坦:微生物学、药代动力学、药效学及临床评价

Cefepime/Enmetazobactam: a microbiological, pharmacokinetic, pharmacodynamic, and clinical evaluation.

作者信息

Darlow Christopher A, Hope William, Dubey Vineet

机构信息

Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, UK.

出版信息

Expert Opin Drug Metab Toxicol. 2025 Jan-Feb;21(2):115-123. doi: 10.1080/17425255.2024.2427310. Epub 2024 Nov 10.

DOI:10.1080/17425255.2024.2427310
PMID:39508805
Abstract

INTRODUCTION

Cefepime/enmetazobactam is a novel β-lactam/β-lactamase inhibitor (BL-BLI) combination with broad Gram-positive and -negative activity. Cefepime is relatively resistant to hydrolysis by AmpC, and enmetazobactam inhibits all Ambler Class A extended spectrum β-lactamases (ESBLs). Hence, the combination is resistant to hydrolysis by many ESBLs. Important spectrum gaps are MRSA, enterococci, spp. and anaerobes. There is no completely reliable activity against carbapenem-resistant organisms.

AREAS COVERED

We describe the chemistry, pharmacodynamics, pharmacokinetics, toxicities, drug-drug interactions, clinical efficacy, and current regulatory position of cefepime/enmetazobactam, following a review of available published literature relating to cefepime/enmetazobactam.

EXPERT OPINION

The main potential role for cefepime/enmetazobactam is as a carbapenem-sparing agent for the treatment of infections caused by ESBL-producing Enterobacterales to prevent the use of carbapenems and to avoid the toxicities of non-β-lactam alternatives.There may be potential uses for cefepime/enmetazobactam for the treatment of reproductive tract infections, abdominal infections and neonatal sepsis, given the spectrum of activity and pharmacokinetic properties. However, additional non-clinical and clinical studies are required before use in these settings.

摘要

引言

头孢吡肟/恩美他唑巴坦是一种新型的β-内酰胺/β-内酰胺酶抑制剂(BL-BLI)组合,具有广泛的革兰氏阳性和阴性活性。头孢吡肟对AmpC介导的水解相对耐药,而恩美他唑巴坦可抑制所有安布勒A类超广谱β-内酰胺酶(ESBLs)。因此,该组合对许多ESBLs介导的水解具有耐药性。重要的抗菌谱空白包括耐甲氧西林金黄色葡萄球菌、肠球菌、某些菌属和厌氧菌。对耐碳青霉烯类微生物没有完全可靠的活性。

涵盖领域

在回顾了与头孢吡肟/恩美他唑巴坦相关的已发表文献后,我们描述了头孢吡肟/恩美他唑巴坦的化学、药效学、药代动力学、毒性、药物相互作用、临床疗效及当前的监管状况。

专家观点

头孢吡肟/恩美他唑巴坦的主要潜在作用是作为一种碳青霉烯类药物节省剂,用于治疗由产ESBL的肠杆菌科细菌引起的感染,以避免使用碳青霉烯类药物,并避免非β-内酰胺类替代药物的毒性。鉴于其抗菌谱活性和药代动力学特性,头孢吡肟/恩美他唑巴坦在治疗生殖道感染、腹部感染和新生儿败血症方面可能有潜在用途。然而,在这些情况下使用之前,还需要进行额外的非临床和临床研究。

相似文献

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Cefepime/Enmetazobactam: a microbiological, pharmacokinetic, pharmacodynamic, and clinical evaluation.头孢吡肟/恩美他唑巴坦:微生物学、药代动力学、药效学及临床评价
Expert Opin Drug Metab Toxicol. 2025 Jan-Feb;21(2):115-123. doi: 10.1080/17425255.2024.2427310. Epub 2024 Nov 10.
2
Cefepime-enmetazobactam: first approved cefepime-β- lactamase inhibitor combination for multi-drug resistant Enterobacterales.头孢吡肟-恩美他唑巴坦:首个获批用于多重耐药肠杆菌科细菌的头孢吡肟-β-内酰胺酶抑制剂复方制剂。
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In vitro activity of cefepime-enmetazobactam on carbapenem-resistant Gram negatives.头孢吡肟-恩美他唑巴坦对耐碳青霉烯革兰阴性菌的体外活性
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Evaluation of the activity of cefepime/enmetazobactam against Enterobacterales bacteria collected in Europe from 2019 to 2021, including third-generation cephalosporin-resistant isolates.评估头孢吡肟/恩他唑巴坦对 2019 年至 2021 年期间在欧洲收集的肠杆菌科细菌的活性,包括对第三代头孢菌素耐药的分离株。
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Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis: A Randomized Clinical Trial.头孢吡肟/恩他唑巴坦对比哌拉西林/他唑巴坦治疗复杂性尿路感染或急性肾盂肾炎患者的临床疗效和微生物学清除率:一项随机临床试验。
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Pharmacodynamics of Cefepime Combined with the Novel Extended-Spectrum-β-Lactamase (ESBL) Inhibitor Enmetazobactam for Murine Pneumonia Caused by ESBL-Producing .头孢吡肟联合新型扩展谱β-内酰胺酶(ESBL)抑制剂氨曲南治疗产 ESBL 肺炎克雷伯菌肺炎的药效学研究
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Development of Broth Microdilution MIC and Disk Diffusion Antimicrobial Susceptibility Test Quality Control Ranges for the Combination of Cefepime and the Novel β-Lactamase Inhibitor Enmetazobactam.头孢吡肟与新型β-内酰胺酶抑制剂恩他唑巴坦合剂的肉汤微量稀释 MIC 和纸片扩散药敏试验质控范围的制定。
J Clin Microbiol. 2019 Jul 26;57(8). doi: 10.1128/JCM.00607-19. Print 2019 Aug.

引用本文的文献

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Resistance of Gram-Negative Bacteria to Cefepime-Enmetazobactam: A Systematic Review.革兰氏阴性菌对头孢吡肟-恩美他唑巴坦的耐药性:一项系统评价
Pathogens. 2025 Aug 6;14(8):777. doi: 10.3390/pathogens14080777.
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A Practice Primer and Update on Anti-Bacterial Resistance.抗菌药物耐药性实践入门与更新
Mo Med. 2025 Jul-Aug;122(4):315-323.
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Game Changers: Blockbuster Small-Molecule Drugs Approved by the FDA in 2024.变革者:2024年获美国食品药品监督管理局批准的重磅小分子药物
Pharmaceuticals (Basel). 2025 May 15;18(5):729. doi: 10.3390/ph18050729.
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Cefepime-enmetazobactam: first approved cefepime-β- lactamase inhibitor combination for multi-drug resistant Enterobacterales.头孢吡肟-恩美他唑巴坦:首个获批用于多重耐药肠杆菌科细菌的头孢吡肟-β-内酰胺酶抑制剂复方制剂。
Future Microbiol. 2025 Mar;20(4):277-286. doi: 10.1080/17460913.2025.2468112. Epub 2025 Feb 26.