Darlow Christopher A, Hope William, Dubey Vineet
Antimicrobial Pharmacodynamics and Therapeutics, University of Liverpool, Liverpool, UK.
Expert Opin Drug Metab Toxicol. 2025 Jan-Feb;21(2):115-123. doi: 10.1080/17425255.2024.2427310. Epub 2024 Nov 10.
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.
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.
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.
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。
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。
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。