{"title":"头孢吡肟/恩美唑巴坦:微生物学、药代动力学、药效学和临床评估。","authors":"Christopher A Darlow, William Hope, Vineet Dubey","doi":"10.1080/17425255.2024.2427310","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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, <i>Acinetobacter</i> spp. and anaerobes. There is no completely reliable activity against carbapenem-resistant organisms.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>","PeriodicalId":94005,"journal":{"name":"Expert opinion on drug metabolism & toxicology","volume":" ","pages":"115-123"},"PeriodicalIF":0.0000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cefepime/Enmetazobactam: a microbiological, pharmacokinetic, pharmacodynamic, and clinical evaluation.\",\"authors\":\"Christopher A Darlow, William Hope, Vineet Dubey\",\"doi\":\"10.1080/17425255.2024.2427310\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>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, <i>Acinetobacter</i> spp. and anaerobes. There is no completely reliable activity against carbapenem-resistant organisms.</p><p><strong>Areas covered: </strong>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.</p><p><strong>Expert opinion: </strong>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.</p>\",\"PeriodicalId\":94005,\"journal\":{\"name\":\"Expert opinion on drug metabolism & toxicology\",\"volume\":\" \",\"pages\":\"115-123\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert opinion on drug metabolism & toxicology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1080/17425255.2024.2427310\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert opinion on drug metabolism & toxicology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1080/17425255.2024.2427310","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/10 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
简介头孢吡肟/恩美唑巴坦是一种新型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 的水解具有较强的抵抗力,而恩美唑巴坦对所有 Ambler A 类广谱β-内酰胺酶(ESBLs)均有抑制作用。因此,该组合对许多 ESBLs 的水解具有抗性。重要的广谱缺口包括 MRSA、肠球菌、醋酸杆菌属和厌氧菌。对碳青霉烯类耐药菌没有完全可靠的活性:我们通过对已发表的有关头孢吡肟/头孢美唑巴坦的文献进行回顾,介绍了头孢吡肟/头孢美唑巴坦的化学成分、药效学、药代动力学、毒性、药物间相互作用、临床疗效和目前的监管情况:头孢吡肟/恩美唑巴坦的主要潜在作用是作为一种碳青霉烯类备用药物,用于治疗由产ESBL肠杆菌引起的感染,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。鉴于其活性范围和药代动力学特性,头孢吡肟/恩美唑巴坦可能会用于治疗生殖道感染、腹腔感染和新生儿败血症。不过,在这些情况下使用前还需要进行更多的非临床和临床研究。
Cefepime/Enmetazobactam: a microbiological, pharmacokinetic, pharmacodynamic, and clinical evaluation.
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, Acinetobacter 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.