Falagas Matthew E, Romanos Laura T, Kontogiannis Dimitrios S, Tsiara Katerina, Kakoullis Stylianos A
Alfa Institute of Biomedical Sciences (AIBS), 9 Neapoleos Street, Marousi, 151 23 Athens, Greece.
School of Medicine, European University Cyprus, 6 Diogenous Str., 2404 Nicosia, Cyprus.
Pathogens. 2025 Aug 6;14(8):777. doi: 10.3390/pathogens14080777.
Cefepime-enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination showing good activity against multidrug-resistant (MDR) Gram-negative bacteria producing a variety of β-lactamases. In this systematic review, we aimed to evaluate the available data on resistance to this drug. We performed a thorough search of four databases (Embase, PubMed, Scopus, and Web of Science), as well as backward citation searching, to identify studies containing data on resistance to cefepime-enmetazobactam. The data were extracted and analyzed according to the breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Food and Drug Administration (FDA), or the specific breakpoints reported by the authors of the respective studies. Analysis based on the type of lactamases produced by the isolates was also performed. Ten studies reported in vitro susceptibility testing and mechanisms of antimicrobial resistance. The total number of isolates was 15,408. The activity of cefepime-enmetazobactam against β-lactamase-producing isolates was variable. The resistance of the studied extended-spectrum β-lactamase (ESBL)-producing and ampicillin C β-lactamase (AmpC)-producing isolates was low (0-2.8% and 0%, respectively). The resistance was higher among oxacillinase-48 β-lactamase (OXA-48)-producing and carbapenemase (KPC)-producing isolates (3.4-13.2% and 36.7-57.8%, respectively). High resistance was noted among metallo-β- (MBL)-producing isolates (reaching 87.5% in one study), especially those producing New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM), which had the highest rates of resistance. The high activity of cefepime-enmetazobactam against Enterobacterales and selected lactose non-fermenting Gram-negative pathogens, including ESBL-producing and AmpC-producing isolates, makes it a potential carbapenem-sparing agent. The drug should be used after in vitro antimicrobial susceptibility testing in patients with infections caused by OXA-48, KPC, and MBL-producing isolates.
头孢吡肟-恩美他唑巴坦是一种新型的β-内酰胺类/β-内酰胺酶抑制剂组合，对产生多种β-内酰胺酶的多重耐药（MDR）革兰氏阴性菌显示出良好的活性。在本系统评价中，我们旨在评估关于该药物耐药性的现有数据。我们对四个数据库（Embase、PubMed、Scopus和Web of Science）进行了全面检索，并进行了反向引文检索，以识别包含头孢吡肟-恩美他唑巴坦耐药性数据的研究。根据欧洲抗菌药物敏感性试验委员会（EUCAST）和美国食品药品监督管理局（FDA）制定的断点，或各研究作者报告的特定断点，对数据进行提取和分析。还基于分离株产生的β-内酰胺酶类型进行了分析。十项研究报告了体外药敏试验和抗菌药物耐药机制。分离株总数为15408株。头孢吡肟-恩美他唑巴坦对产生β-内酰胺酶的分离株的活性各不相同。所研究的产超广谱β-内酰胺酶（ESBL）和产氨苄西林Cβ-内酰胺酶（AmpC）的分离株的耐药率较低（分别为0-2.8%和0%）。产奥沙西林酶-48β-内酰胺酶（OXA-48）和产碳青霉烯酶（KPC）的分离株中的耐药率较高（分别为3.4-13.2%和36.7-57.8%）。在产金属β-内酰胺酶（MBL）的分离株中观察到高耐药率（一项研究中达到87.5%），尤其是那些产生新德里金属β-内酰胺酶（NDM）和维罗纳整合子编码金属β-内酰胺酶（VIM）的分离株，其耐药率最高。头孢吡肟-恩美他唑巴坦对肠杆菌科细菌和选定的乳糖不发酵革兰氏阴性病原体（包括产ESBL和产AmpC的分离株）具有高活性，使其成为一种潜在的碳青霉烯类替代药物。对于由产OXA-48、KPC和MBL的分离株引起感染的患者，应在体外抗菌药物敏感性试验后使用该药物。
