Allecra Therapeutics SAS, St Louis, France.
IHMA Europe Sàrl, Monthey, Switzerland.
J Glob Antimicrob Resist. 2021 Jun;25:93-101. doi: 10.1016/j.jgar.2021.02.031. Epub 2021 Mar 18.
This study aimed to investigate third-generation cephalosporin (3GC) resistance determinants [extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases and OXA-type β-lactamases] in contemporary clinical Enterobacterales isolates and to determine the in vitro activity of β-lactams and β-lactam/β-lactamase inhibitor combinations, including the investigational combination of cefepime and the novel β-lactamase inhibitor enmetazobactam.
Antibacterial susceptibility of 7168 clinical Enterobacterales isolates obtained between 2016-2018 from North America and Europe was determined according to CLSI guidelines. Phenotypic resistance to the 3GC ceftazidime (MIC ≥ 16 µg/mL) and/or ceftriaxone (MIC ≥ 4 µg/mL) but retaining susceptibility to meropenem (MIC ≤ 1 µg/mL) was determined. β-Lactamase genotyping was performed on clinical isolates with ceftazidime, ceftriaxone, cefepime or meropenem MIC ≥ 1 µg/mL.
Phenotypic resistance to 3GCs occurred in 17.5% of tested isolates, whereas 2.1% of isolates were resistant to the carbapenem meropenem. Within the 3GC-resistant subgroup, 60.1% (n = 752) of isolates encoded an ESBL, 25.6% (n = 321) encoded an AmpC-type β-lactamase and 0.9% (n = 11) encoded an OXA-type β-lactamase. Susceptibility of the subgroup to piperacillin/tazobactam (57.5%) and ceftolozane/tazobactam (71.3%) was <90% based on breakpoints established by the CLSI. Projected susceptibility to cefepime/enmetazobactam was 99.6% when applying the cefepime susceptible, dose-dependent breakpoint of 8 µg/mL. Against ESBL-producing isolates (n = 801) confirmed by genotyping, only susceptibility to meropenem (96.0%) and cefepime/enmetazobactam (99.9%) exceeded 90%.
This study describes the antibacterial activity of important therapies against contemporary 3GC-resistant clinical Enterobacterales isolates and supports the development of cefepime/enmetazobactam as a carbapenem-sparing option for ESBL-producing pathogens.
本研究旨在调查第三代头孢菌素（3GC）耐药决定因素[超广谱β-内酰胺酶（ESBLs）、AmpCβ-内酰胺酶和 OXA 型β-内酰胺酶]在当代临床肠杆菌科分离株中的情况，并确定β-内酰胺类药物和β-内酰胺/β-内酰胺酶抑制剂组合的体外活性，包括头孢吡肟和新型β-内酰胺酶抑制剂恩美曲妥珠单抗的研究组合。
根据 CLSI 指南，测定了 2016 年至 2018 年间北美和欧洲获得的 7168 例临床肠杆菌科分离株的抗菌药敏性。测定对 3GC 头孢他啶（MIC≥16μg/mL）和/或头孢曲松（MIC≥4μg/mL）耐药但对美罗培南（MIC≤1μg/mL）敏感的表型耐药性。对头孢他啶、头孢曲松、头孢吡肟或美罗培南 MIC≥1μg/mL 的临床分离株进行β-内酰胺酶基因分型。
在测试的分离株中，有 17.5%表现出对 3GC 的表型耐药性，而有 2.1%的分离株对碳青霉烯类美罗培南耐药。在 3GC 耐药亚组中，60.1%（n=752）的分离株编码 ESBL，25.6%（n=321）的分离株编码 AmpC 型β-内酰胺酶，0.9%（n=11）的分离株编码 OXA 型β-内酰胺酶。根据 CLSI 建立的折点，该亚组对哌拉西林/他唑巴坦（57.5%）和头孢洛扎/他唑巴坦（71.3%）的敏感性<90%。当应用头孢吡肟敏感、剂量依赖性的 8μg/mL 折点时，预测对头孢吡肟/恩美曲妥珠单抗的敏感性为 99.6%。对通过基因分型确认的产 ESBL 分离株（n=801）进行分析，只有对美罗培南（96.0%）和头孢吡肟/恩美曲妥珠单抗（99.9%）的敏感性超过 90%。
本研究描述了重要治疗药物对当代 3GC 耐药临床肠杆菌科分离株的抗菌活性，并支持头孢吡肟/恩美曲妥珠单抗作为产 ESBL 病原体碳青霉烯类药物的节约选择。
