Servicio de Microbiología Clínica e Instituto de Investigación Biomédica A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña, A Coruña, Spain.
Laboratorio de Referencia para tipado molecular y detección de mecanismos de resistencia a antimicrobianos de Andalucía (PIRASOA). Unidad de Gestión Clínica de Microbiología y Enfermedades Infecciosas, Hospital Universitario Virgen Macarena. Instituto de Biomedicina de Sevilla (IBIS), CSIC, Universidad de Sevilla, Seville, Spain.
Antimicrob Agents Chemother. 2024 Nov 6;68(11):e0092424. doi: 10.1128/aac.00924-24. Epub 2024 Oct 9.
We aimed to investigate the activity of and mechanisms of resistance to cefiderocol and innovative β-lactam/β-lactamase inhibitor combinations in a nationwide collection of double-carbapenemase-producing Enterobacterales. In all, 57 clinical isolates co-producing two carbapenemases collected from Spanish hospitals during the period 2017-2022 were analyzed. Minimum inhibitory concentration (MIC) values for ceftazidime, ceftazidime/avibactam, aztreonam, aztreonam/avibactam, aztreonam/nacubactam, cefiderocol, cefepime, cefepime/taniborbactam, cefepime/zidebactam, cefepime/nacubactam, imipenem, imipenem/relebactam, meropenem, meropenem/vaborbactam, meropenem/xeruborbactam, and meropenem/ANT3310 were determined by reference broth microdilution. Genetic drivers of resistance were analyzed by whole-genome sequencing (WGS). The collection covered nine carbapenemase associations: VIM + OXA-48 (21/57), NDM + OXA-48 (11/57), KPC + VIM (10/57), KPC + OXA-48 (6/57), IMP + OXA-48 (3/57), NDM + KPC (2/57), NDM + VIM (2/57), NDM + GES (1/57), and KPC + IMP (1/57). Ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam were the least active options. Aztreonam/avibactam and aztreonam/nacubactam were active against the whole collection and yielded MIC/MIC values of ≤0.25/0.5 mg/L and 1/2 mg/L, respectively. Cefepime/zidebactam (56/57 susceptible), meropenem/xeruborbactam (56/57 susceptible), cefepime/nacubactam (55/57 susceptible), and cefiderocol (53/57 susceptible) were also highly active, with MIC/MIC values ranging from ≤0.25-2 mg/L to 2-4 mg/L, respectively. Meropenem/ANT3310 (MIC/MIC = 0.5/≥64 mg/L; 47/57 susceptible) and cefepime/taniborbactam (MIC/MIC = 0.5/16 mg/L; 44/57 susceptible) also retained high levels of activity, although they were affected by NDM-type enzymes in combination with porin deficiency. Our findings highlight that cefiderocol and combinations of β-lactams and the novel β-lactamase inhibitors avibactam, nacubactam, taniborbactam, zidebactam, xeruborbactam, and ANT3310 show promising activity against double-carbapenemase-producing Enterobacterales.
我们旨在研究头孢地尔在全国范围内产双重碳青霉烯酶肠杆菌科中的活性及其耐药机制。在所有的 57 株临床分离株中，2017-2022 年间从西班牙医院共分离出 57 株同时产生两种碳青霉烯酶的临床分离株。采用参考肉汤微量稀释法测定头孢他啶、头孢他啶/阿维巴坦、氨曲南、氨曲南/阿维巴坦、氨曲南/那卢巴坦、头孢地尔、头孢吡肟、头孢吡肟/替加环素、头孢吡肟/齐多夫定、头孢吡肟/那卢巴坦、亚胺培南、雷巴坦/亚胺培南、美罗培南、沃巴坦/美罗培南、西罗巴坦/美罗培南和 ANT3310 的最小抑菌浓度（MIC）值。通过全基因组测序（WGS）分析耐药基因的驱动因素。该集合涵盖了九种碳青霉烯酶关联：VIM+OXA-48（21/57）、NDM+OXA-48（11/57）、KPC+VIM（10/57）、KPC+OXA-48（6/57）、IMP+OXA-48（3/57）、NDM+KPC（2/57）、NDM+VIM（2/57）、NDM+GES（1/57）和 KPC+IMP（1/57）。头孢他啶/阿维巴坦、亚胺培南/雷巴坦和美罗培南/沃巴坦的活性最低。氨曲南/阿维巴坦和氨曲南/那卢巴坦对整个集合均具有活性，MIC/MIC 值分别为≤0.25/0.5mg/L 和 1/2mg/L。头孢吡肟/齐多夫定（56/57 敏感）、美罗培南/西罗巴坦（56/57 敏感）、头孢吡肟/那卢巴坦（55/57 敏感）和头孢地尔（53/57 敏感）也具有高度的活性，MIC/MIC 值范围分别为≤0.25-2mg/L 至 2-4mg/L。美罗培南/ANT3310（MIC/MIC=0.5/≥64mg/L；47/57 敏感）和头孢吡肟/替加环素（MIC/MIC=0.5/16mg/L；44/57 敏感）也保留了较高的活性，尽管它们受到 NDM 型酶与孔蛋白缺乏结合的影响。我们的研究结果表明，头孢地尔和β-内酰胺类药物与新型β-内酰胺酶抑制剂阿维巴坦、那卢巴坦、替加环素、齐多夫定、西罗巴坦和 ANT3310 的组合对产双重碳青霉烯酶肠杆菌科具有良好的活性。
