Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Infect Control Hosp Epidemiol. 2023 May;44(5):762-767. doi: 10.1017/ice.2022.161. Epub 2022 Jul 13.
We compared the activity of 8 novel β-lactam and tetracycline-derivative antibiotics against a cohort of clinical carbapenem-resistant Enterobacterales (CRE) isolates and investigated the incremental susceptibility benefit of the addition of an aminoglycoside, fluoroquinolone, or polymyxin to the β-lactam agents to assist with empiric antibiotic decision making.
A collection of consecutive CRE clinical isolates from unique patients at 3 US hospitals (2016-2021) was assembled. Broth microdilution was performed to obtain antimicrobial susceptibility testing results. Mechanisms of carbapenem resistance were investigated through short-read and long-read whole-genome sequencing.
Of the 603 CRE isolates, 276 (46%) were carbapenemase producing and 327 (54%) were non-carbapenemase producing, respectively. The organisms most frequently identified were (38%), complex (26%), and (16%). We obtained the following percent susceptibility to novel β-lactam agents: ceftazidime-avibactam (95%), meropenem-vaborbactam (92%), imipenem-relebactam (84%), and cefiderocol (92%). Aminoglycosides and the polymyxins provided greater incremental coverage as second agents, compared to fluoroquinolones. Amikacin and plazomicin exhibited the greatest additive value. Ceftazidime-avibactam, meropenem-vaborbactam, and cefiderocol were active against 94% of the 220 KPC-producing isolates. Cefiderocol was active against 83% of the 29 NDM-producing isolates. Ceftazidime-avibactam had 100% activity against the 9 OXA-48-like-producing isolates. Tigecycline had the highest activity compared to other tetracyclines against KPC, NDM, or OXA-48-like-producing isolates.
Selection among novel agents requires a nuanced understanding of the molecular epidemiology of CRE. This work provides insights into the comparative activity of novel agents and the additive value of a second antibiotic for empiric antibiotic decision making.
我们比较了 8 种新型β-内酰胺类和四环素衍生物抗生素对一组临床碳青霉烯类耐药肠杆菌科（CRE）分离株的活性，并研究了在β-内酰胺类抗生素中添加氨基糖苷类、氟喹诺酮类或多黏菌素类抗生素以协助经验性抗生素决策的增量药敏获益。
收集了来自美国 3 家医院（2016-2021 年）的独特患者的连续 CRE 临床分离株。通过肉汤微量稀释法获得抗菌药物敏感性测试结果。通过短读长和长读长全基因组测序研究碳青霉烯类耐药的机制。
在 603 株 CRE 分离株中，分别有 276 株（46%）产碳青霉烯酶和 327 株（54%）非产碳青霉烯酶。最常见的分离株分别为 （38%）、 复合体（26%）和 （16%）。我们获得了新型β-内酰胺类药物的以下药敏率：头孢他啶-阿维巴坦（95%）、美罗培南-维巴坦（92%）、亚胺培南-雷巴坦（84%）和头孢地尔（92%）。与氟喹诺酮类药物相比，氨基糖苷类和多黏菌素类药物作为二线药物提供了更大的增量覆盖范围。阿米卡星和黏菌素表现出最大的附加价值。头孢他啶-阿维巴坦、美罗培南-维巴坦和头孢地尔对 220 株产 KPC 株的活性均为 94%。头孢地尔对 29 株产 NDM 株的活性为 83%。头孢他啶-阿维巴坦对 9 株产 OXA-48 样株的活性为 100%。与产 KPC、NDM 或 OXA-48 样株相比，替加环素对其他四环素类药物具有最高的活性。
新型药物的选择需要对 CRE 的分子流行病学有细致的了解。这项工作提供了对新型药物比较活性的深入了解，以及在经验性抗生素决策中添加第二种抗生素的附加价值。
