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英国一个大型中心产碳青霉烯酶肠杆菌科细菌的耐药谱:我们是否已经在失去头孢地尔?

Resistance profiles of carbapenemase-producing Enterobacterales in a large centre in England: are we already losing cefiderocol?

作者信息

Baltas Ioannis, Patel Trupti, Soares Ana Lima

机构信息

Department of Medical Microbiology, University College London Hospitals NHS Foundation Trust, London, UK.

Infection, Immunity & Inflammation Department, UCL Institute of Child Health, London, UK.

出版信息

J Antimicrob Chemother. 2025 Jan 3;80(1):59-67. doi: 10.1093/jac/dkae367.

DOI:10.1093/jac/dkae367
PMID:39504496
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11695913/
Abstract

BACKGROUND

Carbapenemase-producing Enterobacterales (CPE) pose difficult therapeutic challenges. We aimed to characterize antimicrobial resistance profiles of CPE in our centre.

METHODS

All non-duplicate CPE isolates between 1 August 2020 and 31 August 2023 in a large teaching trust in England were retrospectively studied. Cefiderocol antimicrobial susceptibility testing (AST) was performed using disc diffusion, ceftazidime/avibactam using disc diffusion and gradient diffusion, and ceftazidime/avibactam aztreonam synergy using the double disc diffusion method. EUCAST version 14.0 breakpoints were used.

RESULTS

A total of 158 CPE from 136 patients were isolated. Most patients were colonized with CPE, but only 16.9% had active infections. Thirty-day all-cause mortality was 10.3%, increasing to 13% for patients with infections and to 18.2% for bacteraemias. OXA-48 was the most prevalent carbapenemase (48.1%), followed by NDM (38%). All isolates exhibited MDR profiles, with high levels of resistance to meropenem (41.1%). Resistance to cefiderocol was found in 69.7% of NDM-producing isolates, with a further 18.2% in the area of technical uncertainty. Ceftazidime/avibactam and aztreonam synergy was seen in 87.5% of isolates, whereas colistin and fosfomycin susceptibility remained high (98.1% and 97.2%, respectively). All OXA-48-producing isolates were susceptible to ceftazidime/avibactam, and 15.3% were resistant to cefiderocol. No patients had been exposed to cefiderocol beforehand, whereas three had been exposed to ceftazidime/avibactam. The most common risk factor for CPE isolation was travel and receiving healthcare abroad, especially in Asia.

CONCLUSIONS

We found high rates of resistance to cefiderocol in CPE isolates without prior cefiderocol exposure. Our results prohibit empirical use of cefiderocol for the treatment of CPE infections in our setting.

摘要

背景

产碳青霉烯酶肠杆菌科细菌(CPE)带来了棘手的治疗挑战。我们旨在描述我院CPE的抗菌药物耐药谱。

方法

对2020年8月1日至2023年8月31日期间,英格兰一家大型教学信托机构中所有非重复的CPE分离株进行回顾性研究。采用纸片扩散法进行头孢地尔药敏试验(AST),采用纸片扩散法和梯度扩散法进行头孢他啶/阿维巴坦药敏试验,采用双纸片扩散法进行头孢他啶/阿维巴坦与氨曲南协同试验。使用欧盟CAST 14.0版的断点值。

结果

共分离出136例患者的158株CPE。大多数患者为CPE定植,但仅有16.9%发生了活动性感染。30天全因死亡率为10.3%,感染患者的死亡率升至13%,菌血症患者的死亡率升至18.2%。OXA-48是最常见的碳青霉烯酶(48.1%),其次是NDM(38%)。所有分离株均表现出多重耐药谱,对美罗培南的耐药率较高(41.1%)。在69.7%产NDM的分离株中发现对头孢地尔耐药,在技术不确定区域还有18.2%。87.5%的分离株中观察到头孢他啶/阿维巴坦与氨曲南协同,而对黏菌素和磷霉素的敏感性仍然很高(分别为98.1%和97.2%)。所有产OXA-48的分离株对头孢他啶/阿维巴坦敏感,15.3%对头孢地尔耐药。此前没有患者接触过头孢地尔,而有3名患者接触过头孢他啶/阿维巴坦。分离出CPE最常见的危险因素是出国旅行和接受国外医疗保健,尤其是在亚洲。

结论

我们发现未接触过头孢地尔的CPE分离株对头孢地尔的耐药率很高。我们的结果不支持在我们的环境中经验性使用头孢地尔治疗CPE感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd7/11695913/7ee96893fe49/dkae367f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd7/11695913/35fb6783cb6a/dkae367f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd7/11695913/d6f5fea83fc2/dkae367f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd7/11695913/7ee96893fe49/dkae367f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd7/11695913/35fb6783cb6a/dkae367f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd7/11695913/d6f5fea83fc2/dkae367f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/edd7/11695913/7ee96893fe49/dkae367f3.jpg

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