Antimicrobial susceptibility of enterobacterales causing bloodstream infection in United States medical centres: comparison of aztreonam-avibactam with beta-lactams active against carbapenem-resistant enterobacterales.

IF 3.4 3区 医学 Q2 INFECTIOUS DISEASES BMC Infectious Diseases Pub Date : 2024-11-05 DOI:10.1186/s12879-024-10133-5
Helio S Sader, John H Kimbrough, Rodrigo E Mendes, Mariana Castanheira
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Abstract

Background: Bloodstream infection (BSI) is associated with poor outcomes especially when effective antimicrobial therapy and control of infection source are delayed. As the frequency of Enterobacterales producing metallo-β-lactamases (MBL) and/or OXA-48-like carbapenemases is increasing in some United States (US) medical centres, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers.

Objectives: To evaluate the antimicrobial susceptibility of Enterobacterales causing BSI in US medical centres and compare the activity of aztreonam-avibactam with ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and other antimicrobials used to treat BSI.

Methods: 4,802 Enterobacterales were consecutively collected (1/patient) from 72 US medical centres in 2020-2022 and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed concentration of 4 mg/L. A pharmacokinetic/pharmacodynamic susceptible breakpoint of ≤ 8 mg/L was applied for aztreonam-avibactam for comparison. Carbapenem-resistant Enterobacterales (CRE) isolates were tested for β-lactamase-encoding genes using Next-generation sequencing.

Results: Aztreonam-avibactam was highly active against Enterobacterales; only 2 isolates showed aztreonam-avibactam MICs > 8 mg/L: 1 meropenem-susceptible E. coli and 1 K. aerogenes (CRE). All carbapenemase producers and 98.0% of CRE were inhibited at an aztreonam-avibactam MIC of ≤ 8 mg/L. CRE susceptibility rates were 81.6% for ceftazidime-avibactam, 65.3% for meropenem-vaborbactam, 61.2% for imipenem-relebactam, and 87.8% for cefiderocol. Aztreonam-avibactam retained activity (MIC, ≤ 8 mg/L) against all (100.0%) meropenem-vaborbactam nonsusceptible (n = 17), 99.5% of imipenem-relebactam nonsusceptible (n = 206), and 90.0% of ceftazidime-avibactam nonsusceptible (n = 10) isolates. The most common carbapenemases were KPC-2/3 (57.1% of CREs), OXA-48-like (16.3%), and NDM (14.3%). A carbapenemase gene was not observed in 12.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were active against 100.0% of KPC producers, but ceftazidime-avibactam showed limited activity against MBL producers and meropenem-vaborbactam showed limited activity against OXA-48-like and MBL producers. The most active non-β-lactam comparators against CRE were gentamicin (49.0% susceptible) and amikacin (44.9% susceptible).

Conclusions: Aztreonam-avibactam demonstrated potent activity against a large collection of Enterobacterales isolated from patients with BSI in US hospitals, including CRE, MBL producers, and isolates resistant to recently approved β-lactamase inhibitor combinations.

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美国医疗中心中引起血流感染的肠杆菌的抗菌药敏感性:阿曲南-阿维菌素与对耐碳青霉烯类肠杆菌有效的β-内酰胺类药物的比较。
背景:血流感染(BSI)与不良预后有关,尤其是当有效的抗菌治疗和感染源控制被延误时。由于在美国一些医疗中心,产生金属-β-内酰胺酶(MBL)和/或 OXA-48 类碳青霉烯酶的肠杆菌的频率正在增加,因此迫切需要有效的抗菌药物来治疗由这些微生物引起的感染。氨曲南-阿维巴坦正在临床开发中,用于治疗革兰氏阴性菌(包括 MBL 生产者)引起的感染:评估美国医疗中心引起 BSI 的肠杆菌的抗菌药敏感性,并比较唑来南-阿维巴坦与头孢唑肟-阿维巴坦、美罗培南-瓦硼巴坦、亚胺培南-雷巴坦、头孢克肟和其他用于治疗 BSI 的抗菌药的活性。方法:2020-2022 年期间,从美国 72 个医疗中心连续收集了 4802 个肠杆菌(每个病人 1 个),并通过肉汤微量稀释法进行了药敏试验。氨曲南-阿维菌素与固定浓度为 4 毫克/升的阿维菌素一起进行了测试。为进行比较,唑来南-阿维菌素的药代动力学/药效学易感性断点为≤ 8 mg/L。使用新一代测序技术检测了耐碳青霉烯类肠杆菌(CRE)分离物中的β-内酰胺酶编码基因:结果:氨曲南-阿维菌素对肠杆菌具有很高的活性;只有 2 个分离株的氨曲南-阿维菌素 MIC > 8 mg/L:1 个是对美罗培南敏感的大肠杆菌,1 个是产气荚膜杆菌(CRE)。所有碳青霉烯酶生产者和 98.0% 的 CRE 在唑氯南-阿维菌素 MIC ≤ 8 mg/L 时均受到抑制。头孢唑肟-阿维巴坦对 CRE 的敏感率为 81.6%,美罗培南-瓦巴坦为 65.3%,亚胺培南-雷巴坦为 61.2%,头孢克肟为 87.8%。氨曲南-阿维巴坦对所有(100.0%)美罗培南-伐巴内酰胺不敏感菌株(n = 17)、99.5%亚胺培南-雷巴内酰胺不敏感菌株(n = 206)和 90.0%头孢他啶-阿维巴坦不敏感菌株(n = 10)均保持活性(MIC,≤ 8 mg/L)。最常见的碳青霉烯酶是 KPC-2/3(占 CRE 的 57.1%)、OXA-48-like(16.3%)和 NDM(14.3%)。12.3% 的 CREs 中未发现碳青霉烯酶基因。头孢唑肟-阿维巴坦和美罗培南-伐硼巴坦对 100.0% 的 KPC 生产者具有活性,但头孢唑肟-阿维巴坦对 MBL 生产者的活性有限,美罗培南-伐硼巴坦对 OXA-48 样和 MBL 生产者的活性有限。对 CRE 最有效的非β-内酰胺类比较药物是庆大霉素(49.0% 易感)和阿米卡星(44.9% 易感):结论:氨曲南-阿维菌素对从美国医院 BSI 患者中分离出的大量肠杆菌,包括 CRE、MBL 生产者和对最近批准的 β-内酰胺酶抑制剂复方制剂耐药的分离菌具有强效活性。
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来源期刊
BMC Infectious Diseases
BMC Infectious Diseases 医学-传染病学
CiteScore
6.50
自引率
0.00%
发文量
860
审稿时长
3.3 months
期刊介绍: BMC Infectious Diseases is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of infectious and sexually transmitted diseases in humans, as well as related molecular genetics, pathophysiology, and epidemiology.
期刊最新文献
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