使用头孢唑肟/阿维巴坦抗耐碳青霉烯类鲍曼不动杆菌的体外评估。

IF 3.7 3区 医学 Q2 INFECTIOUS DISEASES
{"title":"使用头孢唑肟/阿维巴坦抗耐碳青霉烯类鲍曼不动杆菌的体外评估。","authors":"","doi":"10.1016/j.jgar.2024.06.011","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) is a global concern as effective treatments are very limited. We previously used a modified susceptibility testing approach to predict growth suppression in carbapenem-resistant <em>Enterobacterales</em>, but there are uncertainties about the generalizability of the model. The objective of this study is to verify if a similar approach can be extended to CRAB.</p></div><div><h3>Method</h3><p>A clinical isolate of CRAB resistant to ceftazidime/avibactam (CAZ/AVI, MIC = 32/4 mg/L) was examined. CAZ susceptibility was determined using increasing concentrations of AVI (0–64 mg/L), and MIC reduction was characterized with a sigmoid inhibitory maximum effect (Emax) model. The effectiveness of CAZ/AVI was validated in a hollow fibre infection model (HFIM) over 72 hours, using simulated unbound serum / epithelial lining fluid (ELF) exposures of 2.5 g over 2 hours every 8 hours. Baseline inocula of approximately 5.5 log CFU/mL were examined.</p></div><div><h3>Results</h3><p>An AVI concentration-dependent reduction in CAZ MIC was observed (r<sup>2</sup> = 0.99). CAZ MIC was dramatically reduced from 512 mg/L (no AVI) to 32 mg/L (AVI = 4 mg/L), and further to 8 mg/L (AVI = 16 mg/L). Pharmacokinetic simulations were satisfactory in the HFIM (r<sup>2</sup> &gt; 0.96). Bacterial suppression was observed &gt;24 hours with the serum exposure, but not that from the ELF.</p></div><div><h3>Conclusion</h3><p>Using multiple AVI concentrations within the clinically relevant range, our susceptibility testing approach could have better insights of treatment outcome for infections caused by CRAB. This could potentially lead to effective intervention(s) overlooked by conventional susceptibility testing method. This case highlights the importance of site-specific drug exposures on determining treatment outcome.</p></div>","PeriodicalId":15936,"journal":{"name":"Journal of global antimicrobial resistance","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2213716524001218/pdfft?md5=8babafd4c28563b4fc240c4092c9fde4&pid=1-s2.0-S2213716524001218-main.pdf","citationCount":"0","resultStr":"{\"title\":\"In vitro evaluation of using ceftazidime/avibactam against carbapenem-resistant Acinetobacter baumannii\",\"authors\":\"\",\"doi\":\"10.1016/j.jgar.2024.06.011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>Carbapenem-resistant <em>Acinetobacter baumannii</em> (CRAB) is a global concern as effective treatments are very limited. We previously used a modified susceptibility testing approach to predict growth suppression in carbapenem-resistant <em>Enterobacterales</em>, but there are uncertainties about the generalizability of the model. The objective of this study is to verify if a similar approach can be extended to CRAB.</p></div><div><h3>Method</h3><p>A clinical isolate of CRAB resistant to ceftazidime/avibactam (CAZ/AVI, MIC = 32/4 mg/L) was examined. CAZ susceptibility was determined using increasing concentrations of AVI (0–64 mg/L), and MIC reduction was characterized with a sigmoid inhibitory maximum effect (Emax) model. The effectiveness of CAZ/AVI was validated in a hollow fibre infection model (HFIM) over 72 hours, using simulated unbound serum / epithelial lining fluid (ELF) exposures of 2.5 g over 2 hours every 8 hours. Baseline inocula of approximately 5.5 log CFU/mL were examined.</p></div><div><h3>Results</h3><p>An AVI concentration-dependent reduction in CAZ MIC was observed (r<sup>2</sup> = 0.99). CAZ MIC was dramatically reduced from 512 mg/L (no AVI) to 32 mg/L (AVI = 4 mg/L), and further to 8 mg/L (AVI = 16 mg/L). Pharmacokinetic simulations were satisfactory in the HFIM (r<sup>2</sup> &gt; 0.96). Bacterial suppression was observed &gt;24 hours with the serum exposure, but not that from the ELF.</p></div><div><h3>Conclusion</h3><p>Using multiple AVI concentrations within the clinically relevant range, our susceptibility testing approach could have better insights of treatment outcome for infections caused by CRAB. This could potentially lead to effective intervention(s) overlooked by conventional susceptibility testing method. This case highlights the importance of site-specific drug exposures on determining treatment outcome.</p></div>\",\"PeriodicalId\":15936,\"journal\":{\"name\":\"Journal of global antimicrobial resistance\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-07-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S2213716524001218/pdfft?md5=8babafd4c28563b4fc240c4092c9fde4&pid=1-s2.0-S2213716524001218-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of global antimicrobial resistance\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213716524001218\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of global antimicrobial resistance","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213716524001218","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0

摘要

目的:耐碳青霉烯类鲍曼不动杆菌(CRAB)是一个全球关注的问题,因为有效的治疗方法非常有限。我们以前曾使用一种改良的药敏试验方法来预测耐碳青霉烯类肠杆菌的生长抑制情况,但该模型的通用性还存在不确定性。本研究的目的是验证能否将类似方法扩展到 CRAB:方法:研究了对头孢他啶/阿维菌素(CAZ/AVI,MIC=32/4 mg/L)耐药的CRAB临床分离株。使用浓度不断升高的 AVI(0-64 mg/L)测定对 CAZ 的敏感性,MIC 值的降低采用乙叉抑制最大效应(Emax)模型进行表征。在中空纤维感染模型(HFIM)中,使用模拟非结合血清/上皮内衬液(ELF)暴露 2.5 克,每 8 小时暴露 2 小时,经过 72 小时验证了 CAZ/AVI 的有效性。检测的基线接种量约为 5.5 log CFU/mL:结果:观察到 AVI 浓度依赖性降低 CAZ MIC(r2=0.99)。头孢他啶的 MIC 从 512 mg/L(无 AVI)大幅降至 32 mg/L(AVI=4 mg/L),并进一步降至 8 mg/L(AVI=16 mg/L)。HFIM 中的药代动力学模拟结果令人满意(r2>0.96)。通过血清暴露观察到细菌抑制作用大于 24 小时,但 ELF 则没有:结论:使用临床相关范围内的多种 AVI 浓度,我们的药敏试验方法可以更好地了解 CRAB 引起的感染的治疗结果。这有可能导致传统药敏试验方法所忽视的有效干预。本病例强调了特定部位药物暴露对决定治疗结果的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
In vitro evaluation of using ceftazidime/avibactam against carbapenem-resistant Acinetobacter baumannii

Objective

Carbapenem-resistant Acinetobacter baumannii (CRAB) is a global concern as effective treatments are very limited. We previously used a modified susceptibility testing approach to predict growth suppression in carbapenem-resistant Enterobacterales, but there are uncertainties about the generalizability of the model. The objective of this study is to verify if a similar approach can be extended to CRAB.

Method

A clinical isolate of CRAB resistant to ceftazidime/avibactam (CAZ/AVI, MIC = 32/4 mg/L) was examined. CAZ susceptibility was determined using increasing concentrations of AVI (0–64 mg/L), and MIC reduction was characterized with a sigmoid inhibitory maximum effect (Emax) model. The effectiveness of CAZ/AVI was validated in a hollow fibre infection model (HFIM) over 72 hours, using simulated unbound serum / epithelial lining fluid (ELF) exposures of 2.5 g over 2 hours every 8 hours. Baseline inocula of approximately 5.5 log CFU/mL were examined.

Results

An AVI concentration-dependent reduction in CAZ MIC was observed (r2 = 0.99). CAZ MIC was dramatically reduced from 512 mg/L (no AVI) to 32 mg/L (AVI = 4 mg/L), and further to 8 mg/L (AVI = 16 mg/L). Pharmacokinetic simulations were satisfactory in the HFIM (r2 > 0.96). Bacterial suppression was observed >24 hours with the serum exposure, but not that from the ELF.

Conclusion

Using multiple AVI concentrations within the clinically relevant range, our susceptibility testing approach could have better insights of treatment outcome for infections caused by CRAB. This could potentially lead to effective intervention(s) overlooked by conventional susceptibility testing method. This case highlights the importance of site-specific drug exposures on determining treatment outcome.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Journal of global antimicrobial resistance
Journal of global antimicrobial resistance INFECTIOUS DISEASES-PHARMACOLOGY & PHARMACY
CiteScore
8.70
自引率
2.20%
发文量
285
审稿时长
34 weeks
期刊介绍: The Journal of Global Antimicrobial Resistance (JGAR) is a quarterly online journal run by an international Editorial Board that focuses on the global spread of antibiotic-resistant microbes. JGAR is a dedicated journal for all professionals working in research, health care, the environment and animal infection control, aiming to track the resistance threat worldwide and provides a single voice devoted to antimicrobial resistance (AMR). Featuring peer-reviewed and up to date research articles, reviews, short notes and hot topics JGAR covers the key topics related to antibacterial, antiviral, antifungal and antiparasitic resistance.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信