Impact of Continuous Infusion Meropenem PK/PD Target Attainment on C-Reactive Protein Dynamics in Critically Ill Patients With Documented Gram-Negative Hospital-Acquired or Ventilator-Associated Pneumonia.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY Clinical Pharmacokinetics Pub Date : 2024-10-25 DOI:10.1007/s40262-024-01436-6
Carla Troisi, Pier Giorgio Cojutti, Matteo Rinaldi, Tommaso Tonetti, Antonio Siniscalchi, Coen van Hasselt, Pierluigi Viale, Federico Pea
{"title":"Impact of Continuous Infusion Meropenem PK/PD Target Attainment on C-Reactive Protein Dynamics in Critically Ill Patients With Documented Gram-Negative Hospital-Acquired or Ventilator-Associated Pneumonia.","authors":"Carla Troisi, Pier Giorgio Cojutti, Matteo Rinaldi, Tommaso Tonetti, Antonio Siniscalchi, Coen van Hasselt, Pierluigi Viale, Federico Pea","doi":"10.1007/s40262-024-01436-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of antibiotics including C-reactive protein (C-RP) dynamics could be helpful in predicting the efficacy of antimicrobials. We developed a PK/PD model for assessing the impact of continuous infusion (CI) meropenem PK/PD target attainment on C-RP dynamics in critically ill patients with documented Gram-negative hospital- (HAP) or ventilator-acquired pneumonia (VAP).</p><p><strong>Methods: </strong>Patients were grouped according to the type of antibiotic treatment received [meropenem monotherapy; meropenem plus empirical anti-MRSA (methicillin-resistant Staphylococcus aureus) therapy; meropenem in combination with another anti-Gram-negative active agent; meropenem plus a targeted anti-MRSA therapy]. A one-compartment population PK model of CI meropenem was developed by including all patients. A full C-RP production inhibition model was developed for fitting the PD data by including only patients receiving meropenem monotherapy or meropenem plus empirical anti-MRSA therapy. Monte Carlo simulations explored the relationship between the type of PK/PD target attainment of CI meropenem, defined as optimal (steady-state plasma concentration [C<sub>ss</sub>] to minimum inhibitory concentration [MIC] ratio = 4-8), quasi-optimal (C<sub>ss</sub>/MIC = 1-4) and sub-optimal (C<sub>ss</sub>/MIC < 1) and the magnitude of C-RP production inhibition over time.</p><p><strong>Results: </strong>A total of 64 patients providing 211 meropenem concentrations were included in the PK analysis, whereas 47 patients providing 328 C-RP data were included in the PD model. Simulations showed that optimal PK/PD target attainment was associated with the highest and most rapid C-RP production inhibition (44% and 56% at days 2 and 4, respectively). Conversely, sub-optimal PK/PD target attainment was shown to be almost ineffective (< 5% at day 4 and < 10% at day 10).</p><p><strong>Conclusion: </strong>Our PK/PD model predicted that attaining optimal PK/PD target with CI meropenem may grant prompt and intense C-RP decrease among critically ill patients receiving targeted monotherapy for Gram-negative HAP/VAP, thus anticipating efficacy.</p>","PeriodicalId":10405,"journal":{"name":"Clinical Pharmacokinetics","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Pharmacokinetics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40262-024-01436-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0

Abstract

Background and objective: Population pharmacokinetic/pharmacodynamic (PK/PD) modelling of antibiotics including C-reactive protein (C-RP) dynamics could be helpful in predicting the efficacy of antimicrobials. We developed a PK/PD model for assessing the impact of continuous infusion (CI) meropenem PK/PD target attainment on C-RP dynamics in critically ill patients with documented Gram-negative hospital- (HAP) or ventilator-acquired pneumonia (VAP).

Methods: Patients were grouped according to the type of antibiotic treatment received [meropenem monotherapy; meropenem plus empirical anti-MRSA (methicillin-resistant Staphylococcus aureus) therapy; meropenem in combination with another anti-Gram-negative active agent; meropenem plus a targeted anti-MRSA therapy]. A one-compartment population PK model of CI meropenem was developed by including all patients. A full C-RP production inhibition model was developed for fitting the PD data by including only patients receiving meropenem monotherapy or meropenem plus empirical anti-MRSA therapy. Monte Carlo simulations explored the relationship between the type of PK/PD target attainment of CI meropenem, defined as optimal (steady-state plasma concentration [Css] to minimum inhibitory concentration [MIC] ratio = 4-8), quasi-optimal (Css/MIC = 1-4) and sub-optimal (Css/MIC < 1) and the magnitude of C-RP production inhibition over time.

Results: A total of 64 patients providing 211 meropenem concentrations were included in the PK analysis, whereas 47 patients providing 328 C-RP data were included in the PD model. Simulations showed that optimal PK/PD target attainment was associated with the highest and most rapid C-RP production inhibition (44% and 56% at days 2 and 4, respectively). Conversely, sub-optimal PK/PD target attainment was shown to be almost ineffective (< 5% at day 4 and < 10% at day 10).

Conclusion: Our PK/PD model predicted that attaining optimal PK/PD target with CI meropenem may grant prompt and intense C-RP decrease among critically ill patients receiving targeted monotherapy for Gram-negative HAP/VAP, thus anticipating efficacy.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
持续输注美罗培南 PK/PD 达标对确诊为革兰氏阴性医院获得性肺炎或呼吸机相关肺炎重症患者 C 反应蛋白动态变化的影响
背景和目的:抗生素的群体药代动力学/药效学(PK/PD)模型包括C-反应蛋白(C-RP)动态,有助于预测抗菌药物的疗效。我们建立了一个PK/PD模型,用于评估连续输注(CI)美罗培南PK/PD目标的实现对有记录的革兰氏阴性医院性肺炎(HAP)或呼吸机获得性肺炎(VAP)重症患者C-RP动态的影响:根据患者接受的抗生素治疗类型进行分组[美罗培南单药治疗;美罗培南加经验性抗MRSA(耐甲氧西林金黄色葡萄球菌)治疗;美罗培南与另一种抗革兰氏阴性菌活性药物联合治疗;美罗培南加抗MRSA靶向治疗]。通过纳入所有患者,建立了 CI 美罗培南的单室群体 PK 模型。仅将接受美罗培南单药治疗或美罗培南加经验性抗 MRSA 治疗的患者纳入其中,建立了一个完整的 C-RP 生产抑制模型,以拟合 PD 数据。蒙特卡洛模拟探讨了CI美罗培南PK/PD目标实现类型之间的关系,定义为最佳(稳态血浆浓度[Css]与最小抑菌浓度[MIC]之比=4-8)、准最佳(Css/MIC=1-4)和次最佳(Css/MIC结果):共有 64 名患者提供了 211 个美罗培南浓度数据被纳入 PK 分析,47 名患者提供了 328 个 C-RP 数据被纳入 PD 模型。模拟结果显示,达到最佳 PK/PD 目标与最高和最快速的 C-RP 生成抑制有关(第 2 天和第 4 天分别为 44% 和 56%)。相反,次优的 PK/PD 目标实现则几乎没有效果(结论:我们的 PK/PD 模型预测,PK/PD 目标实现与 C-RP 生成抑制率最高、最迅速(第 2 天和第 4 天分别为 44% 和 56%)相关:我们的 PK/PD 模型预测,在接受革兰氏阴性 HAP/VAP 单药靶向治疗的重症患者中,使用 CI 美罗培南达到最佳 PK/PD 目标可使 C-RP 迅速而强烈地下降,从而达到预期疗效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
8.80
自引率
4.40%
发文量
86
审稿时长
6-12 weeks
期刊介绍: Clinical Pharmacokinetics promotes the continuing development of clinical pharmacokinetics and pharmacodynamics for the improvement of drug therapy, and for furthering postgraduate education in clinical pharmacology and therapeutics. Pharmacokinetics, the study of drug disposition in the body, is an integral part of drug development and rational use. Knowledge and application of pharmacokinetic principles leads to accelerated drug development, cost effective drug use and a reduced frequency of adverse effects and drug interactions.
期刊最新文献
Understanding Voriconazole Metabolism: A Middle-Out Physiologically-Based Pharmacokinetic Modelling Framework Integrating In Vitro and Clinical Insights. Clinical Pharmacology of Asciminib: A Review. Changes in Plasma Clearance of CYP450 Probe Drugs May Not be Specific for Altered In Vivo Enzyme Activity Under (Patho)Physiological Conditions: How to Interpret Findings of Probe Cocktail Studies. Population Pharmacokinetic Modelling of Norepinephrine in Healthy Volunteers Prior to and During General Anesthesia. Impact of Continuous Infusion Meropenem PK/PD Target Attainment on C-Reactive Protein Dynamics in Critically Ill Patients With Documented Gram-Negative Hospital-Acquired or Ventilator-Associated Pneumonia.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1