肺炎球菌结合疫苗时代小儿社区获得性肺炎球菌肺炎的阿莫西林和青霉素 G 剂量。

IF 2.9 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Pharmacotherapy Pub Date : 2024-08-01 Epub Date: 2023-01-09 DOI:10.1002/phar.2756
Dustin Huynh, Norint Tung, Quang Dam, Tri Tran, Kristina G Hulten, Christopher J Harrison, Sheldon L Kaplan, Allison Nguyen, Tyler H Do, Amartya Setty, Jennifer Le
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引用次数: 0

摘要

背景:推荐使用肠外青霉素 G(PENG)和口服阿莫西林(AMOX)治疗小儿社区获得性肺炎(CAP)。肺炎链球菌是 CAP 最常见的病原体,根据最近的流行病学青霉素药敏数据,本研究旨在根据与当前药敏数据相关的人群药代动力学评估 PENG 和 AMOX 的最佳给药方案:使用 NONMEM v7.3,对 AMOX 15 毫克/千克/剂量,每 8 小时 PO 一次(标准剂量)、AMOX 45 毫克/千克/剂量,每 12 小时 PO 一次(高剂量)和 PENG 62,500 单位/千克/天,每 6 小时静脉注射一次进行蒙特卡罗模拟(N = 10,000)。测定了血清和上皮内衬液(ELF)达到目标的概率(PTA),使整个肺炎球菌群体在给药间隔的30%-50%时间内达到高于最小抑制浓度的游离药物浓度(%fT>MIC):2018年,根据临床和实验室标准协会(CLSI;MIC为2 mg/L)的断点,所有21株(100%)肺炎球菌分离株都对PENG和AMOX敏感,根据EUCAST(MIC为0.5 mg/L)的断点,21株中有15株(71%)对PENG和AMOX敏感。与 CLSI 相比,EUCAST 断点对所有抗生素方案的 PTA 值都更高。当血清中易感 MIC 为 50% fT>MIC 时,标准剂量 AMOX 可达到 >4% PTA(CLSI)和 >86% PTA(EUCAST);高剂量 AMOX 可达到 >73% PTA(CLSI)和 >99% PTA(EUCAST);而 PENG 可达到 0% PTA(采用 CLSI)和 100% PTA(采用 EUCAST)。根据国家药敏数据的频率分布,将每位患者的血清中 30%-50% fT>MIC 的浓度与 MIC 随机联系起来,标准剂量 AMOX、高剂量 AMOX 和 PENG 的 PTA 分别达到了 >71%、>93% 和 100%。在所有治疗方案中,ELF中的PTA始终低于血清中的PTA:结论:根据最近的耐药率,所评估的抗生素剂量可为小儿 CAP 提供适当的暴露,其依据是与肺炎球菌临床和微生物学成功预测相关的血清和 ELF 数据。治疗小儿 CAP 可能仍然需要大剂量 AMOX,尤其是在使用 CLSI 断点的情况下。持续监测耐药性至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Amoxicillin and penicillin G dosing in pediatric community-acquired pneumococcal pneumonia in the era of conjugate pneumococcal vaccines.

Background: Parenteral penicillin G (PENG) and oral amoxicillin (AMOX) are recommended as treatment for pediatric community-acquired pneumonia (CAP). With recent epidemiologic penicillin susceptibility data for Streptococcus pneumoniae, the most common etiology of CAP, the objective of this study was to evaluate optimal dosing regimens of PENG and AMOX based on population pharmacokinetics linked to current susceptibility data.

Methods: Using NONMEM v7.3, Monte Carlo simulations (N = 10,000) were conducted for AMOX 15 mg/kg/dose PO every 8 h (standard-dose), AMOX 45 mg/kg/dose PO every 12 h (high-dose), and PENG 62,500 units/kg/day IV every 6 h using six virtual subjects with ages spanning 3 months to 15 years old. The probability of target attainment (PTA) was determined for both serum and epithelial lining fluid (ELF) to achieve free drug concentrations above the minimum inhibitory concentration (%fT>MIC) across the population of pneumococci for 30%-50% of the dosing interval.

Results: In 2018, all 21 (100%) pneumococcal isolates were susceptible to both PENG and AMOX based on Clinical and Laboratory Standards Institute (CLSI; MIC at 2 mg/L) breakpoints, and 15 of 21 (71%) were susceptible based on EUCAST (MIC at 0.5 mg/L) breakpoints. As compared to CLSI, EUCAST breakpoints consistently achieved higher PTA for all antibiotic regimens. At 50% fT>MIC in the serum at the susceptible MICs, standard-dose AMOX achieved >4% PTA (CLSI) and >86% PTA (EUCAST); high-dose AMOX achieved >73% PTA (CLSI) and >99% PTA (EUCAST); and PENG achieved 0% PTA (using CLSI) and 100% PTA (using EUCAST). Standard-dose AMOX, high-dose AMOX, and PENG achieved >71%, >93%, and 100% PTA, respectively, in the serum at 30%-50% fT>MIC when each patient was stochastically linked to an MIC based on the frequency distribution of national susceptibility data. The PTA was consistently lower in ELF as compared with serum for all regimens.

Conclusion: Based on the recent rates of resistance, antibiotic doses evaluated provide appropriate exposure for pediatric CAP based on the serum and ELF data associated with predicted clinical and microbiologic success for pneumococcus. High-dose AMOX may still be required to treat pediatric CAP, especially if using CLSI breakpoints. Ongoing surveillance for resistance is essential.

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来源期刊
Pharmacotherapy
Pharmacotherapy 医学-药学
CiteScore
7.80
自引率
2.40%
发文量
93
审稿时长
4-8 weeks
期刊介绍: Pharmacotherapy is devoted to publication of original research articles on all aspects of human pharmacology and review articles on drugs and drug therapy. The Editors and Editorial Board invite original research reports on pharmacokinetic, bioavailability, and drug interaction studies, clinical trials, investigations of specific pharmacological properties of drugs, and related topics.
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