Pharmacokinetic/pharmacodynamic analysis of tedizolid phosphate against Staphylococcus aureus and Streptococcus pneumoniae in children, adolescents, and adults by Monte Carlo simulation

IF 3.7 3区医学 Q2 INFECTIOUS DISEASES

Journal of global antimicrobial resistance Pub Date : 2025-01-01 DOI:10.1016/j.jgar.2024.11.011

Xiao-Chen Wei , Ming-Feng Zhao , Hai-Rong Lv , Xia Xiao

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引用次数: 0

Abstract

Objective

The objective of this study was to investigate the cumulative fraction of response of various dosage regimens of tedizolid phosphate against Staphylococcus aureus and Streptococcus pneumoniae in children, adolescents, and adults.

Methods

Monte Carlo simulations were performed using previously published pharmacokinetic parameters and pharmacodynamic data to evaluate the efficacy of the simulated dosage strategies in terms of area under the concentration-time curve/minimum inhibitory concentration targets of tedizolid.

Results

According to the results of the Monte Carlo simulations, currently approved dosage regimens of tedizolid phosphate were effective in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) caused by methicillin-susceptible S. aureus and methicillin-resistant S. aureus (MRSA) including vancomycin-intermediate, heterogeneous vancomycin-intermediate, and daptomycin-non-susceptible MRSA in adult and paediatric patients aged 12 y and older. High-dose regimens of tedizolid phosphate should be the preferred option to optimize efficacy against ABSSSIs caused by linezolid-resistant MRSA, particularly chloramphenicol-florfenicol resistance-mediated isolates. The dosage regimens of 3 and 4 mg/kg/d of tedizolid phosphate were appropriate to treat ABSSSIs caused by methicillin-susceptible S. aureus and MRSA in children aged 2–6 and 6–12 y, respectively. Approved dosage regimens of tedizolid phosphate for patients older than 12 y may be sufficient against S. pneumoniae pneumonia but insufficient for S. aureus pneumonia. For neutropenic patients, almost all the simulated regimens of tedizolid phosphate were ineffective against S. aureus and S. pneumoniae.

Conclusions

These pharmacokinetics/pharmacodynamics-based simulations rationalize and optimize the dosage regimens of tedizolid phosphate against S. aureus and S. pneumoniae in children, adolescents, and adults.

Abstract Image

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通过蒙特卡罗模拟分析磷酸地唑脂对儿童、青少年和成人金黄色葡萄球菌和肺炎链球菌的药代动力学/药效学分析。

本研究的目的是调查在儿童、青少年和成人中，磷酸泰德唑胺不同剂量方案对金黄色葡萄球菌和肺炎链球菌的累积反应分数。使用先前发表的药代动力学参数和药效学数据进行蒙特卡洛模拟（mcs），以浓度-时间曲线下面积/泰德唑胺最小抑制浓度目标来评估模拟剂量策略的有效性。根据mcs的结果，目前批准的tedizolid phosphate剂量方案可有效治疗由甲氧西林敏感金黄色葡萄球菌（MSSA）和耐甲氧西林金黄色葡萄球菌（MRSA）引起的急性细菌性皮肤和皮肤结构感染（ABSSSIs），包括万古霉素中间体、异种万古霉素中间体和达托霉素非敏感MRSA的成人和12岁及以上儿童患者。然而，对于利奈唑胺耐药MRSA（尤其是cfr介导的分离株）引起的absssi，高剂量磷酸泰德唑胺应该是最佳的治疗方案。此外，2 ~ 6岁和6 ~ 12岁儿童分别以3 mg/kg/d和4 mg/kg/d的剂量方案治疗由MSSA和MRSA引起的ABSSSIs是合适的。此外，批准的用于12岁以上患者的磷酸泰德唑胺剂量方案可能足以对抗肺炎链球菌肺炎，但不足以对抗金黄色葡萄球菌肺炎。对于嗜中性粒细胞减少的患者，几乎所有的磷酸泰德唑脂模拟方案对金黄色葡萄球菌和肺炎链球菌无效。这些基于药代动力学/药效学的模拟合理化和优化了磷酸地唑酯在儿童、青少年和成人中抗金黄色葡萄球菌和肺炎链球菌的给药方案。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.