Cerebrospinal Pharmacokinetic Analysis and Pharmacodynamic Evaluation of Ceftriaxone in Pediatric Patients with Bacterial Meningitis

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Journal of Clinical Pharmacy and Therapeutics Pub Date : 2024-02-02 DOI:10.1155/2024/4684986
Tetsushu Onita, Kazuro Ikawa, Noriyuki Ishihara, Hiroki Tamaki, Takahisa Yano, Norifumi Morikawa, Kohji Naora
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Abstract

What Is Known? and Objective. Ceftriaxone has been widely used to treat bacterial meningitis in pediatric patients. Ceftriaxone dosing regimens of 80–120 mg/kg/day have been recommended for bacterial meningitis in pediatric patients, and the usual duration of therapy is 7–14 days. Although the target site for meningitis is cerebrospinal fluid (CSF), a CSF pharmacokinetic (PK) model in pediatric patients has not been reported. We aimed to develop a CSF PK model of ceftriaxone, using not only serum but also CSF concentration data, and to evaluate the appropriateness of dosing regimens for pediatric patients with bacterial meningitis. Methods. The population PK model was developed by simultaneously fitting serum and CSF data from pediatric patients described in nine published articles. Probabilities of attaining a pharmacodynamic target (100% T > MIC, 100% of time that drug concentrations above the minimum inhibitory concentration) in CSF were estimated for some dosing regimens. Results and Discussion. Twenty-four pediatric patients with meningitis were the subjects for PK modeling (0.52–13 years old, and 3.5–50 kg of body weight). Sixty-eight serum concentrations and 98 CSF samples were used to develop the CSF PK model. The CSF/serum concentration ratio at the same sampling time was 0.0628 ± 0.0689. Age was not a statistically significant covariate in the PK parameter. In the CSF PK model, 40–60 mg/kg q12 h achieved a target attainment probability >90% against causative bacteria for bacterial meningitis. However, 4-h infusion (rather than 0.5-h infusion) dosing regimens were required for efficacy against antimicrobial-resistant bacteria with high MICs. What Is New? and Conclusion. Ceftriaxone-dosing regimens with prolonged infusion times might be reasonably effective for treating antimicrobial-resistant pathogens in empiric therapy.

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细菌性脑膜炎儿科患者脑脊液药代动力学分析和头孢曲松药效学评估
已知信息和目标。头孢曲松已被广泛用于治疗儿童细菌性脑膜炎。头孢曲松被推荐用于治疗儿童细菌性脑膜炎,剂量为 80-120 毫克/千克/天,疗程通常为 7-14 天。虽然脑膜炎的目标部位是脑脊液(CSF),但尚未有关于儿科患者脑脊液药代动力学(PK)模型的报道。我们的目的是建立头孢曲松的 CSF PK 模型,不仅使用血清数据,还使用 CSF 浓度数据,并评估给药方案对细菌性脑膜炎儿科患者的适宜性。方法通过同时拟合九篇已发表文章中描述的儿科患者的血清和脑脊液数据,建立了群体 PK 模型。估计了某些给药方案在脑脊液中达到药效学目标(100% T > MIC,100%的时间药物浓度高于最小抑制浓度)的概率。结果与讨论。24 名患有脑膜炎的儿童患者是 PK 模型的研究对象(0.52-13 岁,体重 3.5-50 公斤)。68份血清浓度样本和98份脑脊液样本被用于建立脑脊液PK模型。同一采样时间的 CSF/血清浓度比为 0.0628 ± 0.0689。年龄在 PK 参数中不是一个具有统计学意义的协变量。在脑脊液 PK 模型中,40-60 毫克/千克 q12 小时对细菌性脑膜炎致病菌的达标概率大于 90%。然而,4小时输注(而不是0.5小时输注)的给药方案需要对MICs较高的耐抗菌细菌有效。有什么新发现?在经验疗法中,延长输注时间的头孢曲松给药方案可能对治疗耐抗菌性病原体相当有效。
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来源期刊
CiteScore
4.10
自引率
5.00%
发文量
226
审稿时长
6 months
期刊介绍: The Journal of Clinical Pharmacy and Therapeutics provides a forum for clinicians, pharmacists and pharmacologists to explore and report on issues of common interest. Reports and commentaries on current issues in medical and pharmaceutical practice are encouraged. Papers on evidence-based clinical practice and multidisciplinary collaborative work are particularly welcome. Regular sections in the journal include: editorials, commentaries, reviews (including systematic overviews and meta-analyses), original research and reports, and book reviews. Its scope embraces all aspects of clinical drug development and therapeutics, including: Rational therapeutics Evidence-based practice Safety, cost-effectiveness and clinical efficacy of drugs Drug interactions Clinical impact of drug formulations Pharmacogenetics Personalised, stratified and translational medicine Clinical pharmacokinetics.
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