Takumi Yukie, Tanaka Ryota, Iwao Motoshi, Tatsuta Ryosuke, Itoh Hiroki
Department of Clinical Pharmacy, Oita University Hospital, 1-1 Idaigaoka, Hasama-machi, Yufu, Oita 879-5593, Japan.
Antibiotics (Basel). 2025 Jun 2;14(6):570. doi: 10.3390/antibiotics14060570.
BACKGROUND/OBJECTIVES: The pharmacokinetics of vancomycin (VCM) in patients with febrile neutropenia (FN) are highly variable due to coexisting conditions such as systemic inflammatory response syndrome and augmented renal clearance. Upon hematopoietic recovery, VCM clearance (CLvcm) is expected to normalize, which contributes to intra-individual variability. This study aimed to investigate the factors contributing to intra-individual variability in CLvcm among pediatric patients with FN.
This retrospective, single-center study analyzed 33 pediatric patients (48 FN episodes) who met the inclusion criteria. CLvcm was estimated using Bayesian estimation based on the pediatric population pharmacokinetic model developed by Le et al., and standardized with allometrically scaled body weight. The change (Δ) in each clinical laboratory parameter or CLvcm was calculated as the difference between the values at the current and previous TDM within the same episode.
A total of 155 VCM TDM data points were analyzed. Intra-individual comparisons revealed that CLvcm decreased significantly in patients recovering from FN to a non-FN state ( = 18, = 0.0285). Further analysis of intra-individual variability revealed that Δ CLvcm correlated significantly with Δ hemoglobin, Δ C-reactive protein, and Δ maximum daily body temperature, with the strongest correlation observed for Δ maximum daily body temperature (rs = 0.325, = 0.001). Multivariate analysis confirmed Δ maximum daily body temperature as a significant factor influencing Δ CLvcm (B = 0.376, 95% CI: 0.074 to 0.678, = 0.015).
Maximum daily body temperature was identified as a factor influencing intra-individual variability in CLvcm in pediatric FN patients, particularly during the recovery process from FN to a non-FN state. The finding suggests that dose adjustment based on maximum daily body temperature may allow safe and effective VCM therapy in FN patients.
背景/目的：由于存在全身炎症反应综合征和肾清除率增加等共存情况，发热性中性粒细胞减少症（FN）患者中万古霉素（VCM）的药代动力学具有高度变异性。造血功能恢复后，VCM清除率（CLvcm）有望恢复正常，这导致个体内变异性。本研究旨在调查导致FN儿科患者CLvcm个体内变异性的因素。
这项回顾性单中心研究分析了33名符合纳入标准的儿科患者（48次FN发作）。CLvcm使用基于Le等人开发的儿科群体药代动力学模型的贝叶斯估计进行估计，并根据体表面积标准化体重进行标准化。计算每个临床实验室参数或CLvcm的变化（Δ），作为同一发作中当前和先前TDM值之间的差异。
共分析了155个VCM TDM数据点。个体内比较显示，从FN恢复到非FN状态的患者CLvcm显著降低（n = 18，P = 0.0285）。对个体内变异性的进一步分析显示，ΔCLvcm与Δ血红蛋白、ΔC反应蛋白和Δ最高每日体温显著相关，其中与Δ最高每日体温的相关性最强（rs = 0.325，P = 0.001）。多变量分析证实，最高每日体温是影响ΔCLvcm的重要因素（B = 0.376，95%CI：0.074至0.678，P = 0.015）。
最高每日体温被确定为影响儿科FN患者CLvcm个体内变异性的一个因素，特别是在从FN恢复到非FN状态的过程中。这一发现表明，根据最高每日体温进行剂量调整可能使FN患者获得安全有效的VCM治疗。
