Tseng Yu-Ju, Tai Chih-Hsun, Chen Guan-Yuan, Chen Yen-Lin, Ku Shih-Chi, Pai Tsung-Yu, Wu Chien-Chih
Department of Pharmacy, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan.
School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.
Ther Adv Drug Saf. 2025 Feb 19;16:20420986251320414. doi: 10.1177/20420986251320414. eCollection 2025.
Patients with low body weight (LBW) often exhibit altered pharmacokinetics (PK) in renal clearance and total body water. These changes complicate β-lactam antibiotic dosing, potentially resulting in suboptimal efficacy or increased toxicity.
To evaluate the attainment of PK/pharmacodynamic (PD) targets, the prevalence of subtherapeutic and supratherapeutic concentrations, and the incidence of neurotoxicity among LBW patients treated with piperacillin/tazobactam (TZP), cefepime (FEP), and meropenem (MEM).
A prospective observational study conducted at a tertiary hospital from January 2020 to December 2022.
Adult patients with a body mass index ⩽18.5 kg/m who received TZP, FEP, or MEM were included. Trough serum concentrations were analyzed for PK/PD targets: 100% time above minimum inhibitory concentration (100% fT > MIC) and 100% time above four times MIC (100% fT > 4MIC). Neurotoxicity was assessed using standardized criteria. Statistical analyses identified factors associated with concentration variability and adverse outcomes.
Seventy-two patients were included: 29 received TZP, 23 FEP, and 20 MEM. Achievement of the 100% fT > MIC target was comparable across all antibiotics (~70%), but 100% fT > 4 MIC attainment was significantly higher for FEP (47.8%) than for TZP (10.3%) and MEM (30%) ( = 0.01). Supratherapeutic concentrations were observed in 34.8% of FEP users compared to 3.4% and 5% for TZP and MEM, respectively ( = 0.002). Neurotoxicity occurred in 13% of FEP patients but was not reported in TZP or MEM groups ( = 0.04). Subtherapeutic concentrations were noted in approximately 30% of patients across all groups.
PK changes complicate β-lactam antibiotic dosing, resulting in frequent failure to achieve PK/PD targets. FEP demonstrated a particularly high risk of supratherapeutic concentrations and neurotoxicity. Therapeutic drug monitoring is crucial to optimize dosing and improve safety in this population.
低体重（LBW）患者的肾脏清除率和总体液量的药代动力学（PK）常发生改变。这些变化使β-内酰胺类抗生素的给药复杂化，可能导致疗效欠佳或毒性增加。
评估接受哌拉西林/他唑巴坦（TZP）、头孢吡肟（FEP）和美罗培南（MEM）治疗的低体重患者中PK/药效学（PD）目标的达成情况、亚治疗浓度和超治疗浓度的发生率以及神经毒性的发生率。
2020年1月至2022年12月在一家三级医院进行的前瞻性观察性研究。
纳入体重指数≤18.5kg/m²且接受TZP、FEP或MEM治疗的成年患者。分析谷血清浓度以确定PK/PD目标：高于最低抑菌浓度的时间百分比（100% fT＞MIC）和高于四倍MIC的时间百分比（100% fT＞4MIC）。使用标准化标准评估神经毒性。统计分析确定与浓度变异性和不良结局相关的因素。
共纳入72例患者：29例接受TZP治疗，23例接受FEP治疗，20例接受MEM治疗。所有抗生素实现100% fT＞MIC目标的情况相近（约70%），但FEP实现100% fT＞4MIC的比例（47.8%）显著高于TZP（10.3%）和MEM（30%）（P = 0.01）。FEP使用者中超治疗浓度的发生率为34.8%，而TZP和MEM使用者分别为3.4%和5%（P = 0.002）。13%的FEP患者发生神经毒性，但TZP或MEM组未报告（P = 0.04）。所有组中约30%的患者出现亚治疗浓度。
PK变化使β-内酰胺类抗生素给药复杂化，导致经常无法实现PK/PD目标。FEP显示出超治疗浓度和神经毒性的特别高风险。治疗药物监测对于优化该人群的给药和提高安全性至关重要。
