From the Department of Cardiology and Cardiac Surgery, Pediatric Cardiac Intensive Care Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
The Center for Pediatric Pharmacotherapy, Pottstown, PA.
Pediatr Infect Dis J. 2019 May;38(5):484-489. doi: 10.1097/INF.0000000000002179.
This study aimed to explore inter-individual variability of cefoxitin trough levels, predictors of serum cefoxitin concentration and the probability of target attainment of drug levels above 4 mg/L after pediatric cardiac surgery.
Retrospective study on children scheduled for elective cardiac surgery and having cefoxitin trough levels available up to 24 hours postsurgery.
Overall, 68 children (9 neonates, 34 infants, 15 children below or equal to 10 years old and 10 patients above this age) were included. Of these, 16 surgeries were performed off cardiopulmonary bypass and 52 were performed on cardiopulmonary bypass. The free cefoxitin concentrations showed a median (interquartile range) concentration of 1.7 (0.6-4.2) mg/L. The range of cefoxitin concentrations showed a 150-fold and 340-fold variability at cardiac intensive care unit admission and after 24 hours, respectively. The pharmacodynamics (PD) targets of free cefoxitin at 100% of the dosing interval, considering Eucast breakpoints for Methicillin Sensitive Staphylococcus Aureus (4 mg/L) and E.Coli (8 mg/L), were obtained in 28% and 16% of patients, respectively. Patient weight (odds ratio, 0.7; 95% confidence interval, 0.62-0.92; P = 0.006) and serum creatinine concentrations (odds ratio, 25; 95% confidence interval, 18-36; P = 0.004) showed a significant relationship with the PD targets.
Cefoxitin trough concentrations vary significantly in the first 24 hours after pediatric cardiac surgery. Both serum creatinine and body weight showed independent associations with cefoxitin concentration. The PD target was not obtained in the vast majority of the explored population, regardless of the target bacteria.
本研究旨在探讨头孢西丁谷浓度的个体间变异性、血清头孢西丁浓度的预测因子以及小儿心脏手术后药物浓度超过 4mg/L 的目标达标概率。
这是一项回顾性研究，纳入了计划接受择期心脏手术且术后 24 小时内有头孢西丁谷浓度数据的儿童。
共有 68 名儿童（9 名新生儿、34 名婴儿、15 名 10 岁以下儿童和 10 名 10 岁以上儿童）入组。其中 16 例手术在体外循环下进行，52 例手术在体外循环下进行。游离头孢西丁浓度的中位数（四分位距）为 1.7（0.6-4.2）mg/L。心脏重症监护病房入院时和 24 小时后头孢西丁浓度范围分别为 150 倍和 340 倍。考虑到对甲氧西林敏感金黄色葡萄球菌（4mg/L）和大肠杆菌（8mg/L）的 Eucast 折点，在 100%给药间隔时游离头孢西丁的药效学（PD）目标在 28%和 16%的患者中得到了满足。患者体重（比值比，0.7；95%置信区间，0.62-0.92；P=0.006）和血清肌酐浓度（比值比，25；95%置信区间，18-36；P=0.004）与 PD 目标显著相关。
小儿心脏手术后的前 24 小时内，头孢西丁谷浓度变化显著。血清肌酐和体重均与头孢西丁浓度有独立关联。无论目标细菌如何，在绝大多数研究人群中都无法达到 PD 目标。
