Department of Pharmacy, National University of Singapore, Singapore
Department of Pharmacy, Singapore General Hospital, Singapore
Antimicrob Agents Chemother. 2018 Mar 27;62(4). doi: 10.1128/AAC.01647-17. Print 2018 Apr.
Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC/MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC/MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.
细菌败血症是新生儿发病率和死亡率的主要原因，尤其是涉及耐甲氧西林金黄色葡萄球菌（MRSA）的败血症。美国传染病学会的指南建议，当 MIC 值≤1mg/L 时，万古霉素 24 小时浓度-时间曲线下面积与 MIC 比值（AUC/MIC）>400 是预测治疗 MRSA 感染成功的最佳指标。在亚洲新生儿人群中，尚未研究稳态万古霉素谷浓度与 AUC 值（mg·h/L）之间的关系。我们在新加坡医院进行了回顾性图表审查，并在 5 年内收集了接受万古霉素治疗的新生儿的患者特征和治疗药物监测数据。从收集的数据中建立了一个单室群体药代动力学模型，对其进行了内部验证，然后用于评估稳态谷浓度与 AUC 之间的关系。还进行了蒙特卡罗模拟灵敏度分析。共纳入 76 例新生儿，共 429 个万古霉素浓度进行分析。胎龄（PMA）的中位数（四分位距）为 30 周（28 至 36 周），治疗开始时的体重中位数（四分位距）为 1043g（811 至 1919g）。万古霉素清除率由体重、PMA 和血清肌酐预测。对于 MIC 值≤1 的 MRSA 分离株，我们的主要发现是，预测达到 AUC/MIC>400 的最小稳态谷浓度范围为 8 至 8.9mg/L。稳态谷浓度在 15 至 20mg/L 范围内不太可能达到 AUC/MIC>400，而在 10 至 14.9mg/L 范围内可能更合适。
