Department of Pediatrics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
Department of Pediatrics, Dongguk University Ilsan Hospital, Dongguk University College of Medicine, Goyang, Republic of Korea.
PLoS One. 2021 Apr 1;16(4):e0247714. doi: 10.1371/journal.pone.0247714. eCollection 2021.
Optimal vancomycin exposure is important to minimize treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. We aimed to analyze the impact of initial vancomycin pharmacokinetic/pharmacodynamic (PK/PD) parameters, including the initial vancomycin C trough and the area under the curve (AUC)/minimal inhibitory concentration (MIC) on the outcomes of pediatric MRSA bacteremia. The study population consisted of hospitalized children aged between 2 months and 18 years with MRSA bacteremia, in whom C trough was measured at least one time within the time period of January 2010 to March 2018. Demographic profiles, underlying diseases, and clinical/microbiological outcomes were abstracted retrospectively. During the study period, 73 cases of MRSA bacteremia occurred in children with a median age of 12.4 months. Severe clinical outcomes leading to intensive care unit stay and/or use of mechanical ventilation occurred in 47.5% (35/73); all-cause 30-day mortality was 9.7% (7/72). The median dosage of vancomycin was 40.0 mg/kg/day. There was a weak linear relationship between C trough and the corresponding AUC/MIC (r = 0.235). ROC curves for achieving an AUC/MIC of 300 suggested that the initial C trough at 10 μg/mL could be used as a cut-off value with a sensitivity of 90.5% and a specificity of 44%. Although persistent bacteremia at 48-72 hours after vancomycin administration was observed more frequently when the initial C trough was < 10 μg/mL and initial AUC/MIC was < 300, initial AUC/MIC < 300 was the only risk factor associated with persistent bacteremia at 48-72 hours (adjusted OR 3.05; 95% CI, 1.07-8.68). Initial C trough and AUC/MIC were not associated with 30-day mortality. Although there was a weak relationship between C trough and AUC/MIC, initial AUC/MIC < 300 could be used as a predictor of persistent MRSA bacteremia at 48-72 hours. Further prospective data on optimal vancomycin dosing are necessary to improve clinical and microbiological outcomes in pediatric MRSA bacteremia.
优化万古霉素的暴露量对于降低耐甲氧西林金黄色葡萄球菌（MRSA）菌血症的治疗失败率非常重要。我们旨在分析初始万古霉素药代动力学/药效学（PK/PD）参数，包括初始万古霉素 C 谷值和 AUC/最小抑菌浓度（MIC），对儿科 MRSA 菌血症结局的影响。研究人群为 2010 年 1 月至 2018 年 3 月期间住院的年龄在 2 个月至 18 岁之间、至少有一次测量了 C 谷值的患有 MRSA 菌血症的儿童。回顾性提取人口统计学特征、基础疾病以及临床/微生物学结局。在研究期间，共有 73 例儿童发生 MRSA 菌血症，中位年龄为 12.4 个月。导致入住重症监护病房和/或使用机械通气的严重临床结局占 47.5%（35/73）；所有原因的 30 天死亡率为 9.7%（7/72）。万古霉素的中位剂量为 40.0mg/kg/天。C 谷值与相应 AUC/MIC 之间存在弱线性关系（r=0.235）。ROC 曲线表明，AUC/MIC 达到 300 时，初始 C 谷值为 10μg/mL 可作为截断值，其灵敏度为 90.5%，特异性为 44%。虽然在万古霉素治疗后 48-72 小时，当初始 C 谷值<10μg/mL 和初始 AUC/MIC<300 时，持续性菌血症更为常见，但初始 AUC/MIC<300 是与 48-72 小时持续性菌血症相关的唯一危险因素（调整 OR 3.05；95%CI，1.07-8.68）。初始 C 谷值和 AUC/MIC 与 30 天死亡率无关。尽管 C 谷值和 AUC/MIC 之间存在弱关系，但初始 AUC/MIC<300 可作为预测 48-72 小时持续性 MRSA 菌血症的指标。需要进一步前瞻性研究优化万古霉素剂量，以改善儿科 MRSA 菌血症的临床和微生物学结局。
