Regen Rebecca B, Schuman Sarah S, Chhim Rebecca F, Arnold Sandra R, Lee Kelley R
J Pediatr Pharmacol Ther. 2019 Jul-Aug;24(4):312-319. doi: 10.5863/1551-6776-24.4.312.
Limited data exist regarding clinical outcomes of invasive methicillin-resistant Staphylococcus aureus (MRSA) infections in children treated with vancomycin. Treatment success in adults correlates best with an area under the curve/minimum inhibitory concentration (AUC/MIC) ratio ≥400. It is unknown if this relationship is useful in children.
Charts of children who received vancomycin ≥5 days for MRSA bacteremia with a steady state trough were reviewed. AUC/MIC ratios were estimated using 2 different vancomycin clearance equations. Vancomycin treatment failure was defined as persistent bacteremia ≥7 days, recurrent bacteremia within 30 days, or 30-day mortality.
There were 67 bacteremia episodes in 65 patients. Nine (13.4%) met failure criteria: persistent bacteremia (n = 6), recurrent bacteremia (n = 2), 30-day mortality (n = 1). There were no differences between patients receiving <60 mg/kg/day and ≥60 mg/kg/day of vancomycin in median trough (11.9 versus 12.3 mg/L, p = 0.1). Troughs did not correlate well with AUC/MIC ratios ( = 0.32 and 0.22). Patients receiving ≥60 mg/kg/day had greater probability of achieving ratios ≥400. There were no significant differences in median dose (p = 0.8), trough (p = 0.24), or AUC/MIC ratios (p = 0.07 and p = 0.6) between patients with treatment success and failure.
Treatment failure was lower than previously reported in children. AUC/MIC ratios ≥400 were frequently achieved but were not associated with treatment success, dose, or troughs. Prospective studies using standard definitions of vancomycin treatment failure are needed to understand treatment failure in children with MRSA bacteremia.
关于用万古霉素治疗的儿童侵袭性耐甲氧西林金黄色葡萄球菌(MRSA)感染的临床结局,现有数据有限。成人治疗成功与曲线下面积/最低抑菌浓度(AUC/MIC)比值≥400的相关性最佳。尚不清楚这种关系在儿童中是否有用。
回顾了因MRSA菌血症接受万古霉素治疗≥5天且有稳态谷浓度的儿童病历。使用2种不同的万古霉素清除率方程估算AUC/MIC比值。万古霉素治疗失败定义为持续性菌血症≥7天、30天内复发性菌血症或30天死亡率。
65例患者发生了67次菌血症发作。9例(13.4%)符合失败标准:持续性菌血症(n = 6)、复发性菌血症(n = 2)、30天死亡率(n = 1)。接受<60 mg/kg/天和≥60 mg/kg/天万古霉素的患者在中位谷浓度方面无差异(11.9对12.3 mg/L,p = 0.1)。谷浓度与AUC/MIC比值的相关性不佳(r = 0.32和0.22)。接受≥60 mg/kg/天的患者达到比值≥400的概率更高。治疗成功与失败的患者在中位剂量(p = 0.8)、谷浓度(p = 0.24)或AUC/MIC比值(p = 0.07和p = 0.6)方面无显著差异。
治疗失败率低于先前报道的儿童患者。经常达到AUC/MIC比值≥400,但与治疗成功、剂量或谷浓度无关。需要采用万古霉素治疗失败的标准定义进行前瞻性研究,以了解MRSA菌血症儿童患者的治疗失败情况。