Bhatt-Mehta V, Schumacher R E, Faix R G, Leady M, Brenner T
Department of Pharmacy and the College of Pharmacy, University of Michigan Health Systems, Ann Arbor, Michigan 48109-0254, USA.
Pediatrics. 1999 Apr;103(4):e48. doi: 10.1542/peds.103.4.e48.
The purpose of this study was to compare the incidence of nephrotoxicity, defined as doubling of baseline serum creatinine concentration, in newborn infants with peak vancomycin serum concentrations </=40 microg/mL at steady state to infants with peak vancomycin serum concentrations >40 microg/mL. A secondary objective was to correlate concomitant disease states and potentially nephrotoxic drug therapy with rises in serum creatinine in vancomycin recipients.
Newborn infants with culture-proven Staphylococcus aureus or coagulase-negative staphylococcal septicemia who received vancomycin therapy for >3 days between 1985 and 1995 were identified from an existing database and a review of medical record. All 69 patients included in the study had serial serum creatinine determinations, including a baseline value within 48 hours of starting treatment with vancomycin, and serum vancomycin concentrations determined after at least three doses, with peak and trough concentrations determined 1 hour after a 60-minute infusion and 15 to 30 minutes before a dose, respectively. Infants with congenital renal or cardiac anomalies were excluded. Demographic characteristics, vancomycin dosing regimen, serum vancomycin concentrations and sample times, concomitant drug therapy, and disease states were recorded. Patients were divided into group A (peak vancomycin concentration </=40 microg/mL) and group B (peak vancomycin concentration >40 microg/mL). The change in serum creatinine concentration between the start and end of vancomycin therapy was determined. Nephrotoxicity was identified if serum creatinine doubled at any time from the start to the end of vancomycin therapy. Alternative definitions of nephrotoxicity (any rise in serum creatinine to >0.6 mg/dL or new abnormalities of urine sediment) were used in additional analyses.
A total of 69 evaluable patients (gestational age, 28.9 +/- 3.0 weeks; birth weight, 1219 +/- 516 g) were identified, 61 in group A and 8 in group B. Six patients in group A underwent doubling of serum creatinine concentration during vancomycin therapy, whereas none in group B did so. Serum creatinine doubled to >0.6 mg/dL in only 3 infants (all in group A). Any increase in serum creatinine to >0.6 mg/dL was seen in 10 infants, 9 of whom were in group A. No confounding variable, including previous or concomitant underlying disease states associated with renal dysfunction or treatment with other potentially nephrotoxic agents, were associated with a significant rise in serum creatinine.
Vancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations >40 microg/mL.
本研究旨在比较稳态时万古霉素血清峰值浓度≤40μg/mL的新生儿与万古霉素血清峰值浓度>40μg/mL的新生儿中肾毒性（定义为基线血清肌酐浓度翻倍）的发生率。次要目的是将合并疾病状态和潜在的肾毒性药物治疗与万古霉素接受者的血清肌酐升高情况相关联。
从现有数据库和病历回顾中确定1985年至1995年间接受万古霉素治疗超过3天、经培养证实为金黄色葡萄球菌或凝固酶阴性葡萄球菌败血症的新生儿。本研究纳入的所有69例患者均进行了系列血清肌酐测定，包括开始万古霉素治疗后48小时内的基线值，以及至少3剂后测定的血清万古霉素浓度，分别在60分钟输注后1小时和给药前15至30分钟测定峰值和谷值浓度。排除患有先天性肾或心脏异常的婴儿。记录人口统计学特征、万古霉素给药方案、血清万古霉素浓度和采样时间、合并药物治疗及疾病状态。患者分为A组（万古霉素峰值浓度≤40μg/mL）和B组（万古霉素峰值浓度>40μg/mL）。测定万古霉素治疗开始和结束时血清肌酐浓度的变化。如果万古霉素治疗开始至结束期间血清肌酐在任何时间翻倍，则判定为肾毒性。在额外分析中使用肾毒性的替代定义（血清肌酐任何升高至>0.6mg/dL或新的尿沉渣异常）。
共确定69例可评估患者（胎龄28.9±3.0周；出生体重1219±516g），A组61例，B组8例。A组6例患者在万古霉素治疗期间血清肌酐浓度翻倍，而B组无此情况。仅3例婴儿（均在A组）血清肌酐翻倍至>0.6mg/dL。10例婴儿血清肌酐升高至>0.6mg/dL，其中9例在A组。没有混杂变量，包括与肾功能不全相关的既往或合并基础疾病状态或用其他潜在肾毒性药物治疗与血清肌酐显著升高相关。
即使血清峰值浓度>40μg/mL，万古霉素相关肾毒性在新生儿中也很罕见。
