McQueen Katherine E, Clark Dana W
Department of Pharmacy, Children's Healthcare of Atlanta, Atlanta, Georgia.
J Pediatr Pharmacol Ther. 2016 Jul-Aug;21(4):332-338. doi: 10.5863/1551-6776-21.4.332.
To determine if the incidence of nephrotoxicity is higher in pediatric patients treated with the combination of vancomycin and piperacillin-tazobactam, compared to patients treated with vancomycin alone. Secondary objectives were to determine if admission to an intensive care unit (ICU), higher serum vancomycin trough concentrations (>15 mg/L), or receipt of other nephrotoxic agents were related to the development of nephrotoxicity. This was a retrospective, single-center, cohort study of 79 patients treated with vancomycin and 106 patients treated with vancomycin and pipracillin/tazobacatam (TZP). Serum creatinine was trended to determine if patients had nephrotoxicity, which was defined as at least a 100% increase in serum creatinine or an increase of ≥0.5 mg/dL from the baseline value. Fisher's exact test was used to compare the incidence of nephrotoxicity in the vancomycin group to the combination group. Secondary objectives were evaluated by using relative risk (RR). Nephrotoxicity developed in 3 of 79 patients (3.8%) in the vancomycin group and in 25 of 106 patients (23.6%) on combination therapy (p = 0.0001). In patients receiving only vancomycin, there was no statistically significant increase in nephrotoxicity for patients in the ICU (RR 1.85, 95% confidence interval [CI] 0.175-19.62, p = 0.61), those with higher vancomycin troughs (RR 2.32, CI 0.226-23.86, p = 0.48), or those receiving other nephrotoxic medications (RR 2.94, CI 0.2779-31.05, p = 0.37). In the combination group, having higher serum vancomycin trough concentrations increased the risk of nephrotoxicity (RR 5.22, CI 2.407-11.306, p < 0.0001). Combination therapy with vancomycin and TZP is potentially more nephrotoxic than vancomycin alone. ICU admissions, high vancomycin troughs (>15 mg/L), and concomitant nephrotoxic medications cannot be excluded as risk factors for the observed increase in nephrotoxicity in patients receiving vancomycin and TZP.
为了确定与仅接受万古霉素治疗的患者相比，接受万古霉素与哌拉西林 - 他唑巴坦联合治疗的儿科患者中肾毒性的发生率是否更高。次要目标是确定入住重症监护病房（ICU）、较高的血清万古霉素谷浓度（>15 mg/L）或接受其他肾毒性药物是否与肾毒性的发生有关。这是一项回顾性、单中心队列研究，纳入了79例接受万古霉素治疗的患者和106例接受万古霉素与哌拉西林/他唑巴坦（TZP）联合治疗的患者。通过观察血清肌酐变化趋势来确定患者是否发生肾毒性，肾毒性定义为血清肌酐至少升高100%或较基线值升高≥0.5 mg/dL。采用Fisher精确检验比较万古霉素组和联合治疗组的肾毒性发生率。次要目标通过相对风险（RR）进行评估。万古霉素组79例患者中有3例（3.8%）发生肾毒性，联合治疗组106例患者中有25例（23.6%）发生肾毒性（p = 0.0001）。在仅接受万古霉素治疗的患者中，入住ICU的患者（RR 1.85，95%置信区间[CI] 0.175 - 19.62，p = 0.61）、万古霉素谷浓度较高的患者（RR 2.32，CI 0.226 - 23.86，p = 0.48）或接受其他肾毒性药物的患者（RR 2.94，CI 0.2779 - 31.05，p = 0.37），肾毒性均无统计学显著增加。在联合治疗组中，较高的血清万古霉素谷浓度会增加肾毒性风险（RR 5.22，CI 2.407 - 11.306，p < 0.0001）。万古霉素与TZP联合治疗可能比单独使用万古霉素更具肾毒性。不能排除入住ICU、高万古霉素谷浓度（>15 mg/L）以及同时使用肾毒性药物是接受万古霉素和TZP治疗患者中观察到的肾毒性增加的风险因素。
