Department of Pharmacy, Aga Khan University Hospital, Stadium Road (Main Pharmacy), P.O Box 3500, Karachi, 74800, Pakistan.
Department of Pediatrics & Child Health, Aga Khan University Hospital, Karachi, Pakistan.
BMC Pharmacol Toxicol. 2022 Aug 20;23(1):64. doi: 10.1186/s40360-022-00606-1.
Anecdotal experience and studies have shown that most pediatric patients fail to reach target therapeutic vancomycin trough levels (VTLs) and required higher total daily doses (TDD). This retrospective study aims to evaluate the frequency of hospitalized children who achieved target VTLs with a vancomycin (VNCO) dosing regimen of 40-60 mg/kg/d q6h and to assess the VNCO-TDD required to attain the target and their effects on clinical outcomes in pediatric patients.
After ethical approval, patients of 3 month-12 years were evaluated in this chart review study who received ≥ 3 intravenous-VNCO doses and appropriately drawn blood samples of VTLs between October 2019 to June 2020. Data were retrieved for demographic and clinical characteristics, culture reports, VNCO-regimen, subsequent steady-state VTLs, concomitant nephrotoxic medications, and serum creatinine. Clinical pharmacists made interventions in VNCO therapy and higher VNCO-TDD were used. Safety of higher vs standard daily doses and their clinical impact on duration of therapy, hospital stay, and survival were evaluated.
A total of 89 (39.1%) patients achieved target VTLs (SD-group). The smallest proportion (18.2%) of 2-6 years patients achieved target VTLs and reported the lowest mean value of 10.1 ± 0.2 mg/L which was a significant difference (p < 0.05) from all subgroups. Subtherapeutic VTLs were observed in 139 (60.9%) cases (HD-group), who received higher VNCO-TDD of 72 ± 8.9 mg/kg/d q6h to achieve the targets. Duration of therapy in culture-proven septic patients was significantly (p = 0.025) longer in SD-group [18.4 ± 12.2 days] than HD-group [15.1 ± 8.9 days]. Nephrotoxicity and electrolyte imbalance were comparable in groups. Length of hospital stay was significantly (p = 0.011) longer [median 22 (range 8-55) days] in SD-group compared to HD-group [median 16 (range 8-37) days]. Number of patients survived in HD-group were significantly (p = 0.008) higher than SD-group [129 (92.8%) vs 75 (84.3%)].
Initial Vancomycin doses of 72 ± 8.9 mg/kg/day q6h are required to achieve therapeutic target in 3 months to 12 years patients. High doses are not associated with higher nephrotoxicity than reported with low doses. In addition, efficient pharmacist intervention for the use of higher VNCO-TDD may improve clinical outcomes in terms of duration of therapy, hospital stay, and survival.
临床经验和研究表明,大多数儿科患者未能达到目标万古霉素谷浓度(VTL),需要更高的总日剂量(TDD)。本回顾性研究旨在评估接受 40-60mg/kg/d q6h 万古霉素(VNCO)剂量方案的住院患儿达到目标 VTL 的频率,并评估达到目标所需的 VNCO-TDD 及其对儿科患者临床结局的影响。
在获得伦理批准后,本研究对 2019 年 10 月至 2020 年 6 月期间接受了至少 3 次静脉 VNCO 治疗并适当抽取了 VTL 血样的 3 个月至 12 岁患者进行了图表回顾性评估。收集了人口统计学和临床特征、培养报告、VNCO 方案、后续稳态 VTL、同时使用的肾毒性药物和血清肌酐的数据。临床药师对 VNCO 治疗进行了干预,并使用了更高的 VNCO-TDD。评估了更高 vs 标准日剂量的安全性及其对治疗持续时间、住院时间和生存率的临床影响。
共有 89 名(39.1%)患者达到了目标 VTL(SD 组)。2-6 岁患者达到目标 VTL 的比例最小(18.2%),报告的平均 VTL 值为 10.1±0.2mg/L,与所有亚组相比差异有统计学意义(p<0.05)。在 139 名(60.9%)存在治疗性 VTL 的患者(HD 组)中,使用了更高的 VNCO-TDD 72±8.9mg/kg/d q6h 以达到目标。在培养阳性的败血症患者中,SD 组的治疗持续时间明显(p=0.025)更长[18.4±12.2 天],HD 组为[15.1±8.9 天]。两组的肾毒性和电解质失衡相当。SD 组的住院时间明显(p=0.011)更长[中位数 22(范围 8-55)天],HD 组为[中位数 16(范围 8-37)天]。HD 组的存活患者数量明显(p=0.008)高于 SD 组[129(92.8%)vs 75(84.3%)]。
对于 3 个月至 12 岁的患者,初始万古霉素剂量为 72±8.9mg/kg/d q6h 即可达到治疗目标。与低剂量相比,高剂量并不与更高的肾毒性相关。此外,临床药师通过使用更高的 VNCO-TDD 进行有效的干预,可能会改善治疗持续时间、住院时间和生存率方面的临床结局。