Hemmann Brianna, Woods Elizabeth, Makhlouf Tanya, Gillette Chris, Perry Courtney, Subramanian Mary, Hanes Holly
Department of Pharmacy (BH), Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Departments of Pharmacy (EW, TM, CP, MS), Wake Forest Baptist Health Brenner Children's Hospital, Winston-Salem, NC.
J Pediatr Pharmacol Ther. 2022;27(7):655-662. doi: 10.5863/1551-6776-27.7.655. Epub 2022 Sep 26.
Aminoglycosides are frequently used for empiric and definitive treatment of cystic fibrosis (CF) pulmonary exacerbations. Various methods have been described for aminoglycoside therapeutic drug monitoring. The objective of this study is to evaluate the effect of patient-specific pharmacokinetic calculations for aminoglycosides used to treat CF pulmonary exacerbations.
Ambidirectional cohort study of patients admitted to a children's hospital from June 1, 2018, through February 28, 2019, and June 1, 2019, through February 8, 2021. The primary outcome was the occurrence of dosing changes after analysis of initial serum concentrations in either group. Secondary outcomes included occurrence of nephrotoxicity, duration of antibiotics, and length of stay.
Twenty-four patients (75%) in the intervention group versus zero in the control group required dosing adjustments after initial analysis of serum concentrations were completed (p < 0.001). There was not a statistically significant between-group difference for duration of antibiotics in days (median, 14 vs 13.5; Z, 1.07; p = 0.29) or length of stay (median, 11 vs 11; Z, -0.31; p = 0.76). There was also not a statistically significant between-group difference in forced expiratory volume in one second (FEV) change from admission to discharge (11.4% vs 13.9%; , 0.61; Degrees of Freedom, 39; p = 0.55). Two patients (6.25%) in the intervention group experienced nephrotoxicity compared with zero patients in the control group (risk difference, 6.25%; 95% CI, -2.14 to 14.64; number needed to harm, 16).
Patient-specific pharmacokinetic monitoring led to significantly more dosing changes and was associated with similar patient outcomes as trough-only monitoring. Further studies are needed to identify methods to optimize aminoglycoside dosing and monitoring for these patients with the goal of reducing toxicities while maximizing efficacy.
氨基糖苷类药物常用于囊性纤维化（CF）肺部加重期的经验性和确定性治疗。已有多种氨基糖苷类治疗药物监测方法被描述。本研究的目的是评估针对用于治疗CF肺部加重期的氨基糖苷类药物进行患者特异性药代动力学计算的效果。
对2018年6月1日至2019年2月28日以及2019年6月1日至2021年2月8日入住一家儿童医院的患者进行双向队列研究。主要结局是两组在分析初始血清浓度后给药剂量变化的发生情况。次要结局包括肾毒性的发生、抗生素使用时长和住院时间。
干预组中有24名患者（75%）在完成血清浓度初始分析后需要调整给药剂量，而对照组为零（p < 0.001）。两组在抗生素使用天数（中位数，14天对13.5天；Z值，1.07；p = 0.29）或住院时间（中位数，11天对11天；Z值， -0.31；p = 0.76）方面没有统计学上的显著组间差异。从入院到出院的一秒用力呼气量（FEV）变化在两组之间也没有统计学上的显著差异（11.4%对13.9%；，0.61；自由度，39；p = 0.55）。干预组中有2名患者（6.25%）发生肾毒性，而对照组为零患者（风险差异，6.25%；95%置信区间， -2.14至14.64；伤害所需人数，16）。
患者特异性药代动力学监测导致显著更多的给药剂量调整，并且与仅进行谷浓度监测时的患者结局相似。需要进一步研究以确定优化这些患者氨基糖苷类药物给药和监测的方法，目标是在最大化疗效的同时降低毒性。
