Flannery Alexander H, Wallace Katie L, Rhudy Christian N, Olmsted Allison S, Minrath Rachel C, Pope Stuart M, Cook Aaron M, Burgess David S, Morris Peter E
Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, 789 S. Limestone Street, TODD 251, Lexington, KY 40536, USA Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA.
Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, KY, USA Department of Pharmacy Services, University of Kentucky HealthCare, Lexington, KY, USA.
Ther Adv Infect Dis. 2021 Mar 30;8:20499361211005965. doi: 10.1177/20499361211005965. eCollection 2021 Jan-Dec.
While vancomycin loading doses may facilitate earlier pharmacokinetic-pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults.
Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of a loading dose (⩾20 mg/kg actual body weight) or not. The primary outcome was clinical failure, a composite outcome of death within 30 days of first MRSA culture, blood cultures positive ⩾7 days, white blood cell count up to 5 days from vancomycin initiation, temperature up to 5 days from vancomycin initiation, or substitution (or addition) of another MRSA agent.
There was no difference in the percentage of patients experiencing clinical failure between the loading dose and no loading dose groups (74.8% 72.8%; = 0.698). Secondary outcomes were also similar between groups, including mortality and acute kidney injury, as was subgroup analysis based on site of infection. Exploratory analyses, including assessment of loading dose based on quartiles and a multivariable logistic regression model showed no differences.
Use of vancomycin loading doses was not associated with improved clinical outcomes in critically ill patients with MRSA infection.
虽然万古霉素负荷剂量可能有助于更早达到药代动力学-药效学目标,但负荷剂量对临床结局的影响仍研究不足。重症患者因耐甲氧西林金黄色葡萄球菌(MRSA)感染而发病和死亡的风险最高,据推测最有可能从负荷剂量中获益。我们试图确定在一组重症成年患者中接受万古霉素负荷剂量与临床结局之间的关联。
449例从血液或呼吸道标本中分离出MRSA培养物的重症患者符合该研究条件。根据是否接受负荷剂量(≥20mg/kg实际体重)建立队列。主要结局是临床失败,这是一个复合结局,包括首次MRSA培养后30天内死亡、血培养阳性≥7天、万古霉素开始使用后5天内白细胞计数、万古霉素开始使用后5天内体温,或更换(或添加)另一种MRSA药物。
负荷剂量组和无负荷剂量组临床失败患者的百分比无差异(74.8%对72.8%;P = 0.698)。两组间的次要结局也相似,包括死亡率和急性肾损伤,基于感染部位的亚组分析也是如此。探索性分析,包括基于四分位数评估负荷剂量和多变量逻辑回归模型,均未显示出差异。
对于MRSA感染的重症患者,使用万古霉素负荷剂量与改善临床结局无关。