Yoon Jin Gu, Huh Kyungmin, Sohn You Min, Park Hyo Jung, Na Soo Jin, Jeon Kyeongman
Department of Critical Care Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Division of Infectious Diseases, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
J Thorac Dis. 2021 Feb;13(2):768-777. doi: 10.21037/jtd-20-2243.
Vancomycin is the treatment of choice for serious methicillin-resistant (MRSA) infections. Current guidelines recommend giving an initial loading dose (LD) of 25-30 mg/kg to rapidly increase the serum concentration. However, high-quality evidence for the clinical benefit of LD is lacking. Herein, we aim to examine the association between vancomycin LD and clinical outcome.
A retrospective cohort study was conducted on adult patients treated for MRSA pneumonia with vancomycin in medical intensive care units from April 2016 to August 2018. MRSA pneumonia was defined by the Centers for Disease Control and National Healthcare Safety Network definition. The primary outcome was the clinical cure of pneumonia. Secondary outcome measures included time to pharmacokinetic (PK) target attainment, microbiological cure, acute kidney injury, and all-cause mortality.
A total of 81 patients were included; of these 22 (27.2%) received LD. The mean initial dose was significantly higher in the LD group. Clinical cure was similar in both groups (68.2% 66.1% in the LD and non-LD groups, respectively; P=0.860). No significant difference was observed in the microbiological cure, all-cause mortality, and incidence of acute kidney injury. Furthermore, no difference was observed in terms of time to PK target attainment (69.2 63.4 h in the LD and non-LD groups, respectively; P=0.624). Vancomycin minimum inhibitory concentration of <2 mg/L was identified as an independent predictive factor for clinical cure in multivariable analysis, whereas vancomycin LD was not.
Initial LD is not associated with better clinical outcome or rapid pharmacological target attainment in critically ill patients with MRSA pneumonia. Further studies are warranted to provide better evidence for this widely recommended practice.
万古霉素是治疗严重耐甲氧西林金黄色葡萄球菌（MRSA）感染的首选药物。当前指南推荐给予25 - 30mg/kg的初始负荷剂量（LD）以迅速提高血清浓度。然而，缺乏关于负荷剂量临床益处的高质量证据。在此，我们旨在研究万古霉素负荷剂量与临床结局之间的关联。
对2016年4月至2018年8月在医疗重症监护病房接受万古霉素治疗MRSA肺炎的成年患者进行回顾性队列研究。MRSA肺炎根据疾病控制中心和国家医疗安全网络的定义确定。主要结局是肺炎的临床治愈。次要结局指标包括达到药代动力学（PK）目标的时间、微生物学治愈、急性肾损伤和全因死亡率。
共纳入81例患者；其中22例（27.2%）接受了负荷剂量。负荷剂量组的平均初始剂量显著更高。两组的临床治愈率相似（负荷剂量组和非负荷剂量组分别为68.2%和66.1%；P = 0.860）。在微生物学治愈、全因死亡率和急性肾损伤发生率方面未观察到显著差异。此外，在达到PK目标的时间方面也未观察到差异（负荷剂量组和非负荷剂量组分别为69.2小时和63.4小时；P = 0.624）。在多变量分析中，万古霉素最低抑菌浓度<2mg/L被确定为临床治愈的独立预测因素，而万古霉素负荷剂量不是。
对于患有MRSA肺炎的重症患者，初始负荷剂量与更好的临床结局或快速达到药理学目标无关。有必要进行进一步研究，为这一广泛推荐的做法提供更好的证据。
