Abstract：
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infections are a serious threat to public health. Vancomycin (VAN) remains the primary treatment for these infections, and achieving the recommended area under the curve (AUC) target has been linked to improved clinical outcomes. The current VAN therapeutic monitoring guidelines recommend a loading dose (LD) of 20-35 mg/kg to rapidly attain targeted VAN exposures within 24 h of therapy. However, there is a paucity of data describing the impact of VAN LD on day 1 area under the curve (AUC0-24). This study aims to employ pharmacokinetic (PK) equations to calculate and describe the AUC0-24 following a VAN LD of 20 mg/kg.
METHODS: This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC0-24. Therapeutic AUC0-24 was defined as 400-600 mg/l*h.
RESULTS: Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m2 and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC0-24, while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC0-24, patients with subtherapeutic AUC0-24 were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m2 (67 vs. 52%). In contrast, patients with supratherapeutic AUC0-24 were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC0-24. CONCLUSIONS: Only 50% of patients achieve the target AUC0-24 following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations.
METHODS: This was a retrospective study of adult patients who were loaded with VAN 20 mg/kg, received ≥ 48 h of treatment, and had two consecutive serum VAN levels collected within 24 h. Linear, non-trapezoidal PK equations and two post-infusion VAN levels were used to calculate AUC0-24. Therapeutic AUC0-24 was defined as 400-600 mg/l*h.
RESULTS: Among 123 included patients, the median age was 46 years (IQR 36, 62), 54% (67/123) of the patients had a body mass index (BMI) ≥ 30 kg/m2 and 27% (33/123) were admitted to the intensive care unit (ICU). Following a LD of 20 mg/kg, 50% (61/123) of the patients met the therapeutic AUC0-24, while 22% (27/123) of the patients were subtherapeutic, and 28% (35/123) were supratherapeutic. Compared with patients who achieved therapeutic AUC0-24, patients with subtherapeutic AUC0-24 were more likely to be younger (44 vs. 37 years old) and have a BMI ≥ 30 kg/m2 (67 vs. 52%). In contrast, patients with supratherapeutic AUC0-24 were more likely to be older (64 vs. 44 years old) and to have chronic kidney disease diagnosis (23 vs. 7%) when compared to patients who achieved a therapeutic AUC0-24. CONCLUSIONS: Only 50% of patients achieve the target AUC0-24 following a VAN 20 mg/kg LD, with younger, heavier patients underexposed and older patients with renal impairment overexposed, suggesting that different dosing strategies are needed for these populations.
摘要：
背景：耐甲氧西林金黄色葡萄球菌（MRSA）感染是对公众健康的严重威胁。万古霉素（VAN）仍然是这些感染的主要治疗方法，达到推荐的曲线下面积(AUC)目标与改善的临床结局相关.当前的VAN治疗监测指南建议20-35mg/kg的负荷剂量（LD），以在治疗后24小时内迅速达到目标VAN暴露。然而,缺乏描述VANLD对第1天曲线下面积(AUC0-24)影响的数据.本研究旨在使用药代动力学（PK）方程来计算和描述VANLD为20mg/kg后的AUC0-24。
方法：这是一项对服用VAN20mg/kg的成年患者的回顾性研究，接受≥48小时的治疗，并在24小时内收集了两个连续的血清VAN水平。线性，非梯形PK方程和两个输注后VAN水平用于计算AUC0-24.治疗性AUC0-24定义为400-600mg/l*h。
结果：在123名纳入的患者中，中位年龄为46岁(IQR36,62)，54％（67/123）的患者体重指数（BMI）≥30kg/m2，27％（33/123）的患者入院重症监护病房（ICU）。在LD为20mg/kg之后，50%(61/123)的患者满足治疗AUC0-24,而22%(27/123)的患者为亚治疗,28%(35/123)为超治疗性。与达到治疗性AUC0-24的患者相比，亚治疗性AUC0-24的患者更可能年轻（44vs.37岁），BMI≥30kg/m2（67vs.52%)。相比之下,具有超治疗性AUC0-24的患者更可能年龄较大（64与44岁）并有慢性肾脏疾病诊断（23岁与7％）与达到治疗AUC0-24的患者相比。结论：只有50％的患者在VAN20mg/kgLD后达到目标AUC0-24，更年轻,重度患者曝光不足和老年患者肾功能损害过度曝光，这表明这些人群需要不同的给药策略。
方法：这是一项对服用VAN20mg/kg的成年患者的回顾性研究，接受≥48小时的治疗，并在24小时内收集了两个连续的血清VAN水平。线性，非梯形PK方程和两个输注后VAN水平用于计算AUC0-24.治疗性AUC0-24定义为400-600mg/l*h。
结果：在123名纳入的患者中，中位年龄为46岁(IQR36,62)，54％（67/123）的患者体重指数（BMI）≥30kg/m2，27％（33/123）的患者入院重症监护病房（ICU）。在LD为20mg/kg之后，50%(61/123)的患者满足治疗AUC0-24,而22%(27/123)的患者为亚治疗,28%(35/123)为超治疗性。与达到治疗性AUC0-24的患者相比，亚治疗性AUC0-24的患者更可能年轻（44vs.37岁），BMI≥30kg/m2（67vs.52%)。相比之下,具有超治疗性AUC0-24的患者更可能年龄较大（64与44岁）并有慢性肾脏疾病诊断（23岁与7％）与达到治疗AUC0-24的患者相比。结论：只有50％的患者在VAN20mg/kgLD后达到目标AUC0-24，更年轻,重度患者曝光不足和老年患者肾功能损害过度曝光，这表明这些人群需要不同的给药策略。
