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临床试验/NCT07087301
NCT07087301已完成不适用

A Prospective Observational Study to Analyze Factors Influencing Vancomycin Blood Concentrations in Post-Cardiac Surgery Patients Under Extracorporeal Circulation

Pengqiang Du1 个研究点 分布在 1 个国家目标入组 350 人开始时间: 2023年1月1日最近更新:
干预措施
相关药物

试验速览

阶段
不适用
状态
已完成
发起方
入组人数
350
试验地点
1
主要终点
Vancomycin trough concentration

研究概览

简要总结

The benefits of antimicrobial prophylaxis for cardiac surgery have been clearly demonstrated in placebo-controlled studies. Prophylactic intravenous antibiotics are therefore administered, with agent selection directed against the most common skin-colonising and gram-negative bacteria. Controversy persists regarding the optimal antimicrobial choice and duration of administration for cardiac surgery. In settings with a high incidence of methicillin-resistant Staphylococcus aureus (MRSA), administration of cefazolin or vancomycin for prophylaxis is considered reasonable (Class IIB recommendation, Level of Evidence C).

Vancomycin, a glycopeptide antibiotic, is widely used to treat serious gram-positive infections, including those caused by MRSA and methicillin-resistant Staphylococcus epidermidis (MRSE). Extensive pharmacokinetic/pharmacodynamic (PK/PD) studies reveal marked variability in population PK parameters across patient groups; clearance variability may reach 45 % and volume of distribution variability 48 %.

Oral vancomycin absorption is poor (≈5 % bioavailability), yet luminal concentrations remain sufficiently high for efficacy against Clostridioides difficile-associated pseudomembranous colitis. Inter-individual PK variability is substantial; two- or three-compartment models are typically employed. Protein binding ranges from 30 % to 50 %. Approximately 90 % of the dose is eliminated unchanged via the kidneys; biliary elimination is minimal. The elimination half-life is 4-7 h in individuals with normal renal function and is prolonged in patients >65 years or with renal impairment. Obesity, age, renal function, concomitant medications, disease state, and peri-operative interventions can all influence vancomycin clearance and apparent volume of distribution, potentially yielding sub- or supra-therapeutic serum concentrations.

To characterise current therapeutic drug monitoring (TDM) practices for vancomycin in cardiac-surgery patients undergoing cardiopulmonary bypass, this retrospective study combined multimodal data to develop a prognostic model predicting high- or low-risk vancomycin serum levels post-operatively. Model performance was evaluated to provide an evidence base for individualised dosing strategies aimed at optimising efficacy and minimising adverse effects.

Pharmacokinetic datasets from post-cardiac-surgery patients receiving cardiopulmonary bypass were analysed to identify determinants of vancomycin blood concentrations. Integration of baseline characteristics and medication records supports early intervention guidance for individualised vancomycin dosing and optimisation of anti-infective therapy.

研究设计

研究类型
Observational
观察模型
Case Control
时间视角
Retrospective

入排标准

年龄范围
18 Years 至 —(Adult, Older Adult)
性别
All
接受健康志愿者

入选标准

  • Undergoing cardiac surgery with cardiopulmonary bypass
  • Received intravenous vancomycin postoperatively for infection prophylaxis or treatment

排除标准

  • Age <18 years
  • Missing data on weight, height, or serum creatinine during vancomycin therapy
  • No vancomycin trough plasma concentration recorded

研究组 & 干预措施

nephrotoxicity risk group

nephrotoxicity risk group (≥20 mg/L vs <20 mg/L, n=350). A dual-model framework was established based on vancomycin's therapeutic window (10-20 mg/L): the first model (for nephrotoxicity risk prediction) defined high concentration as ≥20 mg/L and control as <20 mg/L to identify risk factors for vancomycin accumulation.

干预措施: subtherapeutic concentration risk group (Drug)

结局指标

主要结局

Vancomycin trough concentration

时间窗: Day 3 pre-dose

Pre-dose vancomycin serum concentration at steady state

次要结局

  • Cardiopulmonary Bypass Duration(Intra-operative (from initiation to termination of bypass))
  • Creatinine Clearance(Baseline)

研究者

发起方
Pengqiang Du
申办方类型
Other
责任方
Sponsor Investigator
主要研究者

Pengqiang Du

Associate Chief Pharmacist

Chinese Academy of Medical Sciences, Fuwai Hospital

研究点 (1)

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