Adjustment of Aminoglycoside Dosing Based on Peak Serum Concentration and Bacterial Minimal Inhibitory Concentration
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 151
- 试验地点
- 1
- 主要终点
- Efficacy outcome
研究概览
简要总结
Aminoglycoside (AG) antibiotics have been in clinical use since the 1960s for treating various infections. The main safety concern related to AG use is nephrotoxicity. Based on validated pharmacokinetic-pharmacodynamic (PK-PD) principles shown to predict efficacy, AG dosing has shifted over the past 2 decades from multiple daily dosing to extended-interval dosing, with concomitant reduction in nephrotoxicity. Currently, AG daily dose is calculated according to the patients' adjusted body weight, assuming a common minimal inhibitory concentration (MIC) value.
We hypothesize that once pathogen identity and actual MIC become available, AG daily doses may be further adjusted, using the same PK-PD indices.
In order to investigate this hypothesis, we are conducting a prospective clinical study in which AG doses will be adjusted based on patient- and pathogen-specific factors, while assessing efficacy and safety.
详细描述
Intervention for all eligible patients:
calculation of Cmax/MIC based on MIC determination and timely peak level determination performed 30 minutes after the first or second AG dose following pathogen identity and MIC availability (as Individual timely monitoring is essential for individual dose adjustment, this will require one additional blood sample to routine clinical practice). If a peak-level monitoring is not available, Cmax will be assessed using commonly used pharmacokinetic prediction tools (equations/calculators.
- If Cmax/MIC=8-12 - no intervention (aminoglycoside dose unchanged).
- If Cmax/MIC>12 - decreasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC~10;
- If Cmax/MIC<8 - increasing AG dose accordingly, based on clinical calculators, to achieve target Cmax/MIC~10; If the calculated dose is larger than acceptable AG dosing, an infectious diseases physician will be consulted for need for alternative therapy.
- If AG dose has been adjusted, ascertaining PK/PD target attainment (repeat timely peak level determination following dose adjustment).
- Monitoring clinical and microbiological course and outcomes:
5.1 Clinical efficacy microbiological and clinical cure, in-hospital mortality 5.2 Safety - renal function during therapy, at end of therapy and at discharge or at day 7 after end of therapy, whichever is earlier. Any deterioration in renal function compared with baseline will be categorized according to the RIFLE criteria.
5.3 Aminoglycoside dosing data (proportion end extent of dose adjustments performed)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Neurosurgical infections, pneumonia, endocarditis or endovascular infections
- •eGFR<40ml/min
- •Empirical aminoglycoside treatment
- •Non Gram-negative pathogen
- •No MIC available for the pathogen
- •Expected remaining treatment duration of less than 4 days
研究组 & 干预措施
Aminoglycoside dose adjustment
Eligible patients will be assessed for attainment of PK/PD target under standard dosing, dose adjustment to attain target will be proposed where appropriate
干预措施: Aminoglycoside dose adjustment (Drug)
结局指标
主要结局
Efficacy outcome
时间窗: up to 1 week after end of therapy
proportion of patients where treatment failure was suspected and attributed to AG dose reduction
Renal outcome
时间窗: up to 1 week after end of therapy
Mean serum creatinine change at end of therapy vs. baseline
Aminoglycoside dosing outcomes:
时间窗: up to 1 week after end of therapy
Mean change in AG dose following adjustment
次要结局
未报告次要终点