Defining Adult Beta-lactam Antimicrobial Pharmacokinetics Across the Secondary Care Setting
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Fraction of the Dosing Interval Over Which the Concentration of Unbound Drug is Greater Than the Minimum Inhibitory Concentration (fT>MIC)
研究概览
简要总结
Currently in the UK, TDM is routinely performed for aminoglycosides and glycopeptide antimicrobial agents, given fears over the narrow therapeutic window of these agents and the serious adverse events associated with toxicity. However, in critical care the role of TDM for optimisation of therapy has been demonstrated to help optimise dosing of patients who tend to have variable pharmacokinetic parameters (J. A. Roberts et al,). This is of growing importance given that low concentrations of antimicrobial agents, below a micro-organisms minimum inhibitory concentration (MIC) is believed to be a major driver of AMR. The investigators set out to explore whether similar observations in PK-PD target variability are currently being observed across the secondary care setting (outside of critical care) and whether these appear to be impacting on clinical outcomes.
详细描述
STUDY PARTICIPANTS
- Participants receiving oral or intravenous therapy will be included in this study.
- Drug level sampling will be undertaken once the participant is at steady state (after at least 5 doses have been administered to those on treatment).
- All patients will be consented using the participation information leaflet and consent form provided in appendix 1.
DRUG LEVEL SAMPLING
- Patients will be identified for inclusion, and researchers will discuss inclusion in the study with the patient and provide clinical information for them to consider. Individuals will be recruited from all areas of secondary care (including, general medicine, general surgery, augmented care, and out-patient parenteral antimicrobial therapy [OPAT]).
- They will then be consented by researchers after being given at least 24 hours to consider this information and as long as the patient has expressed interest in participating to their treating physician.
- This will include permission for basic, anonymised demographic and clinical data to be collected related to the patients infection, for which they are receiving antimicrobial therapy.
- An extra 3mLs of blood will be collected during the patient's routine daily phlebotomy round following their consent. They will be enrolled for up to 72 hours or two days of routine blood tests (whichever is shorter). Up to 10 samples may be taken during the 2 days the patient is enrolled, depending on the number of routine blood tests the patient receives during that day. No more than 3mLs will be taken per each routine blood sample. For example, if the individuals will only have routine blood tests taken at 8am on day 1 and day 2. Then only two extra samples will be taken (3mLs on D1 and 3mLs on D2).
- The time they received their dose of antimicrobials, the length of infusion time (if available), and time the sample was collected will all be recorded.
- PK/PD indices for evaluation will be calculated post-hoc during pharmacokinetic-pharmacodynamic analysis. TDM sampling can occur at any time during the dosing schedule (in line with routine blood testing).
- A standard operating procedure for this study can be found in appendix 3.
SAMPLE PREPARATION AND ANALYSIS
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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
- •Adult subjects over 18 years old
- •Capacity to consent to participation
- •Receiving target antimicrobial (amoxicillin, amoxcillin-clavulanate, cefuroxime, ceftriaxone, flucloxacillin, meropenem, piperacillin-tazobactam) for at least 5 doses prior to sampling
- •Appropriate venous access (or for venous access to be gained)
排除标准
- •Children under 18 years old
- •Lacking capacity or prisoner
- •Anaemia or bleeding disorder, deemed significant by the patients physician
- •Patient's physician deems that they are not suitable for inclusion in the study
- •Patients unlikely to be receiving agent for study period
研究组 & 干预措施
Beta-lactam antibiotic
Observational pharmacokinetic study of non-critical care patients receiving beta-lactam antibiotics for management of infections.
干预措施: Beta-lactam antibiotic (Drug)
结局指标
主要结局
Fraction of the Dosing Interval Over Which the Concentration of Unbound Drug is Greater Than the Minimum Inhibitory Concentration (fT>MIC)
时间窗: Two to 10 samples taken during the first 120 hours of antimicrobial therapy
Minimum inhibitory concentration (MIC) is the concentration required to visibly inhibit microbial growth in vitro. The MIC for each drug was defined by non-species related breakpoints provided in EUCAST v11.0. Results are given as a fraction of the dosing interval over which the concentration of the unbound drug is greater than the MIC.
次要结局
未报告次要终点