Procalcitonin to Guide Antibiotic Stop in Neurocritical Care Patients. An Interventional Matched-cohort Study.
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 132
- 试验地点
- 2
- 主要终点
- Antibiotic use
研究概览
简要总结
Antibiotic overconsumption has been considered as one of the major contributive factors of the emergence of multidrug resistant bacteria, a serious threat particularly in intensive care units. Antibiotic stewardship programs are set up to meet this problem. Shortening the duration of antimicrobial therapy seems to be one of the strongest tools of these programs. Nevertheless, the decision to stop antibiotics in a critical care patients remains often challenging in real-life practice.
Procalcitonin (PCT), an inflammatory biomarker, has a promising profile and scores better than traditionally biomarkers as c-reactive protein (crp) and leucocytosis. Although two big multicenter randomised controlled trials showed a positive impact of PCT use in Intensive Care Unit (ICU), as it led to reduction of antibiotic exposure, the efficiency of this biomarker is still a point of debate. Notably the cost of PCT determination is a counterargument for its routinely use as it is a quite expensive test and its cost-benefit ratio has not been well studied.
The objective of this study is to test a PCT-algorithm for stopping antibiotics in a real life setting by assessing its impact on antibiotic consumption. The investigators hypothesize that it will shorten antimicrobial courses and will decrease overconsumption, with a possible positive impact on the increase of antimicrobial resistance and with no apparent adverse outcome.
详细描述
This is a single center, before-after, matched cohort study in a ICU of a non-university hospital. It puts the focus on neurocritical care patients as they are prone to infectious complications and these cases are often less straightforward in terms of diagnosis and management. The investigators hypothesise that such an algorithm, in addition to clinical judgement of the ICU physician, will reduce the duration of antibiotic treatment and the overall antibiotic use, could reduce selective pressure, without increase of mortality or recurrent infections.
All patients admitted to ICU with a primary non-infectious neurologic pathology will be screened for eligibility. Eligible patients can be enrolled if they meet all the inclusion criteria, there are no exclusion criteria, a matched control is available and an informed consent has provided by the patient or his or her legal representative. Patients included in the intervention group will be 1:1 matched with a patient out of the historical control group. Therefore, three fixed and two variable criteria for matching will be used. The fixed ones are: 1. pathology (traumatic brain injury; intracerebral/subarachnoid hemorrhage due to cerebral aneurysm or arteriovenous malformation; ischemic stroke; hemorrhagic stroke or other intracranial hemorrhage from; and the whether or not need for intervention (none, endovascular or neurosurgical intervention) . 2. need for mechanical ventilation within the first 12 hours after admission and 3. Glasgow coma scale (GCS) < 8 versus ≥ 8 at ICU admission or before starting sedation or anesthesia.
The two variable criteria are age (with a range of plus or minus 10 years) and the Acute Physiology and Chronic Health Evaluation (APACHE)-II score (with a range of plus or minus 15 points).
Matching will be manually, blinded for the outcome. A control group has been composed by analysing retrospectively patients admitted to our ICU from January 2016 on.
In the intervention group, doctors are additionally provided with PCT levels on regular base and with a non-binding advice on continuation or discontinuation of antibiotic therapy by electronic patient data management system feedback and by the involved microbiologist. The first PCT value will be used just as base-line, without any therapeutic consequence. Measurements will be repeated every 3-4 days, the last one is scheduled at day 27.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 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
- •patients admitted to the ICU with a primary non-infectious neurological pathology:
- •Traumatic Brain Injury
- •Intracerebral Bleeding (pe. subarachnoid bleeding) due to aneurysm or arteriovenous malformation
- •Ischemic Stroke Stroke
- •Hemorrhagic stroke or other intracranial haemorrhage
- •Other non-infectious neurologic condition (as hydrocephalus, status epilepticus, postoperative complication after elective neurosurgery, ...)
- •requiring antibiotics within the first week (day 0 - day 6) after ICU-admission for a suspected bacterial infection
排除标准
- •severe immunodeficiency and/or neutropenia: defined as (1) solid-organ transplant recipients with immunosuppressive therapy (monotherapy with corticosteroids is allowed), (2) recent chemotherapy in last 6 months, (3) hematologic malignancy with active therapy in last 2 years, (4) bone marrow transplant, (5) HIV patient with clinical complications (Pneumocystis jirovecii, Kaposi's sarcoma, lymphoma, tuberculosis, toxoplasmosis, ...) or CD4 count < 200/mm3, while neutropenia has been defined as white cell count < 1000/ml.
- •microbiologically proven infection with Pseudomonas, Acinetobacter baumannii, Lysteria or atypical pathogen as Chlamydia, Legionella or Mycoplasma; or Staphylococcal aureus bacteremia
- •microbiologically proven meningitis or ventriculitis
- •compartmentalised infection: pe. abscess, empyema
- •microbiologically proven (co-)infection making a prolonged antibiotic course necessary, such as endocarditis, prosthetic joint infection or septic arthritis, osteomyelitis, chronic prostatitis, ...
- •already > 24h on antibiotics before ICU admission
- •(expected) ICU length of stay < 7 days
- •no match available in the historical 'Standard of Care' group
- •no Informed Consent obtained
研究组 & 干预措施
Standard of Care group
Historical Group = Standard of Care group. Decision for stopping antibiotics taken by ICU physician: assessment on the basis of the clinical picture and traditional inflammatory biomarkers such as crp and leucocytosis
Procalcitonin group
ICU physician gets on regular base PCT value, what can be used as additive tool in the decision-making for stopping antibiotics.
干预措施: Procalcitonin group (Diagnostic Test)
结局指标
主要结局
Antibiotic use
时间窗: at day 28
We will measure the duration of the first uninterrupted antibiotic course, expressed as Days of Therapy (DOT) and as Defined Defined Daily Doses (DDD) and the Antibiotic consumption during first 28 days expressed as antibiotic free days (alive) within the first 28 days after inclusion.
次要结局
- 28-days mortality (from all causes)(at day 28)
- Hospital mortality(up to 6 months after inclusion)
- Recurrent infection(at day 28)
- ICU and mortality(up to 6 months after inclusion)
- Multidrug Resistance(up to 6 months after inclusion)
- ICU and hospital length of stay(up to 6 months after inclusion)
- Duration of Mechanical ventilation(at day 28)
- Reinfection(at day 28)
研究者
Stoffel Lamote
Stoffel Lamote, MD
General Hospital Groeninge