Linezolid or Vancomycin Surgical Site Infection Prophylaxis
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 1,160
- 试验地点
- 1
- 主要终点
- Comparaison of the rates of SSIs in patients receiving vancomycin 30 mg/kg versus patients receiving linezolid 1200 mg as surgical antibiotic prophylaxis for all types of surgery
研究概览
简要总结
Anesthesia and surgical guidelines recommend the administration of a surgical antibiotic prophylaxis for patients undergoing "clean" surgery. The prescribed antibiotic should target the bacteria most commonly found in surgical site infections (SSIs) and the duration of administration should not exceed 24 hours to minimize the ecological risk of bacterial resistance emergence. Guidelines provide a framework for the administration of surgical antibiotic prophylaxis but their effectiveness is regularly re-evaluated by measuring the rates of SSIs and the microorganisms responsible for infectious complications after surgery.
The majority of interventions required the use of first or second generation cephalosporins as surgical antibiotic prophylaxis. For patients with allergy to beta-lactams, clindamycin and vancomycin are proposed as alternatives. In the patients with methicillin-resistant S. aureus (MRSA) colonization or if those at risk of developing MRSA-associated SSI (hospital ecology, previous antibiotic treatment), only vancomycin is recommended. Vancomycin pharmacokinetics and pharmacodynamics is complex and its tissue absorption varies according to the level of tissue inflammation. This is a difficult molecule to handle, exclusively administered via intravenous route.
Linezolid is a synthetic antibiotic from the oxazolidinone class. By binding to the rRNA on the 30S and 50S ribosomal subunits, it inhibits the bacterial synthesis. It is therefore a bacteriostatic antibiotic approved for the treatment of both methicillin susceptible S. aureus (MSSA) and MRSA infections. It also covers a broad spectrum of Gram positive bacteria. Its pharmacokinetics allows rapid intravenous infusion, with rapid penetration into bone and soft tissue of the surgical site during hip surgery. A large Cochrane meta-analysis reported that linezolid was superior to vancomycin in skin infections, including MRSA infections, albeit with low quality evidence.
We therefore hypothesized that linezolid can be used instead of vancomycin for beta-lactam allergic patients and patients at risk of MRSA-associated SSI in general surgery.
详细描述
Anesthesia and surgical guidelines recommend the administration of a surgical antibiotic prophylaxis for patients undergoing "clean" surgery. The prescribed antibiotic should target the bacteria most commonly found in surgical site infections (SSIs) and the duration of administration should not exceed 24 hours to minimize the ecological risk of bacterial resistance emergence.
Surgical site infections are devastating complications occurring after surgery. They can lead to prolonged and burdensome duration of hospitalization, resulting in impaired outcomes and additional costs.
Many infections are associated with Gram positive bacteria, mainly Staphylococcus aureus and Staphylococcus spp with negative coagulase. Large European cohorts reported that less than 10% of SSIs were associated with Gram negative bacteria, justifying the use of 1st and 2nd generation cephalosporin, clindamycin and vancomycin as surgical antibiotic prophylaxis.
Guidelines provide a framework for the administration of surgical antibiotic prophylaxis but protocols are discussed at the local level with an agreement between surgeons, anesthesiologists, infectious diseases specialists, microbiologists and pharmacists. They are subject to economic analyses, including head-to-head comparisons of different options. Their effectiveness is regularly re-evaluated by measuring the rates of SSIs and the microorganisms responsible for infectious complications after surgery.
The majority of interventions required the use of first or second generation cephalosporins as surgical antibiotic prophylaxis. For patients with allergy to beta-lactams, clindamycin and vancomycin are proposed as alternatives. In the patients with methicillin-resistant S. aureus (MRSA) colonization or if those at risk of developing MRSA-associated SSI (hospital ecology, previous antibiotic treatment), only vancomycin is recommended. Actually, clindamycin was found to be less effective than beta-lactams or vancomycin in reducing the risk of SSI; the reported odds ratios (OR) for SSIs as compared to cefazolin range from an OR of 1.38 (95%CI 1.11 to 1.71) to OR 3.45 (95% CI 1.84 to 6.47).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The treatment scheme of the study does not allow for double-blinded manipulations. Postoperative evaluations and measurements will be performed in a blinded fashion by an investigator different from the physician who managed the patient in the operating room: SSI rates, adverse events, and length of stay. Statistical analyses will be performed in a blinded fashion.
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 undergoing any elective surgery for which vancomycin is recommended in the guidelines as an alternative to beta-lactams including: neurosurgery, cardiac surgery, orthopedic surgery, vascular surgery, penile and testicular surgery, gastric banding procedure in digestive surgery.
- •This inclusion criteria can lead to the inclusion of patients who undergo a re-intervention provided that the re-intervention is not due to a suspected or proven infection and that the patient was not included in LOVip at the time of his/her first intervention;
- •Age ≥ 18 years-old;
- •Known allergy to beta-lactams AND/OR suspected or proven MRSA colonization. Proven MRSA colonization is defined as a positive patient sample (any type of swab or biological fluid) for MRSA within 3 months prior to surgery. MRSA colonization is suspected when the patient undergoing surgery has received antibiotic treatment within 3 months prior to surgery or is undergoing re-intervention more than 5 days after the first surgery. MRSA is defined as a strain of Staphylococcus aureus resistant to oxacillin or cefoxitin, predicting non-susceptibility to all classes of beta-lactam antimicrobials (except anti-MRSA cephalosporins) (6). In contrast, MSSA is defined as an oxacillin sensitive strain of Staphylococcus aureus;
- •Informed consent of the patient;
- •Affiliated to a social security system or equivalent.
排除标准
- •Surgery for suspected or proven SSI (definition of SSI provided on chapter 3.6.1 Primary endpoint as defined by (5, 7)) according to international definitions;
- •Obesity defined by a body mass index (BMI) > 35 kg/m2 or a body weight > 100 kg;
- •Chronic kidney disease defined as glomerular filtration rate (GFR) < 60 ml/min per 1.73m2;
- •Known allergy to linezolid or vancomycin;
- •Hematologic malignancy;
- •Declared pregnancy or breastfeeding;
- •Patient under legal protection regime for adults;
- •Patient denying consent;
- •Patient already included in LOVip for a previous surgery.
研究组 & 干预措施
Control group: Vancomycin
Patients receive a dose of 30 mg/kg of vancomycin (2 hours infusion) starting 2.5 hours before the scheduled time of surgical incision as defined in the French guidelines.
干预措施: Vancomycin Injection (Drug)
Experimental group: linezolid
Patients receive a dose of 1200 mg of linezolid (30 minutes infusion) 30 minutes before the scheduled time of surgical incision.
干预措施: Linezolid Injection (Drug)
结局指标
主要结局
Comparaison of the rates of SSIs in patients receiving vancomycin 30 mg/kg versus patients receiving linezolid 1200 mg as surgical antibiotic prophylaxis for all types of surgery
时间窗: Day 30 after surgery
The SSIs are defined according to the standardized and validated Centers for Disease Control (CDC) criteria, including three levels of infection (superficial, deep, organ or space) (10). These definitions were endorsed by Santé Publique France and are used by the ISO-Raisin Network for the surveillance of nosocomial infections.
次要结局
- Number of days from hospital admission to surgery, from surgery to discharge, from inclusion to discharge(Day-365)
- Antibiotic-free days during the 30-days following surgery(Day-30)
- Mortality rates In-hospital, at day-30, at day-90 and at day-365;(day-30, at day-90 and at day-365)
- Rates of Gram positive and Gram negative infections of any sites requiring antibiotic treatments(Day-365)
- Comparaison of treatment compliance(Day-365)
- Assessment of SSIs rates in all patients after 365 days(365 after surgery)
- Rates of MSSA and MRSA infections(Day-365)
- Preference-based utility score(Day-365)
- Total costs of care during the 30-day study period and associated costs over the 365-day study period in all patients;(30-Day and 365-day)