PipEracillin/Tazobactam vs mERoPENem for Treatment of AmpC-producing Bloodstream Infections: an Extension of the Original PETERPEN Trial
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 入组人数
- 1,000
- 试验地点
- 4
- 主要终点
- Treatment failure
研究概览
简要总结
Data regarding optimal treatment for extended-spectrum beta-lactamase (ESBL) producing Enterobacterales bloodstream infection are lacking. Observational studies show conflicting results when comparing treatment with combination beta-lactam-beta-lactamase inhibitor and carbapenems. The investigators aim to evaluate the effect of definitive treatment with meropenem vs. piperacillin-tazobactam on the outcome of patients with bacteremia due to cephalosporin-non-susceptible Enterobacteriaceae. The investigators hypothesize that piperacillin-tazobactam is non-inferior to meropenem.
详细描述
PeterPen-SPICE-M will expland the PeterPen trial. In PeterPen we recruit patients with bacteremia caused by 3rd generation cephalosporin-resistant E. coli or Klebsiella pneumoniae. In SPICE-M we will recruit also patients with bacteremia caused by 3rd generation cephalosporin-resistant Serratia marcescens, Providencia stuartii & rettgeri, Indole positive Proteus spp. (Proteus vulgaris), Citrobacter freundii, Enterobacter cloacae, Klebsiella aerogenes and Morganella morganii. In both trials patients will be allocated within 72 hours of blood culture taking to piperacillin-tazobactam vs. meropenem to complete at least 7 days of covering antibiotic therapy.
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
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults (age ≥ 18 years)
- •New onset BSI due to Serratia marcescens, Providencia spp., Morganella morganii, Citrobacter freundii, and Enterobacter spp.in one or more blood cultures associated with evidence of infection.
- •The microorganism will have to be non-susceptible to third generation cephalosporins (ceftriaxone and ceftazidime) and susceptible to both PTZ and meropenem (see microbiological methods).
- •Both community and hospital-acquired bacteremias will be included.
- •We will permit the inclusion of bacteremias due to study pathogens with concomitant growth in blood of skin commensals considered as contaminants.
排除标准
- •More than 72 hr. elapsed since initial blood culture taken, regardless of the time covering antibiotics were started (up to 72 hrs.).
- •Polymicrobial bacteremia. Polymicrobial bacteremia will be defined as either growth of two or more different species of microorganisms in the same blood culture, or growth of different species in two or more separate blood cultures within the same episode.
- •Patients with prior bacteremia or infection that have not completed antimicrobial therapy for the previous infectious episode.
- •Patients with septic shock at the time of enrollment and randomization, defined as at least 2 measurements of systolic blood pressure < 90 mmHg and/or use of vasopressors (dopamine>15μg/kg/min, adrenalin>0.1μg/kg/min, noradrenalin>0.1μg/kg/min, vasopressin any dose) in the 12 hours prior to randomization. In the absence of the use of vasopressors, a systolic blood pressure <90 would need to represent a deviation for the patient's known normal blood pressure.
- •BSI due to specific infections known at the time of randomization:
- •Endocarditis / endovascular infections
- •Osteomyelitis (not resected)
- •Central nervous system infections
- •Allergy to any of the study drugs confirmed by history taken by the investigator
- •Previous enrollment in this trial
- •Concurrent participation in another interventional clinical trial
- •Imminent death (researcher's assessment of expected death within 48 hrs. of recruitment) or patient in palliative care
研究组 & 干预措施
piperacillin tazobactam
干预措施: Piperacillin / Tazobactam Injection (Drug)
meropenem
干预措施: Meropenem (Drug)
结局指标
主要结局
Treatment failure
时间窗: 7 days from randomization]
death OR fever \> 38°C in the last 48 hours OR lack of resolution of symptoms attributed to the focus of infection OR Sequential Failure Organ Assessment (SOFA) score increasing OR positive blood cultures by the time point assessed
All-cause mortality
时间窗: 30 days from randomization
Primary Outcome Measure
次要结局
- Number of participants with treatment failure(14 days and 30 days from randomization)
- Secondary bacterial infections(90 days from randomization)
- Number of participants with hospital re-admissions(90 days from randomization)
- Number of participants with development of antimicrobial resistance(90 days from randomization)
- All-cause mortality(14 and 90 days from randomization])
- Number of participants with recurrent positive blood cultures (relapse)(30 days and 90 days from randomization)
- Number of participants with microbiological failure(7 days and 14 days from randomization)
- Number of participants with Clostridium difficile associated diarrhea(90 days from randomization)
- Carriage of carbapenemase-producing Enterobacteriaceae (CPE) and non-CPE carbapenem-resistant Enterobacteriaceae in-hospital detected by weekly rectal surveillance of carriage while in-hospital(90 days from randomization)
- Total in-hospital days(30 days and 90 days from randomization)
- Total antibiotic days(30 days and 90 days from randomization)
- Adverse events(30 days)
研究者
MICHAL PAUL md
Prof. Mical Paul, MD
Rambam Health Care Campus