Open-label Randomized Clinical Trial Comparing Best Available Therapy With or Without Meropenem for Bloodstream Infections by Enterobacterales With Minimal Inhibitory Concentrations for Meropenem Above 32mg/L
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 13
- 试验地点
- 2
- 主要终点
- Days alive and free of hospitalization
研究概览
简要总结
Enterobacterales resistant to carbapenem are cause of severe concern in hospital-acquired infections since therapeutic options are limited. Recently approved drugs, such as bela-lactam/beta-lactamase inhibitor, have been the drug of choice. However, its use is limited in low- and middle-income countries. Thus, therapy of these infections mostly relies on polymyxins and other old drugs.
The role of adjuvant carbapenem therapy in combination with polymyxins, aminoglycosides and other drugs is under investigation. From a pharmacokinetic/pharmacodynamic (PK/PD), there is an elevated probability that high-dose, extended infusion administered meropenem reach the PK/PD target of 40% above the minimal inhibitory concentration (MIC) of the pathogen when the MIC is 32mg/L or lower (non-susceptible isolates have MICs of 4mg/L or higher). However, the MIC is not routinely determined in clinical laboratories. In addition, high-level (above 32mg/L) resistance to carbapenems have been reported in many studies.
This open-label, randomized clinical trial aim to assess if the addition of meropenem to the best available therapy can increase the number of days alive and free of hospitalization in patients with bloodstream infections by Enterobacterales with MIC of meropenem above 32mg/L.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary or secondary bloodstream infections by any specie of the Enterobacterales family with minimum inhibitory concentration (MIC) for meropenem >32mg/L;
- •Agreement of the assistant team with the inclusion of the patient in the study;
- •Agreement by the patient or legal guardian to sign the informed consent form.
排除标准
- •Known pregnancy;
- •Patients belonging to the population deprived of their liberty;
- •Known allergy to meropenem;
- •Use of ceftazidime-avibactam (or any other new antimicrobial agent that become available in Brazil during the study period) for the treatment of the current infection;
- •Infection by an Enterobacterales isolates without in vitro susceptibility to at least one antimicrobial drug;
- •Bloodstream co-infection by another gram negative bacilli;
- •Concomitant infection at any site by a pathogen which meropenem is indicated;
- •Neutropenia (<1000 neutrophils cells/mm3)
- •Death expected within 48 hours of eligibility assessment.
研究组 & 干预措施
Meropenem plus Best Available Therapy plus
Meropenem 2g every 8 hours combined with the best available therapy (BAT). BAT will be defined according to the susceptibility profile and decision of the assistant team before randomization and should include at least one of the antimicrobials that, usually, have in vitro activity against carbapenem-resistant Enterobacterales isolates.
- Polymyxin B or colistimethate;
- Amikacin or gentamicin;
- Tigecycline;
- Another antimicrobial with in vitro susceptibility.
Doses will be defined by the assistant team.
干预措施: Meropenem (Drug)
结局指标
主要结局
Days alive and free of hospitalization
时间窗: 60 days
Number of days in which patients are alive and out of the hospital
次要结局
- Overall mortality(14, 28 and 60 days after randomization)
- Relapse of infection(60 days after randomization)
- Clostridioides difficile infection(60 days after randomization)
- Meropenem-related adverse effects(14 days after randomization)
- Acute Kidney Injury(14 days after randomization)
- Antimicrobial-free days(60 days after randomization)
研究者
Alexandre Prehn Zavascki
Principal Investigator
Hospital de Clinicas de Porto Alegre