Antimicrobial Therapy for Infections Due to Pseudomonas Aeruginosa With Difficult-to-treat Resistance: a Real-world, Prospective, Multicenter Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 600
- 试验地点
- 48
- 主要终点
- Clinical cure rate
研究概览
简要总结
The primary objective of the ADDICT study is to assess and compare the clinical efficacy of available options for antimicrobial therapy (new beta-lactam/beta-lactamase inhibitor combination, cefiderocol or older agents such as aminoglycosides and colistin) in unselected patients with infection due to difficult-to-treat P. aeruginosa.
详细描述
Infections due to Pseudomonas aeruginosa isolates with acquired resistances to all first-line antipseudomonal beta-lactams and fluoroquinolones (difficult-to-treat isolates - DTR), pose serious therapeutical challenges, especially in critically ill and/or immunocompromised patients. Certain new beta-lactam/beta-lactamase inhibitor combinations (BL/BLI (beta lactamine/ beta lactamase inhibitor) - i.e., ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, others) and cefiderocol have shown promising results for the treatment of infections due to DTR P. aeruginosa. However, multicenter data on their real-life utilization in this indication are still scarce.
The ADDICT study is a prospective, multicenter cohort study including unselected patients with DTR P. aeruginosa infection requiring definite intravenous antimicrobial therapy. The primary objective of the study is to investigate the clinical efficacy of available options (new BL/BLI, cefiderocol or older agents such as aminoglycosides and colistin) in this population. Secondary objectives are to compare the clinical and microbiological efficacy of available options in infections due to DTR P. aeruginosa with in vitro susceptibility to more than one last-resort drug, to compare the incidence of non-ecological adverse events observed with these drugs, to assess the incidence of resistance emergence under therapy and to elucidate the molecular mechanisms of resistance emergence, to assess the benefits and risks of combination therapy in this indication, to compare the acquisition rates of multidrug-resistant bacteria other than DTR P. aeruginosa, and Clostridioides difficile infection, to compare Day-28 and in-hospital all-cause mortality rates.
Patients will be recruited in 60 hospital centers contributing to four French networks of research in infectious diseases and critical care (CRICS-TRIGGERSEP, ReaRezo, OutcomeRéa, RENARCI - PROMISE metanetwork). Clinical variables will be collected through an electronic case-report form. DTR P. aeruginosa isolates will be sent to the National Reference Center of Antimicrobial Resistance in P. aeruginosa for centralized analyses (extended antimicrobial susceptibility testing, MLST, whole-genome sequencing of successive isolates if resistance emergence under therapy).
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
- •All patients aged 18 or over and requiring intravenous definite antimicrobial therapy for a DTR P. aeruginosa infection
排除标准
- •Cystic fibrosis
- •P. aeruginosa DTR colonization or P. aeruginosa DTR infection not requiring definitive intravenous antibiotic therapy
- •Protected person (under guardianship or curatorship)
- •Persons under court protection
- •Persons deprived of liberty
- •Opposition expressed for participation in the study
结局指标
主要结局
Clinical cure rate
时间窗: Test of cure visit
Clinical responses will be assessed by local investigators. Clinical cure will be defined as a composite endpoint of survival with no relapse occurring since the end of definite therapy and the complete resolution of all initial clinical signs of infection at the ToC visit (all-cause deaths at the ToC visit will be considered as clinical failures).
Clinical cure
时间窗: Day 7±2 after the completion of definite therapy
Clinical responses will be assessed by local investigators. Clinical cure will be defined as a composite endpoint of survival with no relapse occurring since the end of definite therapy and the complete resolution of all initial clinical signs of infection at the ToC visit (all-cause deaths at the ToC visit will be considered as clinical failures).
次要结局
- Microbiological eradication(Day 7)
- Resistance emergence(Up to hospital discharge, an average of 1 month)
- Non-ecological adverse events(From the first day of definite therapy to the ToC visit)
- Acquisition of multidrug-resistant bacteria other than DTR P. aeruginosa(Up to hospital discharge, an average of 1 month)
- Clostridioides difficile infection(Up to hospital discharge, an average of 1 month)
- In-hospital death(Up to hospital discharge, an average of 1 month)
- Death at Day 28(Day 28)