Real-world Multicentre Study of AZtreonam-AVIbactam Treatment With Infections or Suspected Infections Caused by Multidrug-resistant Gram-negative Bacteria
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Clinical success at the test-of-cure visit (day 7 after completion of initial antibiotic therapy)
研究概览
简要总结
The AZAVI study is a multicenter observational registry (ICU and Infectious Diseases departments), designed to evaluate the real-world use of aztreonam-avibactam for suspected or documented infections caused by metallo-β-lactamase (MBL)-producing Enterobacterales or highly resistant Gram-negative bacteria. The study combines a retrospective cohort (patients treated during the 12 months prior to the drug's hospital availability) and a prospective cohort (patients consecutively included over 24 months).
The primary outcome is clinical success at day 7 after antibiotic discontinuation, defined as resolution of signs and symptoms of infection without recurrence or need for additional active therapy. Secondary outcomes include microbiological eradication, 14-day and 28-day all-cause mortality, infection relapse, length of stay, safety outcomes, and predictors of treatment failure.
Data will be collected using a standardized CRF, including demographics, severity scores, infection site and pathogens, therapeutic regimens, organ failures and support, adverse events, and outcomes. Descriptive statistics and multivariable models will be used to assess real-world effectiveness, identify determinants of clinical response, and inform stewardship strategies. This registry will provide the first national-scale evidence on the role of aztreonam-avibactam in critically ill patients outside the framework of controlled clinical trials.
详细描述
- Background and Rationale The emergence of carbapenemase-producing bacteria, particularly metallo-β-lactamase (MBL) producers such as NDM, poses a major therapeutic challenge in intensive care settings. Current guidelines recommend combining ceftazidime-avibactam (CAZ-AVI) with aztreonam for these infections, but these were developed before the availability of the fixed combination aztreonam-avibactam (ATM-AVI). ATM-AVI offers a more targeted option by pairing a β-lactam stable to MBL hydrolysis with a non-metallo β-lactamase inhibitor. While in vitro and limited in vivo data are promising, real-world evidence remains scarce.
- Objectives
-Primary Objective: To describe the frequency of clinical success of ATM-AVI in patients treated for suspected or documented MBL-producing bacterial infections.
-Secondary Objectives: To assess microbiological and clinical effectiveness. To describe the emergence of resistance during treatment. To identify predictors of clinical and microbiological response. To evaluate ICU and hospital length of stay, mechanical ventilation duration, and all-cause mortality at day 28 and day 90.
To assess safety and adverse events. To compare prescribing practices between infectious diseases and intensive care units. 3. Study Design
Multicenter, observational study with both retrospective and prospective cohorts:
- Retrospective arm: Patients treated with ATM-AVI in the 12 months preceding study initiation.
- Prospective arm: Patients treated with ATM-AVI over a 24-month period following study initiation.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospitalized patients with suspected or documented infection due to MBL-producing bacteria, treated with ATM-AVI.
排除标准
- •Explicit refusal by patient or legal representative.
研究组 & 干预措施
Hospitalized patients under Aztreonam-Avibactam
干预措施: Aztreonam-Avibactam (Drug)
结局指标
主要结局
Clinical success at the test-of-cure visit (day 7 after completion of initial antibiotic therapy)
时间窗: day 7 after completion of initial antibiotic therapy
Clinical success at the test-of-cure visit, day 7 after completion of the initial ATM-AVI regimen, defined as resolution of infection signs and symptoms without need for further active antibiotics. Death (any cause) and microbiologically confirmed relapse are considered treatment failures.
次要结局
- Adverse events attributable to ATM-AVI(Day-28)
- Patterns of monotherapy vs. combination therapy(Day-28)
- Microbiological eradication/persistence(Day-28)
- Mortality(Mortality at day 28 and day 90)
- Duration(Day-28)