Mortality of MBL-producing Enterobacteriaceae Bacteremias with the Combined Use of Ceftazidime-avibactam and Aztreonam Vs. Other Active Antibiotics. a Multicenter Target Trial Emulation.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 265
- 试验地点
- 16
- 主要终点
- All-cause mortality
研究概览
简要总结
Ceftazidime-avibactam and aztreonam combination (CAZAVI + ATM) presents a potential alternative for the treatment of metallo-beta-lactamase (MBL)-type carbapenemase-producing Enterobacteriaceae (CPE) bacteremia, particularly where Cefiderocol is not readily available.
This study proposes a Target Trial Emulation (TTE) to assess the efficacy and safety of CAZAVI + ATM compared to other active antibiotics (OAAs) in patients with MBL-type CPE bacteremia, and also to evaluate all-cause 30-day mortality, resistance profiles of isolated microorganisms, clinical failure rates, leukocyte count normalization, adverse events, occurrence of Clostridium difficile infection, and emergence of new multidrug-resistant microorganisms.
Data will be collected through the REDCap database, with rigorous verification for completeness and accuracy.
The outcomes of this project will contribute vital insights into the efficacy and safety of CAZAVI + ATM, informing clinical practice guidelines for the management of MBL-type bacteremia across diverse settings.
详细描述
Patients will be categorized into two treatment groups for analysis:
CAZAVI + ATM treatment group and Other Active Antibiotics treatment group. As this study is retrospective, treatment group assignment will not be a randomized procedure. Allocation data will be collected from medical records as a dichotomous variable.
In the present study, allocation to CAZAVI + ATM or OAAs will depend on various factors such as drug availability, hospital costs, and medical criteria. Therefore, to ensure comparability among participant characteristics, baseline factors will be adjusted to mitigate indication bias.
To simulate randomization at baseline (identification of MBL-type CPE in blood samples), ensuring comparability between treatment groups, several covariates will be balanced: age, sex, comorbidities (Charlson score), Pitt score, immunosuppression with neutropenia, immunosuppression without neutropenia, days of hospitalization prior to culture, Sequential Organ Failure Assessment (SOFA) score, days of effective antibiotic treatment between blood culture and positivization [25]. Also, as this is a multicenter study, it will be adjusted for the characteristics of the center (public-private), including a total of 10 variables to be adjusted for.
The start of the follow-up period (Time Zero or T0) will be defined by the identification of MBL-type CPE in at least one clinical blood sample (blood culture or PCR). From this point on, all patients will be followed up. A 24-hour grace period will be considered from the identification of MBL-type CPE until the patient initiates either of the two treatment groups.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Retrospective
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 aged 18 years or older
- •Confirmed bacteremia by MBL-type Carbapenemase-Producing Enterobacteriaceae (CPE)
- •Initiation of effective antibiotic therapy within 24 hours of identification of MBL-type CPE and within 96 hours of blood sample.
排除标准
- •Bacteremia due to the following complicated infections:
- •Endocarditis or other endovascular infection without extractable focus.
- •Necrotizing fasciitis
- •Osteomyelitis or septic arthritis
- •Confirmed prostatitis
- •Non-drainable abscess or other unresolved infection requiring surgical intervention (e.g., cholecystitis)
- •Central nervous system infections
- •Successive episodes of bacteremia by the same pathogen (with the same resistance profile) within the previous 60 days.
- •Polymicrobial bacteremias, not classified as contaminants.
- •Patients with documented allergy to beta-lactams.
结局指标
主要结局
All-cause mortality
时间窗: within 30 days from the initiation of treatment (follow-up period)
death from any cause
次要结局
- Describe the resistance profile of the isolated microorganisms(30-day follow-up period)
- Compare clinical failure(30-day follow-up period)
- compare the occurrence of Clostridium difficile infection(30-day follow-up period)
- compare the occurrence of new multidrug-resistant microorganisms(30-day follow-up period)
- Compare the number of days to normalization of the leukocyte count in the laboratory(30-day follow-up period)
- Compare the proportion of adverse events(30-day follow-up period)
研究者
Mariana Vaena
MD
Hospital Italiano de Buenos Aires