Prospective Observational Study to Assess the Risk Factors, Clinical Management and Outcomes of Hospitalized Patients With Serious Infections Caused by Carbapenem-resistant Enterobacteriaceae and Acinetobacter Baumannii
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 2,515
- 试验地点
- 50
- 主要终点
- Mortality
研究概览
简要总结
Among antibiotic-resistant organisms, the Gram-negative bacteria are now the most important challenge because of the rapid worldwide spread of mechanisms conferring resistance to multiple drugs. The most recent and worrying problem is the emergence and spread of carbapenemases. Additionally, carbapenem-resistance is known to be very frequent among Acinetobacter baumannii isolates for many years. Overall, the therapeutic options available against carbapenem-resistant Enterobacteriaceae (CRE) and A. baumannii (CRAB) are very limited. The best available treatment (BAT) against CRE is unknown, which is a challenge for therapeutic decisions and also for the design of randomized trials with new drugs. The generic objectives of EURECA are to obtain high-quality observational data to inform the design of randomized controlled trials for complicated intraabdominal infections, pneumonia, complicated urinary tract infections and bloodstream infections due to Carbapenem-resistant Enterobacteriaceae (CRE) and carbapenem-resistant Acinetobater baumannii, and to provide cohort data that could eventually be used as historical controls for future comparisons with new drugs targeting CRE. This will be achieved by a prospective, multinational cohort study of patients with targeted infections due to CRE and CRAB, and by matched case-control-control studies.
详细描述
HYPOTHESIS:
H1: 5 independent predictors for cure and mortality can be identified, including active empirical therapy, early targeted optimized therapy and early source management if needed.
H2: For pneumonia, cIAI (complicated intrabdominal infection) and BSI (bloodstream infection), combination therapy with two active drugs, one of them being (if available) an "active" beta-lactam (such as meropenem or imipenem if minimum inhibitory concentration [MIC] <16 mg/L, aztreonam if isolate is susceptible as in many metallo-beta-lactamase producers, or cephalosporin if isolate is susceptible as in some OXA-48 producers). For cUTI (complicated urinary tract infection), monotherapy with an "active" beta-lactam as above, colistin or an aminoglycoside (if active in vitro) is as effective as combination therapy.
H3. Clinical cure rate at test of cure (TOC) will be 50% with BAT. H4: Specific carbapenemase types do not independently influence cure rate or mortality.
H5: CRE infections caused by isolates showing a carbapenem MIC <16 mg/L are associated with higher probability of cure and lower mortality.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •The infection is considered to be polymicrobial according to standard microbiological interpretation of culture results (except for cIAI, in which polymicrobial infections are allowed).
- •The patient was participating in a clinical trial that involved active treatment for the infections.
- •The patient was previously included in the same cohort of this study for the same organism. A single episode of CRE or CRAB per patient can be included. Patients who suffer a CRE infection could later be included in the CRAB cohort if developing a CRAB infection and vice versa.
- •Patients with do not resuscitate orders or with a life expectancy of <30 days. Selection criteria for CSE GROUP Inclusion criteria (all must be fulfilled)
- •Isolation of CSE from a clinical sample (e.g., a sample obtained in the work-up of a patient with suspicion of infection; therefore, screening samples are not considered).
- •The patient meets the criteria for any of the following infections (see definitions below): complicated urinary tract infection, pneumonia, intraabdominal infection or bloodstream infection (if the source of infection is any of the above, the patient will be included in both groups).
- •The infection is the same as that of the index case; in case of BSI, the source of bacteraemia must be the same as the index case classified as follows: UTI, pneumonia, intraabdominal infection or any other.
- •The type of acquisition is the same as for the index CRE case (nosocomial or community).
- •The previous length of hospitalization before the infection onset is minus 1 up to minus 3 days the previous length of hospitalization before the CRE infection date in the CRE correspondent (up to minus 7 days if the CRE case occurred after 14 days of previous stay).
- •The patient was admitted to the same type of service as the index case (medical, surgical, ICU, neonatal Unit, paediatric ICU, general paediatric wards).
- •Patient or his/her representative sign the inform consent (if requested by local IRB).
- •Patients in this group will be included until the needed sample size is reached.
- •Exclusion criteria
- •The infection is considered to be polymicrobial according to standard microbiological interpretation of culture results (except for cIAI, in which polymicrobial infections are allowed).
- •Patient is participating in a clinical trial that involved active treatment for the infections at assessment.
- •Patients with do not resuscitate orders or with a life expectancy of <30 days. The first patient found with all inclusion criteria and no exclusion criteria will be included.
- •Selection criteria for ADMITTED CONTROL GROUP Inclusion criteria (all must be fulfilled)
- •Patient is admitted in the same hospital ward where was admitted the index CRE.
- •The previous length of hospitalization is at least one day less than the previous duration of hospitalisation of the correspondent CRE case when the CRE infection occurred.
- •Patient or his/her representative sign the inform consent (if requested by local IRB).
- •Patients in this group will be included until the needed sample size is reached.
- •Exclusion criteria
- •Patient was participating in a clinical trial that involved active treatment for the infections at assessment.
- •Patients with do not resuscitate orders or with a life expectancy of <30 days.
- •Because the search for CSE controls is more difficult, the search for admitted control patients can be started once a CSE control has been included; the first 3 patients with the above inclusion criteria and no exclusion criteria will be included.
结局指标
主要结局
Mortality
时间窗: 30 days
Death by any caused
Clinical response (failure vs cure or improvement)
时间窗: 21 days
Clinical failure: non-improvement or deterioration (clinical situation qualified as similar or worse in comparison to that at the diagnosis of bacteremia), death (death of the patient for whatever the reason) or relapse (reappearance of signs and symptoms related to the infection, after the end of treatment). Clinical cure: resolution of all signs and symptoms related to the infection, and antibiotic therapy is no longer necessary. Clinical improvement: resolution or partial improvement of signs or symptoms of the infection at the time of assessment but antibiotic therapy is still needed. TOC was decided at day 21 because it is usually 7 days after the expected average duration of therapy, which is around 10-14 days for the infections included.
Infection due to CRE
时间窗: 1 year
Infection due to CRE (study 2)
Length of hospital stay.
时间窗: 1 year
Duration of hospitalisation (study 3)
次要结局
- Microbiological response (microbiological eradication, failure or uncertain).(21 days)
- Infection-related mortality(30 days)
- Length of hospital stay after the infection (and ICU stay, mechanical ventilation if appropriate).(After end of hospitalisation)
- Superinfection(30 days)
- Therapy-related adverse events.(30 days)
- Mortality during hospitalisation.(1 year)
- Duration of antibiotic treatment for the episode.(30 days)
- Recurrence(30 days)