Impact of Ceftazidime / Avibactam Treatment vs Better Available Therapy on Mortality of Patients With Infections Caused by Carbapenem-resistant Enterobacteria

Study Overview
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Brief Summary
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Patients with infections caused by carbapenem-resistant enterobacteria treated with CAZ-AVI versus patients treated with BAT are compared. The BAT group includes fosfomycin, tigecycline, gentamicin, meropenem and colistin.

Detailed Description
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Carbapenem-resistant enterobacteria (CRE) are a public health problem. The morbidity and mortality of patients with invasive infections due to CRE are high. The best treatment is unknown, however, combination therapy with at least 2 active drugs is often recommended for high-risk patients, and monotherapy is probably not inferior to this in low-risk patients. Ceftazidime-avibactam is active against many CRE, and in some countries it has been prescribed under compassionate use programs for these infections; It has recently been approved by the FDA and the EMA for specific indications. Recent data suggest that ceftazidime-avibactam may be superior for the treatment of infections caused by sensitive CRE, rather than traditional regimens that often include colistin, usually combined with other drugs. However, these studies include a low number of patients and are subject to important biases. Additionally, the development of resistance to this drug during / after treatment has been described and is worrying.

Official Title
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Impact of Ceftazidime / Avibactam Treatment vs Better Available Therapy on Mortality of Patients With Infections Caused by Carbapenem-resistant Enterobacteria

Conditions
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Carbapenem-Resistant Enterobacteriaceae Infection

Intervention / Treatment
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* Drug: Ceftazidime-Avibactam
* Drug: Best Available Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with complicated urinary tract infections, nosocomial pneumonia (including pneumonia associated with ventilation), complicated intra-abdominal infections or bacteremia (if the focus of infection is any of the above, the patient should be included in both groups) due to CRE, treated > 2 days with ceftazidime-avibactam. Patients with bacteremia can be included in one of the other cohorts if the focus of the infection is the urinary tract, respiratory tract or an intra-abdominal infection and they meet the appropriate criteria (see below). The retrospective design of this study has been carried out to avoid the induction of the prescription of ceftazidime-avibactam in each center. For this, patients will be included at the end of the period of evaluation of the primary objective (crude mortality at day 30). If more than one patient can be used as a control, the one with the closest admission date will be chosen. Control: local historical cohort - Patients treated with ceftazidime-avibactam will be compared with patients treated with BAT. Because after approval of the use of ceftazidime-avibactam, BAT could be used less frequently to treat this type of infection, patients treated with BAT from January 1, 2014 will be included. These patients will be matched by hospital, type of hospital. infection (urinary tract vs others) and INCREMENT score. Exclusion Criteria: The infection is considered polymicrobial according to the standard microbiological interpretation of the crop results (except for complicated intra-abdominal infections, in which case, polymicrobial infections are allowed). Patients with infections caused by CRE without susceptibility to ceftazidime-avibactam. The patient is participating in a clinical trial that involves active treatment for infections. Patients with cardiopulmonary no resuscitation order or with a life expectancy < 30 days.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CRE infected patients treated with ceftazidime-avibactam<br>Patients with infections caused by carbapenem resistant enterobacteria treated with ceftazidime-avibactam | Drug: Ceftazidime-Avibactam<br>* Patients with complicated urinary tract infections, nosocomial pneumonia (including pneumonia associated with ventilation), complicated intra-abdominal infections or bacteremia (if the focus of infection is any of the above, the patient should be included in both groups) due to CRE, treated > 2 days with ceftazidime-avibactam.<br>|
| CRE infected patients treated with best available treatment<br>Patients with infections caused by carbapenem resistant enterobacteria treated with the best available treatment | Drug: Best Available Therapy<br>* Patients with complicated urinary tract infections, nosocomial pneumonia (including pneumonia associated with ventilation), complicated intra-abdominal infections or bacteremia (if the focus of infection is any of the above, the patient should be included in both groups) due to CRE, treated > 2 days with the best available treatment other than ceftazidime-avibactam.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30-day mortality rate | To describe the 30-day mortality rate in the caz-avi group and in the group with the best available therapy of patients with infections caused by carbapenem-resistant enterobacteria. | At day 30 after the start of the treatment | 
| Clinical response on day 21 | To describe the clinical response on day 21 of the caz-avi group and in the group with the best available therapy of patients with infections caused by carbapenem-resistant enterobacteria. | At day 21 after the start of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological response | Microbiological response in the Test-of-cure, categorized as eradication, microbiological failure or uncertain. | At day 30 after the start of the treatment | 
| 30-day mortality rate in the group of patients with caz-avi in monotherapy and in the group with combined therapy with caz-avi | Describe the 30-day mortality rate in the group of patients with caz-avi in monotherapy and in the group with combined therapy with caz-avi, who present with infections caused by carbapenem-resistant enterobacteria. | At day 30 after the start of the treatment | 
| Risk factors associated with the development of resistance to ceftazidime-avibactam during treatmen | Describe the rates and risk factors associated with the development of resistance to ceftazidime-avibactam (MIC> 8 microg / mL) during treatment | At day 30 after the start of the treatment | 
| Duration of hospital stay after infection | Number of days elapsed from the end of antibiotic treatment until discharge and duration of ICU stay if appropriate. | At day 30 after the start of the treatment | 
| Duration of antibiotic treatment during the episode | Number of days of antibiotic treatment during the episode | At day 30 after the start of the treatment | 
| Recurrence | Reappearance of the infection according to the same criteria and by the same microorganism | At day 30 after the start of the treatment | 
| Safety evaluation of the treatment | Number of adverse reactions related to therapy | At day 30 after the start of the treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ceftazidime / avibactam, carbapenem resistant enterobacteria