Clinical trial NCT04167228: Impact of Ceftazidime / Avibactam Treatment vs Better Available Therapy on Mortality of Patients With Infections Caused by Carbapenem-resistant Enterobacteria
Official title: Impact of Ceftazidime / Avibactam Treatment vs Better Available Therapy on Mortality of Patients With Infections Caused by Carbapenem-resistant Enterobacteria
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Carbapenem-Resistant Enterobacteriaceae Infection
Keywords: ceftazidime / avibactam
carbapenem resistant enterobacteria
Lead sponsor: Maimónides Biomedical Research Institute of Córdoba
Sponsor class: OTHER
First posted: 2019-11-18
Enrollment: 348
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with infections caused by carbapenem resistant enterobacteria

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 30-day mortality rate
timeFrame: At day 30 after the start of the treatment
measure: Clinical response on day 21
timeFrame: At day 21 after the start of the treatment
Secondary outcomes:
measure: Microbiological response
timeFrame: At day 30 after the start of the treatment
measure: 30-day mortality rate in the group of patients with caz-avi in monotherapy and in the group with combined therapy with caz-avi
timeFrame: At day 30 after the start of the treatment
measure: Risk factors associated with the development of resistance to ceftazidime-avibactam during treatmen
timeFrame: At day 30 after the start of the treatment
measure: Duration of hospital stay after infection
timeFrame: At day 30 after the start of the treatment
measure: Duration of antibiotic treatment during the episode
timeFrame: At day 30 after the start of the treatment
measure: Recurrence
timeFrame: At day 30 after the start of the treatment
measure: Safety evaluation of the treatment
timeFrame: At day 30 after the start of the treatment
Other outcomes:
Locations:
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Universitario de Bellvitge
state: Barcelona
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria "Dr. Negrín"
state: Canary Islands
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: Coruña
city: Vigo
country: Spain
facility: Hospital Álvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Barcelona
country: Spain
facility: Hospital Clínico de Barcelona
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
Study officials:
affiliation: Hospital Universitario Reina Sofía
name: Juan José Castón Osorio, MD
role: PRINCIPAL_INVESTIGATOR
References: