Ceftazidime-Avibactam Use in Critically Ill Patients With Carbapenem-Resistant Enterobacteriaceae Infections (AVI-ICU)
Carbapenem-Resistant Enterobacteriaceae Infection
About this trial
This is an interventional treatment trial for Carbapenem-Resistant Enterobacteriaceae Infection focused on measuring Carbapenem-Resistant Enterobacteriaceae, Critically ill, Ceftazidime-avibactam, Colistin
Eligibility Criteria
Inclusion Criteria:
- Patients aged ≥ 18 years.
- Admitted to an intensive care unit (ICU).
- Patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP), complicated urinary tract infection (cUTI), bacteremia, complicated intraabdominal infection (cIAI), and complicated skin and soft tissue infection (cSSTI).
- Confirmed infection with CRE, based on a culture and sensitivity obtained within the past 72 hours of study enrollment.
- Suspected CRE infection according to one of the following: (1) positive Xpert Carba-R test screening for blaKPC or blaOXA-48 or blaNDM or blaVIM or blaIMI assessed on the admission to the ICU, (2) positive culture for CRE obtained within 3 months from time of enrollment.
Exclusion Criteria:
- Acute Physiology and Chronic Health Evaluation II (APACHE II) score more than 30
- known significant hypersensitivity reaction to beta-lactam antibiotics or colistin
- Positive culture for Stenotrophomonas maltophilia or Acinetobacter baumannii within the current hospitalization.
- Patients received the study intervention or control for more than 24 hours before the intended randomization.
- Patient/substitute decision-maker or caring physician's refusal to enroll in the study.
- Patient with concomitant suspected or confirmed meningitis.
- Pregnancy.
- Cystic fibrosis.
- Patients with Do Not Attempt to Resuscitate (DNAR) code status.
- Prior knowledge that the index CRE pathogen was resistant to colistin (MIC >2 μg/ml) or ceftazidime-avibactam (MIC > 8 μg/ml) before randomization.
- Objective clinical evidence for any of the following infections that necessitate study therapy for >14 days: endovascular infection, including endocarditis, osteomyelitis, prosthetic joint infection, meningitis, and/or other central nervous system infections
Sites / Locations
- King Faisal Specialist Hospital & Research CentreRecruiting
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Ceftazidime-avibactam
Colistin
Ceftazidime-avibactam 2.5 grams intravenous (IV) every 8 hours infused over two hours for a duration of 7-14 days, with dose adjustment for renal impairment according to the FDA prescribing information. Patients who have a positive Xpert Carb-R screening test or culture for CRE with metallo-beta-lactamases will receive aztreonam added to ceftazidime-avibactam.
Colistin (9-million-unit loading dose IV followed with 9 million units IV daily divided into 3 doses), for 7 to 14 days. Patients with renal impairment will receive antibiotics with adjusted doses based on their glomerular filtration rate or the use and type of renal replacement therapy according to the 2019 International Consensus Guidelines for the Optimal Use of the Polymyxins.