Zavicefta® Use Patterns, Effectiveness and Safety – EZTEAM Study
Research type
Research Study
Full title
Real-World Observational Study of Zavicefta® (ceftazidime-avibactam) to Characterize Use Patterns, Effectiveness and Safety – EZTEAM Study
IRAS ID
249910
Contact name
Anita Verma
Contact email
Sponsor organisation
Pfizer Inc.
Duration of Study in the UK
1 years, 0 months, 0 days
Research summary
Summary of Research
The aim of this study is to provide insights about the Use Patterns, Effectiveness and Safety of Zavicefta. Zavicefta is a unique combination of two antibiotics called ceftazidime and avibactam, and was developed to treat bacterial infection caused by gram-negative bacteria. In the UK Zavicefta is approved for the treatment of complicated intra-abdominal infection (cIAI), complicated urinary tract infections (cUTIs), hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP), and infection due to aerobic gram-negative organisms with limited treatment options. This study will collect real world information about Zavicefta in approximately 8 countries and identify approximately 400 evaluable patients.\n\nThis observational study will enrol adult patients who have been hospitalised and treated with Zavicefta. Patients will be identified over a 12-month period and information about their treatment will be recorded from their medical records. Patients will be followed from Zavicefta initiation until either 60 days after they are discharged from hospital, the patient dies, withdraws from the study, or is loss-to-follow-up, whichever occurs first.\nAs the study is observational, it involves a retrospective chart review and therefore participating patients will not undergo any study related procedures or have any scheduled visits. Rather, data that is already available as part of standard care will be collected. Data will be abstracted from medical records using an electronic case report form (eCRF). Baseline data will include patient sociodemographic, clinical, and treatment characteristics and follow-up data will include details of treatment over time and clinical, microbiological, and healthcare resource utilisation outcomes.Summary of Results
Setting: 572 eligible patients were enrolled at 29 European sites (including Austria, France, Germany, Greece, Italy, Spain, the United Kingdom, and Russian Federation) and 15 Latin American (LATAM) sites (Argentina, Brazil, Colombia).Variables and data sources: Data collected included patient characteristics, clinical and microbiological characteristics of the infection, treatment patterns, effectiveness, and safety of ceftazidime-avibactam, medical resource utilization during the hospital stay, mortality and hospital readmissions up to 60 days post discharge or a censoring event.
Results: From 572 patients enrolled, 516 (90.2%) patients were treated for ≥72 hours, including 354 patients from the European region and 162 patients from the LATAM region. Patients were in majority males (68.2%), and their median age was 62 years; approximately 45% of patients were distributed in the 60-69 and 70-79 age classes. The mean Deyo-Charlson Comorbidity score was 4.6. A substantial proportion of patients had conditions associated with immune deficiency, such as hematological malignancies, bone marrow or solid organ transplant.
Infection sources identified were intra-abdominal, urinary, respiratory, bloodstream infection/sepsis, and other indications (approximately 20% each); 26.0% of the patients presented a secondary bacteremia. Klebsiella pneumoniae was the most common bacteria identified in the latest microbiological evaluation before the start of ceftazidime-avibactam (60%). Resistance of isolates tested was mainly expressed against penicillins/beta-lactamase inhibitor (85%), cephalosporins (82-83%), carbapenems (75-78%), and fluoroquinolones (75%). Two-thirds of bacteria tested for susceptibility were MDR (with 92-98% of resistance to penicillins/beta-lactamase inhibitor, cephalosporins, carbapenems and fluoroquinolones), with the highest proportion in patients with urinary infection. Without prior exposure, 5.5% and 9.9% of isolates (mostly from the genus Klebsiella) were found resistant to ceftazidime-avibactam at 2 sample times.
Ceftazidime-avibactam was mainly used as second line treatment, and in combination with other antibiotics (69.4%; notably with aztreonam); the daily dose, frequency and duration of infusion were according to the approved prescribing information. Treatment success was achieved in 77.3% of patients overall (88.3% amongst patients with urinary infection). In-hospital mortality rate was 23.1%. Adverse experience collected from hospital records was uncommon.Discussion: In complement to other real-world evidence reports, this study provides important evidence on treatment patterns, effectiveness, and safety of ceftazidime-avibactam in routine clinical practice, by its recruitment across 11 countries from Europe and LATAM regions and the high proportion of patients treated for bloodstream infection and other indications.
REC name
London - South East Research Ethics Committee
REC reference
18/LO/2035
Date of REC Opinion
26 Nov 2018
REC opinion
Favourable Opinion