An observational study in Bacteremia, sponsored by Hospital Italiano de Buenos Aires. Completed at 16 sites in Argentina. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-11-21.
Sponsored by Hospital Italiano de Buenos Aires · Observational
Ceftazidime-avibactam and aztreonam combination (CAZAVI + ATM) presents a potential alternative for the treatment of metallo-beta-lactamase (MBL)-type carbapenemase-producing Enterobacteriaceae (CPE) bacteremia, particularly where Cefiderocol is not readily available.
This study proposes a Target Trial Emulation (TTE) to assess the efficacy and safety of CAZAVI + ATM compared to other active antibiotics (OAAs) in patients with MBL-type CPE bacteremia, and also to evaluate all-cause 30-day mortality, resistance profiles of isolated microorganisms, clinical failure rates, leukocyte count normalization, adverse events, occurrence of Clostridium difficile infection, and emergence of new multidrug-resistant microorganisms.
Data will be collected through the REDCap database, with rigorous verification for completeness and accuracy.
The outcomes of this project will contribute vital insights into the efficacy and safety of CAZAVI + ATM, informing clinical practice guidelines for the management of MBL-type bacteremia across diverse settings.
Patients will be categorized into two treatment groups for analysis:
CAZAVI + ATM treatment group and Other Active Antibiotics treatment group. As this study is retrospective, treatment group assignment will not be a randomized procedure. Allocation data will be collected from medical records as a dichotomous variable.
In the present study, allocation to CAZAVI + ATM or OAAs will depend on various factors such as drug availability, hospital costs, and medical criteria. Therefore, to ensure comparability among participant characteristics, baseline factors will be adjusted to mitigate indication bias.
To simulate randomization at baseline (identification of MBL-type CPE in blood samples), ensuring comparability between treatment groups, several covariates will be balanced: age, sex, comorbidities (Charlson score), Pitt score, immunosuppression with neutropenia, immunosuppression without neutropenia, days of hospitalization prior to culture, Sequential Organ Failure Assessment (SOFA) score, days of effective antibiotic treatment between blood culture and positivization [25]. Also, as this is a multicenter study, it will be adjusted for the characteristics of the center (public-private), including a total of 10 variables to be adjusted for.
The start of the follow-up period (Time Zero or T0) will be defined by the identification of MBL-type CPE in at least one clinical blood sample (blood culture or PCR). From this point on, all patients will be followed up. A 24-hour grace period will be considered from the identification of MBL-type CPE until the patient initiates either of the two treatment groups.
To mitigate immortality bias, the initiation of both treatment strategies will synchronize with the eligibility criteria at Time Zero of follow-up. Thus, every patient must remain alive from blood culture collection until MBL detection to be eligible for inclusion in the study, and antibiotic treatment must be initiated within 24 hours of detection. All enrolled patients will be followed until 30 days after inclusion in the study, death, or hospital discharge, whichever occurs first.
A sample calculation was performed to test the null hypothesis of equality in the proportion of deaths among patients who received CAZAVI + ATM vs. OAAs. Falcone et al. reported a 19% mortality rate 30 days after inclusion in the CAZAVI + ATM arm and a 44% mortality rate in patients with OAAs. However, for the present study we consider an 80% power is necessary to detect a clinically relevant difference of 15%, therefore we expect a mortality of 34% in the OAAs arm and 19% in the CAZAVI + ATM arm. With an alpha of 5%, two-tailed test, expected ratio CAZAVI + ATM/OAAs of 1:1, a sample size of 270 patients (135 for each branch) is calculated.
Finally, to address indication bias, an adjustment will be made with Propensity Score (PS) matching. Considering 10 confounders entered into the model, at least 10 to 20 events will be required for each variable. Therefore, as the outcome of the PS will be the CAZAVI + ATM exposure variable, at least 150 patients in the CAZAVI + ATM branch will be required. Thus,we consider the calculation of 300 patients, 150 per branch.
A meticulous data collection plan will be carried out to ensure accuracy and confidentiality of the information collected. The following procedures will be implemented:
Data source: Data will be obtained from paper or electronic medical records from each participating center. Patient tracking will be done through the bacteriology records of each hospital center.
Data recording: Variables for each patient will be uploaded to a centralized REDCap database. The principal investigator and associated investigators of each participating center will be responsible for data upload. To maintain privacy and confidentiality, each patient will receive a randomly generated registration number to anonymize their identity in the database.
Data access: Access to center-specific data will be restricted to the principal investigators. Researchers will access REDCap using personal credentials, limiting data access to authorized personnel only.
Confidentiality and anonymization: Adherence to legal provisions, such as the Argentinian National Personal Data Protection (number 25.326) and the Habeas Data, will be strictly complied with in order to protect the confidentiality and privacy of the patients involved in the study. All collected data will be anonymized, devoid of patient identifiers.
Data storage: Once the data upload is completed, the entire database will be stored under password and will only be available to the principal investigators of the study. All necessary precautions will be taken to ensure that the data are maintained in a secure and reliable environment.
The research team is dedicated to upholding data privacy, complying with legal regulations, and conducting the study ethically and responsibly.
322 studies on the registry are indexed under Bacteremia; 49 are open to participants now.
This study's enrollment of 265 is close to the median of 269 across 133 observational studies indexed under Bacteremia.
Browse Bacteremia studies →Hospital Italiano de Buenos Aires is the lead sponsor of 128 studies on the registry; 23 are open to participants now.
Counted across the registry records on this site, refreshed daily.
The study will include a cohort of hospitalized patients from Argentine hospitals. Hospital centers will be invited to participate through the network of the Argentine Society of Medicine (SAM), the Argentine Society of Intensive Care (SATI) and the Argentine Society Of Infectious Diseases (SADI).
Exclusion Criteria:
Bacteremia due to the following complicated infections:
patients who received antibiotic therapy with a standard bacteremia treatment dose of Ceftazidima-Avibactam + Aztreonam (2.5 grams every 8 hours of ceftazidime-avibactam + 2 grams every 8 hours of aztreonam). Dosage adjustments for prolonged infusion or according to renal function will be considered.
Patients who received a combination or at least one of the following antibiotics, with doses adjusted according to renal function: Colistin: 300 mg loading and 150 mg maintenance every 12 hours. Meropenem: 1000 or 2000 mg every 8 hours via infusion in 30 minutes or 3 hours. Fosfomycin: 12 to 24 grams per day, divided every 6 to 8 hours. Aminoglycoside (amikacin: 15 mg/kg/24 hours or gentamicin: 7 mg/kg/24 hours). Tigecycline: 100 or 200 mg loading and 50 or 100 mg maintenance every 12 hours.
All-cause mortality
death from any cause
Time frame: within 30 days from the initiation of treatment (follow-up period)
Describe the resistance profile of the isolated microorganisms
including the associated enzymatic mechanisms
Time frame: 30-day follow-up period
Compare clinical failure
presence of 1) Relapse: recurrent bacteremia due to the same bacteria; 2) Restart of antibiotic therapy targeting the same germs; 3) Local suppurative complication that was not present at the beginning of the infection; 4) Distant complications of the initial infection (defined by the growth of the same bacteria causing the initial bacteremia in distant sites)
Time frame: 30-day follow-up period
Compare the number of days to normalization of the leukocyte count in the laboratory
(leukocyte count less than 12x109/L). (leukocyte co(leukocyte count less than 12x109/L).unt less than 12x109/L)
Time frame: 30-day follow-up period
Compare the proportion of adverse events
including: neutropenia, thrombocytopenia, renal failure, hepatotoxicity, skin reactions and ion-losing tubulopathy
Time frame: 30-day follow-up period
compare the occurrence of Clostridium difficile infection
Appearance of positive C. difficile toxin or positive C. difficile PCR
Time frame: 30-day follow-up period
compare the occurrence of new multidrug-resistant microorganisms
such as KPC, NDM, VIM, IMP, OXA or EVR-producing CLD, detected in both clinical and surveillance samples
Time frame: 30-day follow-up period
Plan to share: No
This study is completed, as verified in Nov 2024. You cannot join it, but the record below documents what was studied.
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Hospital Italiano de Buenos Aires