An observational study in Enterobacteriaceae Infections, Carbapenem-Resistant Enterobacteriaceae Infection and Immunocompromised Host, sponsored by Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno. Recruiting at 1 site in Argentina. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-22.
Sponsored by Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno · Observational
The goal of this observational study is to learn about the effectiveness and safety of aztreonam-avibactam, an antibiotic used to treat infections caused by highly resistant bacteria, in adults with weakened immune systems.
The main questions this study aims to answer are:
How well does aztreonam-avibactam work in treating these infections?
How many participants recover, and how many die or develop another infection caused by the same bacteria?
What side effects or medical problems occur during or after treatment?
Researchers will also compare participants treated with aztreonam-avibactam with a group of participants previously treated with ceftazidime-avibactam plus aztreonam. This comparison will help researchers understand differences in treatment outcomes.
The study will include adults with weakened immune systems, such as people with cancer, organ transplants, or those receiving medicines that suppress the immune system.
Participants will:
Receive antibiotic treatment chosen by their treating physicians as part of routine medical care.
Have their medical records reviewed to collect information about their infections, treatments, and outcomes.
Be followed for up to 60 days after starting treatment to assess recovery, survival, side effects, and recurrence of infection.
Researchers will not assign treatments or change participants' medical care.
Infections caused by metallo-β-lactamase-producing Enterobacterales (MBL-E) represent a growing clinical challenge, particularly among immunocompromised patients. These individuals are at increased risk of infections caused by multidrug-resistant microorganisms, inappropriate empirical antibiotic treatment, and unfavorable clinical outcomes.
The combination of ceftazidime-avibactam plus aztreonam (CZA-ATM) has demonstrated improved clinical outcomes in patients with MBL-E infections. However, the simultaneous administration of two separate antibiotics presents pharmacokinetic and pharmacodynamic limitations. Aztreonam-avibactam (ATM-AVI), a fixed-dose combination, provides synchronized exposure to both components and improved pharmacokinetic/pharmacodynamic target attainment. Nevertheless, real-world clinical evidence regarding its effectiveness and safety remains limited, particularly in immunocompromised populations.
Study Design
IMMUNO-AVI is an international, multicenter, observational, analytical cohort study involving specialized healthcare centers.
The study aims to provide real-world evidence regarding ATM-AVI use in immunocompromised adults and to inform future treatment decisions for infections caused by MBL-E.
The study uses a mixed time perspective, combining a prospective cohort of participants treated with aztreonam-avibactam and a retrospective historical comparison cohort of participants treated with ceftazidime-avibactam plus aztreonam. Both cohorts will be evaluated using standardized study definitions to allow comparative analyses.
Treatment decisions are made independently by the treating physicians. The study does not assign antimicrobial treatments or modify routine patient care.
Data Collection and Follow-up
Clinical and microbiological information will be collected using standardized electronic case report forms through Research Electronic Data Capture (REDCap).
Collected information will include demographic characteristics, underlying diseases, immunocompromising conditions, previous healthcare exposures, risk factors for multidrug-resistant infections, infection characteristics, severity of illness, microbiological findings, antimicrobial susceptibility, treatment regimens, and clinical outcomes.
Microbiological identification and antimicrobial susceptibility testing will follow validated local laboratory procedures. Carbapenemase production and resistance mechanisms will be characterized using available phenotypic and molecular methods.
Participants in the prospective cohort will be followed for up to 60 days after treatment initiation. Clinical response, treatment outcomes, mortality, infection recurrence, and potential treatment-related adverse events will be assessed at predefined time points.
Quality Assurance, Data Validation, and Study Monitoring
A centralized quality assurance plan will be implemented to ensure the accuracy, completeness, consistency, and reliability of data collected across participating centers. Standardized electronic case report forms (eCRFs) will be used through Research Electronic Data Capture (REDCap), with predefined study variables and operational definitions.
Data Quality Checks
Data validation procedures will include:
Identified inconsistencies will be reviewed and addressed through communication with the corresponding participating centers.
Study Monitoring and Quality Control
Data will be entered locally by authorized study personnel and monitored centrally to promote consistency across participating institutions.
Quarterly quality assessments will review recruitment performance, completeness of key variables, and adherence to predefined follow-up assessments at day 7, end of treatment, day 30, and day 60.
A midpoint interim assessment will evaluate overall recruitment, data completeness, and potential deviations from protocol definitions. These assessments will be descriptive and will not involve formal hypothesis testing or changes to study procedures.
Before final statistical analysis, the database will undergo cleaning and validation to identify unresolved inconsistencies and assess overall data quality.
Statistical Analysis
Descriptive analyses will summarize baseline characteristics, clinical presentation, antimicrobial treatment, effectiveness, and safety outcomes.
Comparative analyses will evaluate differences between the prospective ATM-AVI cohort and the historical CZA-ATM cohort. Multivariable logistic regression and time-to-event analyses, including Kaplan-Meier estimates and Cox proportional hazards models, will be used as appropriate.
To address potential confounding, inverse probability of treatment weighting (IPTW) based on propensity scores will be applied. Covariate balance will be assessed using standardized mean differences.
Additional analyses will examine clinically relevant subgroups, including neutropenic and non-neutropenic participants, solid organ and hematopoietic stem cell transplant recipients, and participants with bacteremic and non-bacteremic infections.
Sample Size Calculation
Based on the historical case volume at participating centers, a minimum of 200 participants is expected to be enrolled in the prospective aztreonam-avibactam (ATM-AVI) cohort, allowing a descriptive assessment of clinical effectiveness and safety outcomes.
For the comparative analysis, the sample size was calculated assuming a mortality rate of 20% in the historical ceftazidime-avibactam plus aztreonam (CZA-ATM) cohort and an expected mortality rate of 12% in the ATM-AVI cohort, corresponding to a 40% relative reduction and an 8-percentage-point absolute difference.
Using a two-sided significance level of 0.05, 80% statistical power, and a 1:2 allocation ratio between the ATM-AVI and CZA-ATM cohorts, the estimated sample size was 732 evaluable participants (244 in the ATM-AVI cohort and 488 in the CZA-ATM cohort).
Allowing for up to 10% of participants with incomplete data, loss to follow-up, or non-evaluable outcomes, the anticipated total enrollment is approximately 814 participants, including 271 in the prospective ATM-AVI cohort and 543 in the retrospective CZA-ATM cohort.
57 studies on the registry are indexed under Enterobacteriaceae Infections; 13 are open to participants now.
This study's planned enrollment of 814 is above the median of 300 across 27 observational studies indexed under Enterobacteriaceae Infections.
Browse Enterobacteriaceae Infections studies →Centro de Educación Medica e Investigaciones Clínicas Norberto Quirno is the lead sponsor of 8 studies on the registry; 1 is open to participants now.
Counted across the registry records on this site, refreshed daily.
The study population consists of immunocompromised adults with microbiologically confirmed infections caused by metallo-β-lactamase-producing Enterobacterales receiving care at participating referral hospitals in Europe and the Americas. The prospective cohort will include participants treated with aztreonam-avibactam as part of routine clinical care. The retrospective historical comparison cohort will include participants previously treated with ceftazidime-avibactam plus aztreonam. Eligible participants will be identified through routine clinical and microbiological records and included consecutively at participating centers. Treatment decisions are made independently of study participation.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Participants must meet at least one of the following immunocompromising conditions:
Exclusion Criteria:
Positive microbiological specimens that do not represent a true infection, including:
Prospective cohort of immunocompromised adults with microbiologically confirmed monomicrobial infections caused by metallo-β-lactamase-producing Enterobacterales (MBL-E) who receive definitive treatment with aztreonam-avibactam (ATM-AVI) for at least 72 hours. Antibiotic treatment is selected by the treating physician independently of study participation. Clinical and microbiological data will be collected prospectively, and participants will be followed for up to 60 days after treatment initiation to assess clinical effectiveness, safety, mortality, and infection relapse.
Drug: Aztreonam-Avibactam
Retrospective historical comparison cohort of immunocompromised adults with microbiologically confirmed monomicrobial infections caused by metallo-β-lactamase-producing Enterobacterales (MBL-E) who received definitive treatment with ceftazidime-avibactam plus aztreonam (CZA-ATM) for at least 72 hours. Treatment was prescribed as part of routine clinical care, independently of the study. Clinical, microbiological, treatment, and outcome data will be collected retrospectively from existing medical records using standardized study definitions.
Drug: Ceftazidime-Avibactam Plus Aztreonam
Aztreonam-avibactam (ATM-AVI) administered as definitive antimicrobial treatment for infections caused by metallo-β-lactamase-producing Enterobacterales. Treatment is prescribed as part of routine clinical care, independently of study participation. Dose, administration interval, infusion duration, and treatment duration are determined by the treating physician.
Drug page: Aztreonam
Ceftazidime-avibactam administered in combination with aztreonam as definitive antimicrobial treatment for infections caused by metallo-β-lactamase-producing Enterobacterales. Treatment was prescribed as part of routine clinical care, independently of study participation. Treatment information will be obtained retrospectively from existing medical records.
All-Cause Mortality at Day 30
Proportion of participants who die from any cause within 30 days after initiation of aztreonam-avibactam (ATM-AVI) or ceftazidime-avibactam plus aztreonam (CZA-ATM), regardless of the cause of death.
Time frame: Within 30 days after treatment initiation
Favorable Clinical Response at Day 7
Proportion of participants with a favorable clinical response, defined as the absence of fever and hypotension, together with improvement in the signs and symptoms of the index infection.
Time frame: Day 7 after treatment initiation
Clinical Cure at the End of Treatment
Proportion of participants achieving clinical cure, defined as resolution of fever and hypotension for at least 72 hours, together with resolution of the signs and symptoms of the index infection. The end of treatment corresponds to completion of all antimicrobial treatment directed at the infectious episode.
Time frame: At completion of antimicrobial treatment for the index infection
Microbiological Cure
Proportion of evaluable participants with documented conversion of cultures from the index infection site to negative. Assessment will be based on follow-up cultures obtained as part of routine clinical care.
Time frame: From treatment initiation through the end of treatment
All-Cause Mortality at Day 7
Proportion of participants who die from any cause within 7 days after initiation of ATM-AVI or CZA-ATM treatment.
Time frame: Within 7 days after treatment initiation
Infection-Related Mortality at Day 7
Proportion of participants who die within 7 days after treatment initiation in the presence of microbiological, histological, or clinical evidence of active infection, after excluding alternative causes of death.
Time frame: Within 7 days after treatment initiation
Infection-Related Mortality at Day 30
Proportion of participants who die within 30 days after treatment initiation in the presence of microbiological, histological, or clinical evidence of active infection, after excluding alternative causes of death.
Time frame: Within 30 days after treatment initiation
Infection Relapse Within 60 Days
Proportion of participants experiencing recurrence of infection caused by the same microorganism responsible for the index infection within 60 days after initiation of ATM-AVI or CZA-ATM treatment.
Time frame: Within 60 days after treatment initiation
Incidence of Hematological Abnormalities
Proportion of participants developing hematological abnormalities, including leukopenia (leukocyte count below 4,000/mm³), neutropenia (neutrophil count below 1,000/mm³), eosinophilia (eosinophil count above 500/mm³), thrombocytopenia (platelet count below 150,000/mm³), or anemia according to institutional reference ranges.
Time frame: During treatment and up to 30 days after treatment completion
Incidence of Hepatic Toxicity
Proportion of participants developing hepatic toxicity, defined as ALT or AST above the upper limit of normal (ULN). Hepatitis is defined as transaminase elevation at least 5 times the ULN, or at least 3 times the ULN accompanied by symptoms such as abdominal pain, nausea, or vomiting.
Time frame: During treatment and up to 30 days after treatment completion
Incidence of Acute Kidney Injury
Proportion of participants developing acute kidney injury, defined as an increase in serum creatinine of at least 0.3 mg/dL or at least 1.5 times baseline, or urine output below 0.5 mL/kg/hour for at least 6 hours.
Time frame: During treatment and up to 30 days after treatment completion
Incidence of Allergic Reactions
Proportion of participants experiencing allergic reactions, including rash, angioedema, anaphylaxis, or severe cutaneous reactions such as erythema multiforme or toxic epidermal necrolysis.
Time frame: During treatment and up to 30 days after treatment completion
Incidence of Gastrointestinal Symptoms
Proportion of participants experiencing diarrhea and/or vomiting during the safety assessment period.
Time frame: During treatment and up to 30 days after treatment completion
Incidence of Neuropsychiatric Symptoms
Proportion of participants experiencing delirium, encephalopathy, or dysgeusia during the safety assessment period.
Time frame: During treatment and up to 30 days after treatment completion
Incidence of Clostridioides difficile Infection
Proportion of participants developing Clostridioides difficile infection, defined as at least 3 unformed stools within 24 hours without an alternative explanation, together with microbiological evidence of toxigenic C. difficile by toxin detection or molecular testing.
Time frame: During treatment and up to 30 days after treatment completion
Plan to share: Yes — De-identified individual participant data underlying the results reported in the final publication may be made available to qualified researchers upon reasonable request to the study coordinating team. Shared data may include relevant demographic, clinical, microbiological, treatment, and outcome variables, together with an accompanying data dictionary. Data sharing will be subject to scientific review, applicable ethical approvals, participant confidentiality safeguards, and institutional and national data protection regulations. Direct personal identifiers will not be shared.
Supporting information: Study protocol, Statistical analysis plan
Time frame: Data will be available beginning 12 months after publication of the main study results and will remain available for 5 years.
Access criteria: Qualified researchers may submit a scientifically justified request to the study coordinating team, including a research proposal, planned analyses, and intended data use. Requests will be reviewed for scientific merit, methodological appropriateness, and compliance with applicable ethical and data protection requirements. Approved requests will require a data use agreement specifying confidentiality, data security, and permitted uses. Data will be transferred through a secure mechanism.
No publications or documents are linked to this record.
Started Oct 2026 (actual). Primary completion is estimated for Nov 2028, 24 months after the start.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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