Mortality of MBL-producing Enterobacteriaceae Bacteremias with the Combined Use of Ceftazidime-avibactam and Aztreonam Vs. Other Active Antibiotics. a Multicenter Target Trial Emulation.

NCT06419296 | Completed

• 1 other identifier: 6915
• Study Type: observational
• Target: 265
• Locations: 1 country
• Sites: 16

Brief Summary

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.

Conditions

Bacteremia

Keywords

multicenter; target trial emulation; bacteremia; metallo-beta-lactamase; carbapenemase-producing Enterobacteriaceae; ceftazidime-avibactam aztreonam

Outcome Measures

Primary Outcomes (1)

• All-cause mortality

  death from any cause

  within 30 days from the initiation of treatment (follow-up period)

Secondary Outcomes (6)

• Describe the resistance profile of the isolated microorganisms

  30-day follow-up period

• Compare clinical failure

  30-day follow-up period

• Compare the number of days to normalization of the leukocyte count in the laboratory

  30-day follow-up period

• Compare the proportion of adverse events

  30-day follow-up period

• compare the occurrence of Clostridium difficile infection

  30-day follow-up period

Study Arms (2)

CAZAVI + ATM

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.

Other Active Antibiotics treatment group

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.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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).

You may qualify if:

• Patients aged 18 years or older
• Confirmed bacteremia by MBL-type Carbapenemase-Producing Enterobacteriaceae (CPE)
• Initiation of effective antibiotic therapy within 24 hours of identification of MBL-type CPE and within 96 hours of blood sample.

You may not qualify if:

• Bacteremia due to the following complicated infections:
• Endocarditis or other endovascular infection without extractable focus.
• Necrotizing fasciitis
• Osteomyelitis or septic arthritis
• Confirmed prostatitis
• Non-drainable abscess or other unresolved infection requiring surgical intervention (e.g., cholecystitis)
• Central nervous system infections
• Empyema
• Successive episodes of bacteremia by the same pathogen (with the same resistance profile) within the previous 60 days.
• Polymicrobial bacteremias, not classified as contaminants.
• Patients with documented allergy to beta-lactams.

Sponsors & Collaborators

• Hospital Italiano de Buenos Aires: lead

Study Sites (16)

Hospital Municipal de Agudos Dr. Leónidas Lucero

Bahía Blanca, Buenos Aires, 8000, Argentina

Location

Hospital Interzonal General de Agudos ''Profesor Dr. Luis Güemes''

Haedo, Buenos Aires, 1706, Argentina

Location

Hospital de Alta Complejidad del Bicentenario Esteban Echeverria

Monte Grande, Buenos Aires, 1842, Argentina

Location

Hospital Universitario Austral

Pilar, Buenos Aires, 1629, Argentina

Location

Hospital Municipal Central de San Isidro "Dr. Melchor Ángel Posse"

San Isidro, Buenos Aires, 1641, Argentina

Location

Hospital Presidente Perón

Sarandí, Buenos Aires, 1872, Argentina

Location

Sanatorio Franchin

Buenos Aires, Buenos Aires F.D., 1039, Argentina

Location

Hospital Alemán

Buenos Aires, Buenos Aires F.D., 1118, Argentina

Location

Hospital de Infecciosas Francisco Javier Muñiz

Buenos Aires, Buenos Aires F.D., 1282, Argentina

Location

Hospital Italiano de Buenos Aires

Buenos Aires, Buenos Aires F.D., 1425, Argentina

Location

Hospital Médico Policial Churruca Visca

Buenos Aires, Buenos Aires F.D., 1437, Argentina

Location

Hospital Privado Universitario de Córdoba

Córdoba, Córdoba Province, 5016, Argentina

Location

Hospital Interdistrital Evita

Formosa, Formosa Province, 3600, Argentina

Location

Hospital Italiano Rosario

Rosario, Santa Fe Province, 2001, Argentina

Location

Hospital José Bernardo Iturraspe

Santa Fe, Santa Fe Province, 3000, Argentina

Location

Hospital José María Cullen

Santa Fe, Santa Fe Province, 3000, Argentina

Location

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Related Links

• Global antimicrobial resistance and use surveillance system (GLASS) report: 2022. World Health Organization; 9 Dec 2022 \[cited 3 Oct 2023\].
• Surveillance of antimicrobial resistance in Europe 2017. In: European Centre for Disease Prevention and Control

MeSH Terms

Conditions

Bacteremia

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Ivan Huespe, MD, MPh

  Hospital Italiano de Buenos Aires

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: May 14, 2024
• First Posted: May 17, 2024
• Study Start: June 1, 2024
• Primary Completion: November 19, 2024
• Study Completion: November 19, 2024
• Last Updated: November 21, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

AR (16)