PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to CRE

NCT06717594 | Recruiting

• 2 other identifiers: CAVIFOSJPIAMR-ACTION
• Study Type: observational
• Target: 60
• Locations: 2 countries
• Sites: 2

Brief Summary

A multicenter international prospective observational pharmacological study in adult patients (≥18 years) treated with ceftazidime/avibactam (CAZ/AVI) alone or with CAZ/AVI plus fosfomycin (FOS) for infection due to carbapenem-resistant Enterobacterales (CRE) (KPC and/or OXA-48).

Conditions

Gram Negative Infections; Antimicrobial Resistance (AMR)

Keywords

Gram negative infection; Ceftazidime/Avibactam; Fosfomycin; Pharmacokinetics/Pharmacodynamics targets; Carbapenem-resistant Enterobacterales (CRE)

Outcome Measures

Primary Outcomes (1)

• PK/PD efficacy targets for study drugs

  The primary endpoint will be the attainment of the pre-defined PK/PD target of efficacy at 48 and 72 hours after starting treatment for Carbapenem-resistant Enterobacterales (CRE) infection

  From enrollment (treatment onset) to 48 and 72 hours after starting treatment

Secondary Outcomes (5)

• Difference in SOFA score

  From day 0 (day of index positive culture) and day 7

• Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT)

  From day 0 (day of index positive culture) and day 7

• Microbiological eradication

  From day 0 (day of index positive culture) and day 7

• Relapse and/or reinfection

  From enrollment to the end of the follow-up at three months

• All-cause mortality

  From enrollment to the end of the follow-up at three months

Study Arms (1)

Patients with Carbapenem-resistant Enterobacterales (CRE) infection treated with CAZ/AVI ± FOS

Adult patients treated for ≥ 48 hours with CAZ/AVI or CAZ/AVI plus FOS for a microbiologically documented CRE infection

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

Adult patients with infection due to a difficult-to-treat Gram-negative bacteria, treated with CAZ/AVI alone or CAZ/AVI plus FOS, hospitalized during the study period in the participating centers, will be screened for inclusion

You may qualify if:

• Signature of the informed consent
• Age ≥ 18 years
• Adult patients treated for ≥ 48 hours with CAZ/AVI or CAZ/AVI plus FOS for a microbiologically documented CRE infection

You may not qualify if:

• Polymicrobial/mixed infections with exception of cases with multiple Enterobacterales susceptible to study drugs

Sponsors & Collaborators

• IRCCS Azienda Ospedaliero-Universitaria di Bologna: lead

Study Sites (2)

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Bologna, Bologna, 40138, Italy

RECRUITING

Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen Macarena/CSIC/Universidad de Sevilla

Seville, Seville, 41013, Spain

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

* Serum samples for PK/PD analysis * Isolated bacterial strains

Study Officials

• Maddalena Giannella, MD PhD

  IRCCS Azienda Ospedaliero-Universitaria di Bologna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maddalena Giannella, MD PhD

CONTACT

+390512143199; maddalena.giannella@unibo.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2024
• First Posted: December 5, 2024
• Study Start: December 1, 2023
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: November 28, 2025

Record last verified: 2025-11

Locations

ES (1); IT (1)