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

June 11, 2026 updated by: IRCCS Azienda Ospedaliero-Universitaria di Bologna

PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to Carbapenem-resistant Enterobacterales (CRE)

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).

Study Overview

Status

Recruiting

Conditions

Detailed Description

Gram-negative infections, particularly those caused by carbapenem-resistant Enterobacterales (CRE), have a dramatic impact on patient survival. Despite the introduction of new drugs in the last years have improved the outcome of patients with CRE infections, mortality and relapse rates are still relevant, especially in patients with high-risk source as pneumonia, and those in which the attainment of optimal exposure could be reduced by underlying renal disease. The use of combination regimen in these scenarios has been proposed. However, a standardized approach is still missing. Since several in vitro studies have highlighted the synergistic effect of fosfomycin (FOS) with different antibiotic classes, including cephalosporins such drug could be an appealing option in combination therapy for the management of CRE infections.

In particular, the primary aim of the study is to assess the probability of achieving a pre-defined target of efficacy in patients treated with ceftazidime/avibactam (CAZ/AVI) and/or FOS according to different modes of drug administration in patients with CRE infections.

Secondary aim is to assess the association between plasma drug concentration of both CAZ/AVI and FOS and patient response.

Study Type

Observational

Enrollment (Estimated)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: Maddalena Giannella, MD PhD
Phone Number: +390512143199
Email: maddalena.giannella@unibo.it

Study Locations

Italy
- Bologna
  - Bologna, Bologna, Italy, 40138
    - Recruiting
    - IRCCS Azienda Ospedaliero-Universitaria di Bologna
    - Contact:
      
      Maddalena Giannella, MD PhD
      
      Phone Number: +390512143199
      
      Email: maddalena.giannella@unibo.it
Spain
- Seville
  - Seville, Seville, Spain, 41013
    - Recruiting
    - Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen Macarena/CSIC/Universidad de Sevilla
    - Contact:
      
      Fernando M Docobo Pérez, PhD
      
      Phone Number: +34 954118805
      
      Email: fdocobo1@us.es

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult
Older Adult

Accepts Healthy Volunteers

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

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK/PD efficacy targets for study drugs Time Frame: From enrollment (treatment onset) to 48 and 72 hours after starting treatment	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse and/or reinfection Time Frame: From enrollment to the end of the follow-up at three months	Relapse (new infection with the same pathogen emerging after treatment) and/or reinfection (new infection with a different pathogen emerging after treatment) rates at day 90	From enrollment to the end of the follow-up at three months
All-cause mortality Time Frame: From enrollment to the end of the follow-up at three months	All-cause mortality at day 30 and at day 90	From enrollment to the end of the follow-up at three months
Difference in SOFA score Time Frame: From day 0 (day of index positive culture) and day 7	Difference in SOFA score between day 0 (day of treatment onset) and day 7	From day 0 (day of index positive culture) and day 7
Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT) Time Frame: From day 0 (day of index positive culture) and day 7	Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT) from day 0 to day 7 after treatment onset	From day 0 (day of index positive culture) and day 7
Microbiological eradication Time Frame: From day 0 (day of index positive culture) and day 7	Microbiological eradication defined as bacteraemia clearance or negativization of index diagnostic sample within 7 days from treatment onset	From day 0 (day of index positive culture) and day 7

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IRCCS Azienda Ospedaliero-Universitaria di Bologna

Investigators

Principal Investigator: Maddalena Giannella, MD PhD, IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2023

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

December 1, 2024

First Submitted That Met QC Criteria