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

Recruiting

• Conditions: Antimicrobial Resistance (AMR); Gram Negative Infections

• Registration Number: NCT06717594
• Lead Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

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).

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 Timeline

• Study Start: 2023-12-01
• Status Verified: 2024-12
• Study First Submitted: 2024-12-01
• Study First Submitted QC: 2024-12-01
• Last Update Submitted: 2024-12-01
• Study First Posted: 2024-12-05
• Last Update Posted: 2024-12-05
• Primary Completion: 2025-01-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
PK/PD efficacy targets for study drugs	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

Secondary Outcome Measures

Name	Time	Method
Microbiological eradication	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
All-cause mortality	From enrollment to the end of the follow-up at three months	All-cause mortality at day 30 and at day 90
Difference in SOFA score	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
Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT)	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
Relapse and/or reinfection	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

Trial Locations

Locations (2)

IRCCS Azienda Ospedaliero-Universitaria di Bologna; 🇮🇹 Bologna, Italy

Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen Macarena/CSIC/Universidad de Sevilla; 🇪🇸 Seville, Spain