Clinical trial NCT06717594: PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to CRE
Official title: PK/PD Relationship of CAZ/AVI and FOS in the Treatment of Patients With Infections Due to Carbapenem-resistant Enterobacterales (CRE)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Gram Negative Infections
Antimicrobial Resistance (AMR)
Keywords: Gram negative infection
Ceftazidime/Avibactam
Fosfomycin
Pharmacokinetics/Pharmacodynamics targets
Carbapenem-resistant Enterobacterales (CRE)
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2024-12-05
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

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.

Eligibility criteria: 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

Primary outcomes:
measure: PK/PD efficacy targets for study drugs
timeFrame: From enrollment (treatment onset) to 48 and 72 hours after starting treatment
Secondary outcomes:
measure: Difference in SOFA score
timeFrame: From day 0 (day of index positive culture) and day 7
measure: Trend of C-Reactive Protein (CRP) and Procalcitonin (PCT)
timeFrame: From day 0 (day of index positive culture) and day 7
measure: Microbiological eradication
timeFrame: From day 0 (day of index positive culture) and day 7
measure: Relapse and/or reinfection
timeFrame: From enrollment to the end of the follow-up at three months
measure: All-cause mortality
timeFrame: From enrollment to the end of the follow-up at three months
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
city: Seville
country: Spain
facility: Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen Macarena/CSIC/Universidad de Sevilla
Study officials:
affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: Maddalena Giannella, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: