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| ID | Type | Description | Link |
|---|---|---|---|
| JPIAMR-ACTION | Other Grant/Funding Number | Italian Ministry of Health |
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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Difference in SOFA score | 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) |
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Inclusion Criteria:
Exclusion Criteria:
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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
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Maddalena Giannella, MD PhD | Contact | +390512143199 | maddalena.giannella@unibo.it |
| Name | Affiliation | Role |
|---|---|---|
| Maddalena Giannella, MD PhD | IRCCS Azienda Ospedaliero-Universitaria di Bologna | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| IRCCS Azienda Ospedaliero-Universitaria di Bologna | Recruiting | Bologna | Bologna | 40138 | Italy |
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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 | 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 |
| Relapse and/or reinfection | 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 | All-cause mortality at day 30 and at day 90 | From enrollment to the end of the follow-up at three months |
| Instituto de Biomedicina de Sevilla (IBiS), Hospital Virgen Macarena/CSIC/Universidad de Sevilla | Recruiting | Seville | Seville | 41013 | Spain |
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