Use of Cefiderocol in the Management of Gram-Negative Infections

Study Overview
=================
Brief Summary
-----------------
The aim of this study is to describe the use of cefiderocol in the management of Gram-negative infections (GNIs) in participants treated through the Early Access Program (EAP) in Spain.

Detailed Description
-----------------
This is a multicenter, retrospective, chart review of existing medical records in participants who received cefiderocol for a GNI as part of the Shionogi EAP. Access to cefiderocol was granted as Medication not approved in Spain subject to RD 1015/2009, which dictates that each case is approved on an individual basis by the Spanish Agency of Medicines. This study will be conducted at Spanish sites where cefiderocol was supplied via the EAP, beginning in 2018.

Official Title
-----------------
Retrospective Analysis of Real-World Use of Cefiderocol in the Management of Gram-Negative Infections as Part of the Early Access Program (PERSEUS Study)

Conditions
-----------------
Gram-Negative Infection

Intervention / Treatment
-----------------
* Drug: Cefiderocol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have received first course of cefiderocol. Have received treatment for at least 72 hours (complete) with cefiderocol as a part of clinical compassionate management, requested in the EAP. Exclusion Criteria: Enrolled in any clinical trial of an investigational product. Documented Acinetobacter spp infection. Incomplete medical records for the following essential data elements: Cefiderocol usage (dose, duration, frequency) Data to be able to determine clinical success (primary objective) Co-infection with a GNB resistant to cefiderocol in 28 days of the initial dose of cefiderocol.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cefiderocol Treated<br>Participants who have been treated with at least 72 hours of cefiderocol through the EAP in Spain. | Drug: Cefiderocol<br>* Cefiderocol is a novel siderophore cephalosporin developed for the treatment of infections caused by Gram-negative bacteria (GNB), including those resistant to carbapenems.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate Of Clinical Success | The rate of clinical success will be reported as the percent clinical success of participants treated with cefiderocol for participants who receive at least 72 hours of cefiderocol through the EAP for the treatment of Gram-negative, carbapenem-resistant infections (except for Acinetobacter spp). | From Day 1 (cefiderocol initiation) through Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Experiencing Resolution of Infection or Clinical Cure After Treatment With Cefiderocol |  | Day 1 (cefiderocol initiation), every 7 days up to Day 28 | 
| In-hospital Length of Stay | Length of stay in hospital (days) for participants with infections treated by cefiderocol will be reported. | Day 1 (cefiderocol initiation) up to Day 28, death, or discharge (whichever occurs first) | 
| Length of Stay in Intensive Care Unit (ICU) | Length of stay in ICU (days) for participants with infections treated by cefiderocol will be reported. | Day 1 (cefiderocol initiation) up to Day 28, death, or discharge (whichever occurs first) | 
| Length of Invasive Ventilation | Length of invasive ventilation (days) for participants with infections treated by cefiderocol will be reported. | Day 1 (cefiderocol initiation) up to Day 28, death, or discharge (whichever occurs first) | 
| All-cause In-hospital Mortality | All-cause in-hospital mortality will be reported after cefiderocol initiation. | Day 14, Day 28 | 
| Cause of Death | The relation of death to the reference infection, as reported in the medical notes, will be reported. | Day 1 (cefiderocol initiation) through Day 28 | 
| Rate of Microbiological Eradication | The rate of eradication of carbapenem-resistant GNIs will be reported as the percent microbiological eradication among participants with blood stream infections (BSIs) and complicated urinary tract infections (cUTIs)/UTIs from 24 hours of cefiderocol initiation until Day 28. BSI microbiological eradication will be defined as the absence of a positive follow-up blood culture, in which the same organism as the initial blood culture was obtained. Any positive blood cultures drawn within 24 hours of the initial positive culture will be considered as the same episode. cUTI/UTI microbiological eradication will be defined as an absence of a positive follow-up culture of the same organism as the initial infection obtained. | Day 1 (24 hours post cefiderocol initiation) through Day 28 | 
| Severity of Illness | The severity of illness at the time of cefiderocol administration at baseline will be described by a Sequential Organ Failure Assessment (SOFA) Score, quickSOFA (qSOFA) score, level of organ support, and presence of septic shock. The SOFA score for participants in ICU or qSOFA score for participants outside ICU will be reported for days -3, 0, and 7 in relation to the date of cefiderocol initiation. | Day 1 (cefiderocol initiation) through Day 28 | 
| Number of Participants With Adverse Drug Reactions (ADRs) | The number of participants with serious and non-serious adverse events with explicit attribution to cefiderocol (ADR) will be reported. | Up to 28 days post-treatment completion with cefiderocol, death, or discharge (whichever occurs first) | 
| Number of Participants Experiencing Resolution of Infection or Clinical Cure After Prolonged Treatment With Cefiderocol |  | Day 1 (cefiderocol initiation), every 10 days up to Day 60 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cefiderocol, Early Access Program, Spain