Antimicrobial Therapy for Difficult-to-treat Pseudomonas Aeruginosa (ADDICT)
April 29, 2026 updated by: Centre Hospitalier Régional d'Orléans
Antimicrobial Therapy for Infections Due to Pseudomonas Aeruginosa With Difficult-to-treat Resistance: a Real-world, Prospective, Multicenter Cohort Study
The primary objective of the ADDICT study is to assess and compare the clinical efficacy of available options for antimicrobial therapy (new beta-lactam/beta-lactamase inhibitor combination, cefiderocol or older agents such as aminoglycosides and colistin) in unselected patients with infection due to difficult-to-treat P. aeruginosa.
Study Overview
Status
Recruiting
Detailed Description
Infections due to Pseudomonas aeruginosa isolates with acquired resistances to all first-line antipseudomonal beta-lactams and fluoroquinolones (difficult-to-treat isolates - DTR), pose serious therapeutical challenges, especially in critically ill and/or immunocompromised patients. Certain new beta-lactam/beta-lactamase inhibitor combinations (BL/BLI (beta lactamine/ beta lactamase inhibitor) - i.e., ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, others) and cefiderocol have shown promising results for the treatment of infections due to DTR P. aeruginosa. However, multicenter data on their real-life utilization in this indication are still scarce.
The ADDICT study is a prospective, multicenter cohort study including unselected patients with DTR P. aeruginosa infection requiring definite intravenous antimicrobial therapy. The primary objective of the study is to investigate the clinical efficacy of available options (new BL/BLI, cefiderocol or older agents such as aminoglycosides and colistin) in this population. Secondary objectives are to compare the clinical and microbiological efficacy of available options in infections due to DTR P. aeruginosa with in vitro susceptibility to more than one last-resort drug, to compare the incidence of non-ecological adverse events observed with these drugs, to assess the incidence of resistance emergence under therapy and to elucidate the molecular mechanisms of resistance emergence, to assess the benefits and risks of combination therapy in this indication, to compare the acquisition rates of multidrug-resistant bacteria other than DTR P. aeruginosa, and Clostridioides difficile infection, to compare Day-28 and in-hospital all-cause mortality rates.
Patients will be recruited in 60 hospital centers contributing to four French networks of research in infectious diseases and critical care (CRICS-TRIGGERSEP, ReaRezo, OutcomeRéa, RENARCI - PROMISE metanetwork). Clinical variables will be collected through an electronic case-report form. DTR P. aeruginosa isolates will be sent to the National Reference Center of Antimicrobial Resistance in P. aeruginosa for centralized analyses (extended antimicrobial susceptibility testing, MLST, whole-genome sequencing of successive isolates if resistance emergence under therapy).
Study Type
Observational
Enrollment (Estimated)
600
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: Francois BARBIER, Professor
- Phone Number: +33238229939
- Email: francois.barbier@chu-orleans.fr
Study Locations
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Amiens, France
- Not yet recruiting
- CHU Amiens
-
Contact:
- Stéphanie MALAQUIN, Dr
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Principal Investigator:
- Stéphanie MALAQUIN, Dr
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Argenteuil, France
- Not yet recruiting
- CH Argenteuil
-
Contact:
- Olivier PAJOT, Dr
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Principal Investigator:
- Olivier PAJOT, Dr
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Bayonne, France
- Not yet recruiting
- CH Bayonne
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Contact:
- Marc-Olivier VAREIL, Dr
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Principal Investigator:
- Marc-Olivier VAREIL, Dr
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Besançon, France
- Not yet recruiting
- CHU de Besancon
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Contact:
- Catherine CHIROUZE, Pr
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Principal Investigator:
- Catherine CHIROUZE, Pr
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Bobigny, France
- Not yet recruiting
- CHU Avicenne
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Contact:
- Khalil CHAIBI, Dr
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Principal Investigator:
- Khalil CHAIBI, Dr
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Bourgoin, France
- Not yet recruiting
- CH Bourgoin-Jallieu
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Contact:
- Abdelhamid FATAH, Dr
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Principal Investigator:
- Abdelhamid FATAH, Dr
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Béthune, France
- Not yet recruiting
- CH Bethune
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Contact:
- Sophie NGUYEN, Dr
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Principal Investigator:
- Sophie NGUYEN, Dr
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Chambéry, France
- Not yet recruiting
- CH Métropole Savoie
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Contact:
- Emmanuel FORESTIER, Dr
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Principal Investigator:
- Emmanuel FORESTIER, Dr
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Chartres, France
- Not yet recruiting
- Ch de Chartres
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Contact:
- Juliette AUDIBERT, Dr
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Principal Investigator:
- Juliette AUDIBERT, Dr
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Clermont-Ferrand, France
- Not yet recruiting
- Chu Clermont Ferrand
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Contact:
- Claire DUPUIS, Pr
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Principal Investigator:
- Claire DUPUIS, Pr
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Créteil, France
- Not yet recruiting
- Chu Henri Mondor
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Contact:
- Keyvan RAZAZI, Pr
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Principal Investigator:
- Keyvan RAZAZI, Pr
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Créteil, France
- Not yet recruiting
- Chi Creteil
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Contact:
- Rusel LEON, Dr
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Principal Investigator:
- Rusel LEON, Dr
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Elbeuf, France
- Not yet recruiting
- CHI Elbeuf Louviers
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Contact:
- Christian CAILLARD, Dr
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Principal Investigator:
- Christian CAILLARD, Dr
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Garches, France
- Not yet recruiting
- Hopital Raymond Poincare
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Contact:
- Aurélien DINH, Pr
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Principal Investigator:
- Aurélien DINH, Pr
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Grenoble, France
- Not yet recruiting
- CHU Grenoble
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Contact:
- Hugo PIROLLET, Dr
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Principal Investigator:
- Hugo PIROLLET, Dr
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Haguenau, France
- Not yet recruiting
- CH Haguenau
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Contact:
- Asael BERGER, PhD
- Email: Asael.BERGER@ch-haguenau.fr
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Principal Investigator:
- Asael BERGER, PhD
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La Roche-sur-Yon, France
- Recruiting
- CHD Vendee
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Contact:
- Thomas GUIMARD, Dr
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Principal Investigator:
- Thomas GUIMARD, Dr
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Le Kremlin-Bicêtre, France
- Not yet recruiting
- Hôpital Bicêtre
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Contact:
- Leila ESCAUT, Dr
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Principal Investigator:
- Leila ESCAUT, Dr
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Limoges, France
- Not yet recruiting
- CHU Limoges
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Contact:
- Julien VAIDIE, Dr
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Principal Investigator:
- Julien VAIDIE, Dr
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Lyon, France
- Not yet recruiting
- CHU Lyon
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Principal Investigator:
- Laurent ARGAUD, Pr
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Contact:
- Laurent ARGAUD, Pr
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Lyon, France
- Not yet recruiting
- CHU Lyon Sud
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Principal Investigator:
- Arnaud FRIGGERI, Pr
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Contact:
- Arnaud FRIGGERI, Pr
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Lyon, France
- Not yet recruiting
- CHY Lyon
-
Principal Investigator:
- Jean-Christophe RICHARD, Pr
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Contact:
- Jean-Christophe RICHARD, Pr
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Lyon, France
- Not yet recruiting
- Hopital Saint-Joseph Saint Luc
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Contact:
- Emmanuel VIVIER, Dr
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Principal Investigator:
- Emmanuel Vivier, Dr
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Montpellier, France
- Not yet recruiting
- CHU Montpellier
-
Contact:
- Vincent LE MOING, Pr
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Principal Investigator:
- Vincent LE MOING, Pr
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Nancy, France
- Recruiting
- CHRU Nancy
-
Contact:
- Benjamin LEFEVRE, Dr
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Principal Investigator:
- Benjamin LEFEVRE, Dr
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Nantes, France
- Not yet recruiting
- CHU de Nantes
-
Contact:
- David BOUTOILLE, Pr
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Principal Investigator:
- DAvid BOUTOILLE, Pr
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Nice, France
- Not yet recruiting
- CHU de Nice
-
Contact:
- Alexandre ROBERT, Dr
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Principal Investigator:
- Alexandre ROBERT, Dr
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Orléans, France
- Recruiting
- Centre Hospitalier Universitaire d'Orléans
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Contact:
- Francois BARBIER, Professor
- Phone Number: +33238229939
- Email: francois.barbier@chu-orleans.fr
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Principal Investigator:
- François BARBIER, Pr
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Paris, France
- Not yet recruiting
- Hopital Pitie Salpetriere
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Contact:
- Charles-Edouard LUYT, Pr
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Principal Investigator:
- Charles-Edouard LUYT, Pr
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Paris, France
- Not yet recruiting
- Hopital Europeen Georges Pompidou
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Contact:
- Damien BLEZ, Dr
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Principal Investigator:
- Damien BLEZ, Dr
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Paris, France
- Not yet recruiting
- Hopital Saint-Louis
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Contact:
- Matthieu LAFAURIE, Dr
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Principal Investigator:
- Matthieu LAFAURIE, Dr
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Paris, France
- Not yet recruiting
- Hopital Lariboisiere
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Contact:
- Anne-Lise MUNIER, Dr
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Principal Investigator:
- Anne-Lise MUNIER, Dr
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Paris, France
- Recruiting
- Hôpital Bichat
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Contact:
- Jean-François TIMSIT, Pr
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Principal Investigator:
- Jean-François TIMSIT, Pr
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Paris, France
- Not yet recruiting
- Hopital Cochin
-
Contact:
- Antoine BOIS, Dr
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Principal Investigator:
- Antoine BOIS, Dr
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Paris, France
- Not yet recruiting
- Hôpital Saint-Antoine
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Contact:
- Laure SURGERS, Dr
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Principal Investigator:
- Laure SURGERS, Dr
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Pau, France
- Not yet recruiting
- CH PAU
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Contact:
- Mélanie LEHOUX, Dr
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Principal Investigator:
- Mélanie LEHOUX, Dr
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Perpignan, France
- Not yet recruiting
- CH Perpignan
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Contact:
- Hugues AUMAITRE, Dr
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Principal Investigator:
- Hugues AUMAITRE, Dr
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Périgueux, France
- Not yet recruiting
- Centre Hospitalier de Perigueux
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Contact:
- Mélanie SAINT-LEGER, Dr
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Principal Investigator:
- Mélanie SAINT-LEGER, Dr
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Reims, France
- Not yet recruiting
- Chu Reims
-
Contact:
- Marin MOUTEL, Dr
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Principal Investigator:
- Marin MOUTEL, Dr
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Saint-Lô, France
- Not yet recruiting
- CH Saint-Lô
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Contact:
- Alexandre ALLAIRE, Dr
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Principal Investigator:
- Alexandre ALLAIRE, Dr
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Strasbourg, France
- Not yet recruiting
- CHU Strasbourg
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Contact:
- Ferhat MEZIANI, Dr
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Principal Investigator:
- Ferhat MEZIANI, Dr
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Strasbourg, France
- Not yet recruiting
- CHRU Strasbourg Haute Pierre
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Contact:
- Vincent CASTELAIN, Professor
- Email: Vincent.CASTELAIN@chru-strasbourg.fr
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Principal Investigator:
- Vincent CASTELAIN, Pr
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Suresnes, France
- Not yet recruiting
- Hopital Foch
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Contact:
- Marie-Alice COLOMBIER, Dr
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Principal Investigator:
- Marie-Alice COLOMBIER, Dr
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Tourcoing, France
- Not yet recruiting
- Ch Tourcoing
-
Contact:
- Serge ALFANDARI, Dr
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Principal Investigator:
- Serge ALFANDARI, Dr
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Vannes, France
- Not yet recruiting
- CH Vannes
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Contact:
- Florian REIZINE, Dr
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Principal Investigator:
- Florian REIZINE, Dr
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Villefranche-sur-Saône, France
- Not yet recruiting
- Hôpital Nord-Ouest de Villefranche sur Saone
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Contact:
- Gary DAVID, Dr
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Principal Investigator:
- Gary DAVID, Dr
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Étampes, France
- Not yet recruiting
- CH Sud Essone
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Contact:
- Siami SHIDASP, Dr
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Principal Investigator:
- Siami SHIDASP, Dr
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Saint-Denis, Reunion
- Not yet recruiting
- CHU La Réunion
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Contact:
- Kévin DIALLO, Dr
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Principal Investigator:
- Kévin DIALLO, Dr
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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
No
Sampling Method
Non-Probability Sample
Study Population
Prospective multicenter cohort
Description
Inclusion Criteria:
- All patients aged 18 or over and requiring intravenous definite antimicrobial therapy for a DTR P. aeruginosa infection
Exclusion Criteria:
- Cystic fibrosis
- P. aeruginosa DTR colonization or P. aeruginosa DTR infection not requiring definitive intravenous antibiotic therapy
- Protected person (under guardianship or curatorship)
- Persons under court protection
- Persons deprived of liberty
- Opposition expressed for participation in the study
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
Cohorts and Interventions
Group / Cohort |
|---|
|
1
patients with invasive P. aeruginosa DTR infection requiring definitive intravenous antibiotic therapy
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Clinical cure rate
Time Frame: Test of cure visit
|
Clinical responses will be assessed by local investigators.
Clinical cure will be defined as a composite endpoint of survival with no relapse occurring since the end of definite therapy and the complete resolution of all initial clinical signs of infection at the ToC visit (all-cause deaths at the ToC visit will be considered as clinical failures).
|
Test of cure visit
|
|
Clinical cure
Time Frame: Day 7±2 after the completion of definite therapy
|
Clinical responses will be assessed by local investigators.
Clinical cure will be defined as a composite endpoint of survival with no relapse occurring since the end of definite therapy and the complete resolution of all initial clinical signs of infection at the ToC visit (all-cause deaths at the ToC visit will be considered as clinical failures).
|
Day 7±2 after the completion of definite therapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Microbiological eradication
Time Frame: Day 7
|
Negativation of cultures for DTR P. aeruginosa in participants with at least one collected follow-up bacteriological sample (when clinically indicated) before the ToC visit
|
Day 7
|
|
Resistance emergence
Time Frame: Up to hospital discharge, an average of 1 month
|
Any culture growing a DTR P. aeruginosa isolate with resistance to at least one new antimicrobial agent (compared to the first isolate) between the second day of definite therapy and hospital discharge
|
Up to hospital discharge, an average of 1 month
|
|
Non-ecological adverse events
Time Frame: At test-of-cure visit, 7±2 days after the completion of definite therapy
|
Any toxicity or allergic reaction attributed to the antimicrobial agent by the local investigator
|
At test-of-cure visit, 7±2 days after the completion of definite therapy
|
|
Non-ecological adverse events
Time Frame: From the first day of definite therapy to the ToC visit
|
Any toxicity or allergic reaction attributed to the antimicrobial agent by the local investigator
|
From the first day of definite therapy to the ToC visit
|
|
Acquisition of multidrug-resistant bacteria other than DTR P. aeruginosa
Time Frame: Up to hospital discharge, an average of 1 month
|
Culture of any clinical or surveillance sample growing a multidrug-resistant bacteria other than P. aeruginosa
|
Up to hospital discharge, an average of 1 month
|
|
Clostridioides difficile infection
Time Frame: Up to hospital discharge, an average of 1 month
|
Documented C. difficile infection
|
Up to hospital discharge, an average of 1 month
|
|
In-hospital death
Time Frame: Up to hospital discharge, an average of 1 month
|
All-cause death
|
Up to hospital discharge, an average of 1 month
|
|
Death at Day 28
Time Frame: Day 28
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All-cause death
|
Day 28
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Francois BARBIER, Professor, Centre Hospitalier Universitaire d'Orléans
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Tamma PD, Aitken SL, Bonomo RA, Mathers AJ, van Duin D, Clancy CJ. Infectious Diseases Society of America 2022 Guidance on the Treatment of Extended-Spectrum beta-lactamase Producing Enterobacterales (ESBL-E), Carbapenem-Resistant Enterobacterales (CRE), and Pseudomonas aeruginosa with Difficult-to-Treat Resistance (DTR-P. aeruginosa). Clin Infect Dis. 2022 Aug 25;75(2):187-212. doi: 10.1093/cid/ciac268.
- Hu F, Guo Y, Yang Y, Zheng Y, Wu S, Jiang X, Zhu D, Wang F; China Antimicrobial Surveillance Network (CHINET) Study Group. Resistance reported from China antimicrobial surveillance network (CHINET) in 2018. Eur J Clin Microbiol Infect Dis. 2019 Dec;38(12):2275-2281. doi: 10.1007/s10096-019-03673-1. Epub 2019 Sep 2.
- Karlowsky JA, Lob SH, Kazmierczak KM, Young K, Motyl MR, Sahm DF. In-vitro activity of imipenem/relebactam and key beta-lactam agents against Gram-negative bacilli isolated from lower respiratory tract infection samples of intensive care unit patients - SMART Surveillance United States 2015-2017. Int J Antimicrob Agents. 2020 Jan;55(1):105841. doi: 10.1016/j.ijantimicag.2019.10.022. Epub 2019 Nov 6.
- Rosenthal VD, Bat-Erdene I, Gupta D, Belkebir S, Rajhans P, Zand F, Myatra SN, Afeef M, Tanzi VL, Muralidharan S, Gurskis V, Al-Abdely HM, El-Kholy A, AlKhawaja SAA, Sen S, Mehta Y, Rai V, Hung NV, Sayed AF, Guerrero-Toapanta FM, Elahi N, Morfin-Otero MDR, Somabutr S, De-Carvalho BM, Magdarao MS, Velinova VA, Quesada-Mora AM, Anguseva T, Ikram A, Aguilar-de-Moros D, Duszynska W, Mejia N, Horhat FG, Belskiy V, Mioljevic V, Di-Silvestre G, Furova K, Gamar-Elanbya MO, Gupta U, Abidi K, Raka L, Guo X, Luque-Torres MT, Jayatilleke K, Ben-Jaballah N, Gikas A, Sandoval-Castillo HR, Trotter A, Valderrama-Beltran SL, Leblebicioglu H; International Nosocomial Infection Control Consortium. International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2012-2017: Device-associated module. Am J Infect Control. 2020 Apr;48(4):423-432. doi: 10.1016/j.ajic.2019.08.023. Epub 2019 Oct 29.
- Sader HS, Streit JM, Carvalhaes CG, Huband MD, Shortridge D, Mendes RE, Castanheira M. Frequency of occurrence and antimicrobial susceptibility of bacteria isolated from respiratory samples of patients hospitalized with pneumonia in Western Europe, Eastern Europe and the USA: results from the SENTRY Antimicrobial Surveillance Program (2016-19). JAC Antimicrob Resist. 2021 Sep 2;3(3):dlab117. doi: 10.1093/jacamr/dlab117. eCollection 2021 Sep.
- Hu F, Yuan L, Yang Y, Xu Y, Huang Y, Hu Y, Ai X, Zhuo C, Su D, Shan B, Du Y, Yu Y, Lin J, Sun Z, Chen Z, Xu Y, Zhang X, Wang C, He L, Ni Y, Zhang Y, Lin D, Zhu D, Zhang Y. A multicenter investigation of 2,773 cases of bloodstream infections based on China antimicrobial surveillance network (CHINET). Front Cell Infect Microbiol. 2022 Dec 15;12:1075185. doi: 10.3389/fcimb.2022.1075185. eCollection 2022.
- Tabah A, Buetti N, Staiquly Q, Ruckly S, Akova M, Aslan AT, Leone M, Conway Morris A, Bassetti M, Arvaniti K, Lipman J, Ferrer R, Qiu H, Paiva JA, Povoa P, De Bus L, De Waele J, Zand F, Gurjar M, Alsisi A, Abidi K, Bracht H, Hayashi Y, Jeon K, Elhadi M, Barbier F, Timsit JF; EUROBACT-2 Study Group, ESICM, ESCMID ESGCIP and the OUTCOMEREA Network. Epidemiology and outcomes of hospital-acquired bloodstream infections in intensive care unit patients: the EUROBACT-2 international cohort study. Intensive Care Med. 2023 Feb;49(2):178-190. doi: 10.1007/s00134-022-06944-2. Epub 2023 Feb 10.
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)
March 11, 2025
Primary Completion (Estimated)
January 1, 2027
Study Completion (Estimated)
January 1, 2027
Study Registration Dates
First Submitted
November 26, 2024
First Submitted That Met QC Criteria
December 13, 2024
First Posted (Actual)
December 18, 2024
Study Record Updates
Last Update Posted (Actual)
April 30, 2026
Last Update Submitted That Met QC Criteria
April 29, 2026
Last Verified
April 1, 2026
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2023-HORS RIPH-11
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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