Antimicrobial Therapy for Difficult-to-treat Pseudomonas Aeruginosa
- Conditions
- Pseudomonas InfectionsPseudomonas AeruginosaPrognosisDrug Resistance, Multiple, BacterialAntibacterial AgentsBeta-lactam Antibiotics
- Registration Number
- NCT06738771
- Lead Sponsor
- Centre Hospitalier Régional d'Orléans
- Brief Summary
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.
- 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).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 600
- All patients aged 18 or over and requiring intravenous definite antimicrobial therapy for a DTR P. aeruginosa infection
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Clinical cure rate 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).
Clinical cure 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).
- Secondary Outcome Measures
Name Time Method Microbiological eradication 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
Resistance emergence 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
Non-ecological adverse events 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
Acquisition of multidrug-resistant bacteria other than DTR P. aeruginosa 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
Clostridioides difficile infection Up to hospital discharge, an average of 1 month Documented C. difficile infection
In-hospital death Up to hospital discharge, an average of 1 month All-cause death
Death at Day 28 Day 28 All-cause death
Trial Locations
- Locations (48)
CHU Amiens
🇫🇷Amiens, France
CH Argenteuil
🇫🇷Argenteuil, France
CH Bayonne
🇫🇷Bayonne, France
CHU de BESANCON
🇫🇷Besançon, France
CHU Avicenne
🇫🇷Bobigny, France
CH Bourgoin-Jallieu
🇫🇷Bourgoin-Jallieu, France
CH Bethune
🇫🇷Béthune, France
CH Métropole Savoie
🇫🇷Chambéry, France
Ch de Chartres
🇫🇷Chartres, France
CHU Clermont Ferrand
🇫🇷Clermont-Ferrand, France
CHI Créteil
🇫🇷Créteil, France
CHU Henri Mondor
🇫🇷Créteil, France
CHI Elbeuf Louviers
🇫🇷Elbeuf, France
Hopital Raymond Poincaré
🇫🇷Garches, France
CHU Grenoble
🇫🇷Grenoble, France
CH Haguenau
🇫🇷Haguenau, France
CHD Vendée
🇫🇷La Roche-sur-Yon, France
Hopital Bicetre
🇫🇷Le Kremlin-Bicêtre, France
CHU Limoges
🇫🇷Limoges, France
CHU Lyon Sud
🇫🇷Lyon, France
CHU Lyon
🇫🇷Lyon, France
CHY Lyon
🇫🇷Lyon, France
Hopital Saint-Joseph Saint Luc
🇫🇷Lyon, France
CHU Montpellier
🇫🇷Montpellier, France
CHRU Nancy
🇫🇷Nancy, France
Chu de Nantes
🇫🇷Nantes, France
CHU de Nice
🇫🇷Nice, France
Centre Hospitalier Universitaire d'Orléans
🇫🇷Orléans, France
Hopital Bichat
🇫🇷Paris, France
Hopital Cochin
🇫🇷Paris, France
Hopital LARIBOISIERE
🇫🇷Paris, France
Hopital Pitie Salpetriere
🇫🇷Paris, France
Hopital Saint-Antoine
🇫🇷Paris, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
Hôpital Saint-Louis
🇫🇷Paris, France
CH PAU
🇫🇷Pau, France
CH Perpignan
🇫🇷Perpignan, France
Centre Hospitalier de Périgueux
🇫🇷Périgueux, France
CHU Reims
🇫🇷Reims, France
CH Saint-Lô
🇫🇷Saint-Lô, France
CHRU Strasbourg Haute Pierre
🇫🇷Strasbourg, France
CHU Strasbourg
🇫🇷Strasbourg, France
Hopital Foch
🇫🇷Suresnes, France
CH Tourcoing
🇫🇷Tourcoing, France
CH Vannes
🇫🇷Vannes, France
Hôpital Nord-Ouest de Villefranche sur Saone
🇫🇷Villefranche-sur-Saône, France
CH Sud Essone
🇫🇷Étampes, France
CHU La Réunion
🇷🇪Saint-Denis, Réunion