Clinical trial NCT06738771: Antimicrobial Therapy for Difficult-to-treat Pseudomonas Aeruginosa
Official title: Antimicrobial Therapy for Infections Due to Pseudomonas Aeruginosa With Difficult-to-treat Resistance: a Real-world, Prospective, Multicenter Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Pseudomonas Infections
Pseudomonas Aeruginosa
Prognosis
Drug Resistance, Multiple, Bacterial
Antibacterial Agents
Beta-lactam Antibiotics
Lead sponsor: Centre Hospitalier Régional d'Orléans
Sponsor class: OTHER
First posted: 2024-12-18
Enrollment: 600
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: Prospective multicenter cohort

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).

Eligibility criteria: 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

Primary outcomes:
measure: Clinical cure rate
timeFrame: Test of cure visit
measure: Clinical cure
timeFrame: Day 7±2 after the completion of definite therapy
Secondary outcomes:
measure: Microbiological eradication
timeFrame: Day 7
measure: Resistance emergence
timeFrame: Up to hospital discharge, an average of 1 month
measure: Non-ecological adverse events
timeFrame: At test-of-cure visit, 7±2 days after the completion of definite therapy
measure: Non-ecological adverse events
timeFrame: From the first day of definite therapy to the ToC visit
measure: Acquisition of multidrug-resistant bacteria other than DTR P. aeruginosa
timeFrame: Up to hospital discharge, an average of 1 month
measure: Clostridioides difficile infection
timeFrame: Up to hospital discharge, an average of 1 month
measure: In-hospital death
timeFrame: Up to hospital discharge, an average of 1 month
measure: Death at Day 28
timeFrame: Day 28
Other outcomes:
Locations:
city: Amiens
country: France
facility: CHU Amiens
city: Argenteuil
country: France
facility: CH Argenteuil
city: Bayonne
country: France
facility: CH Bayonne
city: Besançon
country: France
facility: CHU de BESANCON
city: Bobigny
country: France
facility: CHU Avicenne
city: Bourgoin-Jallieu
country: France
facility: CH Bourgoin-Jallieu
city: Béthune
country: France
facility: CH Bethune
city: Chambéry
country: France
facility: CH Métropole Savoie
city: Chartres
country: France
facility: Ch de Chartres
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand
city: Créteil
country: France
facility: CHI Créteil
city: Créteil
country: France
facility: CHU Henri Mondor
city: Elbeuf
country: France
facility: CHI Elbeuf Louviers
city: Garches
country: France
facility: Hopital Raymond Poincaré
city: Grenoble
country: France
facility: CHU Grenoble
city: Haguenau
country: France
facility: CH Haguenau
city: La Roche-sur-Yon
country: France
facility: CHD Vendée
city: Le Kremlin-Bicêtre
country: France
facility: Hopital Bicetre
city: Limoges
country: France
facility: CHU Limoges
city: Lyon
country: France
facility: CHU Lyon Sud
city: Lyon
country: France
facility: CHU Lyon
city: Lyon
country: France
facility: CHY Lyon
city: Lyon
country: France
facility: Hopital Saint-Joseph Saint Luc
city: Montpellier
country: France
facility: CHU Montpellier
city: Nancy
country: France
facility: CHRU Nancy
city: Nantes
country: France
facility: Chu de Nantes
city: Nice
country: France
facility: CHU de Nice
city: Orléans
country: France
facility: Centre Hospitalier Universitaire d'Orléans
city: Paris
country: France
facility: Hopital Bichat
city: Paris
country: France
facility: Hopital Cochin
city: Paris
country: France
facility: Hopital LARIBOISIERE
city: Paris
country: France
facility: Hopital Pitie Salpetriere
city: Paris
country: France
facility: Hopital Saint-Antoine
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Saint-Louis
city: Pau
country: France
facility: CH PAU
city: Perpignan
country: France
facility: CH Perpignan
city: Périgueux
country: France
facility: Centre Hospitalier de Périgueux
city: Reims
country: France
facility: CHU Reims
city: Saint-Lô
country: France
facility: CH Saint-Lô
city: Strasbourg
country: France
facility: CHRU Strasbourg Haute Pierre
city: Strasbourg
country: France
facility: CHU Strasbourg
city: Suresnes
country: France
facility: Hopital Foch
city: Tourcoing
country: France
facility: CH Tourcoing
city: Vannes
country: France
facility: CH Vannes
city: Villefranche-sur-Saône
country: France
facility: Hôpital Nord-Ouest de Villefranche sur Saone
city: Étampes
country: France
facility: CH Sud Essone
city: Saint-Denis
country: Réunion
facility: CHU La Réunion
Study officials:
affiliation: Centre Hospitalier Universitaire d'Orléans
name: Francois BARBIER, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
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