Antimicrobial Therapy for Difficult-to-treat Pseudomonas Aeruginosa

Официальное название

Antimicrobial Therapy for Infections Due to Pseudomonas Aeruginosa With Difficult-to-treat Resistance: a Real-world, Prospective, Multicenter Cohort Study

Обзор

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.

Подробное описание

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).

Первичные конечные точки

• Clinical cure rate [Срок оценки: Test of cure visit]
• Clinical cure [Срок оценки: Day 7±2 after the completion of definite therapy]

Вторичные конечные точки (8)

• Microbiological eradication [Срок оценки: Day 7]
• Resistance emergence [Срок оценки: Up to hospital discharge, an average of 1 month]
• Non-ecological adverse events [Срок оценки: At test-of-cure visit, 7±2 days after the completion of definite therapy]
• Non-ecological adverse events [Срок оценки: From the first day of definite therapy to the ToC visit]
• Acquisition of multidrug-resistant bacteria other than DTR P. aeruginosa [Срок оценки: Up to hospital discharge, an average of 1 month]
• Clostridioides difficile infection [Срок оценки: Up to hospital discharge, an average of 1 month]
• In-hospital death [Срок оценки: Up to hospital discharge, an average of 1 month]
• Death at Day 28 [Срок оценки: Day 28]

Критерии участия

Критерии включения

• All patients aged 18 or over and requiring intravenous definite antimicrobial therapy for a DTR P. aeruginosa infection

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 47 центров

• CHU Amiens — Amiens
• CH Argenteuil — Argenteuil
• CH Bayonne — Bayonne
• CHU de BESANCON — Besançon
• CH Bethune — Béthune
• CHU Avicenne — Bobigny
• CH Bourgoin-Jallieu — Bourgoin
• CH Métropole Savoie — Chambéry
• … и ещё 39 центров

Reunion · 1 центр

• CHU La Réunion — Saint-Denis

Публикации

• 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/c PMID 35439291
• 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. PMID 31478103
• 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 PMID 31704217
• 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 PMID 31676155
• 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: PMID 34671728
• 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 2 PMID 36590586
• 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 bloo PMID 36764959

Идентификаторы

NCT: NCT06738771 · 2023-HORS RIPH-11

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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