Title :

Pharmacokinetics and safety of aztreonam/avibactam for the treatment of complicated intra-abdominal infections in hospitalized adults: results from the REJUVENATE study

Author(s) :

Cornely, Oliver [Auteur]
University Hospital of Cologne [Cologne]
Cisneros, José [Auteur]
Torre-Cisneros, Julian [Auteur]
Universidad de Córdoba = University of Córdoba [Córdoba]
Rodríguez-Hernández, María Jesús [Auteur]
Tallón-Aguilar, Luis [Auteur]
Calbo, Esther [Auteur]
Universitat Autònoma de Barcelona = Autonomous University of Barcelona = Universidad Autónoma de Barcelona [UAB]
Horcajada, Juan [Auteur]
Queckenberg, Christian [Auteur]
Zettelmeyer, Ulrike [Auteur]
Arenz, Dorothee [Auteur]
Rosso-Fernández, Clara [Auteur]
Jiménez-Jorge, Silvia [Auteur]
Turner, Guy [Auteur]
Raber, Susan [Auteur]
O’brien, Seamus [Auteur]
Luckey, Alison [Auteur]
Aguado, Ana Cristina Padial [Auteur]
Baranda, Miguel Montejo [Auteur]
Bernedo, Carlos García [Auteur]
Bludau, Marc [Auteur]
Boix-Palop, Lucía [Auteur]
Cheng, Karen [Auteur]
de Jonge, Boudewijn [Auteur]
de Molina, Francisco Javier González [Auteur]
Gentil, Pilar Retamar [Auteur]
Guzmán-Puche, Julia [Auteur]
Jiménez, Virginia Palomo [Auteur]
López-Ruiz, José [Auteur]
Mateos, Enrique Montero [Auteur]
Oporto, Cristina Roca [Auteur]
Piessen, Guillaume [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Postil, Deborah [Auteur]
Rodríguez, Rosa [Auteur]
Ruiz, Javier Padillo [Auteur]
Rupp, Jan [Auteur]
Soriano, Rafael Morales [Auteur]
Wible, Michele [Auteur]
Yuste, Ángela Cano [Auteur]
Gómez-Zorrilla, Silvia [Auteur]

Journal title :

Journal of Antimicrobial Chemotherapy

Pages :

618-627

Publisher :

Oxford University Press (OUP)

Publication date :

2020-03-01

ISSN :

0305-7453

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer

English abstract : [en]

Abstract Objectives To investigate pharmacokinetics (PK) and safety (primary objectives) and efficacy (secondary objective) of the investigational monobactam/β-lactamase inhibitor combination aztreonam/avibactam in patients ...
Show more >Abstract Objectives To investigate pharmacokinetics (PK) and safety (primary objectives) and efficacy (secondary objective) of the investigational monobactam/β-lactamase inhibitor combination aztreonam/avibactam in patients with complicated intra-abdominal infection (cIAI). Methods This Phase 2a open-label, multicentre study (NCT02655419; EudraCT 2015-002726-39) enrolled adults with cIAI into sequential cohorts for 5–14 days treatment. Cohort 1 patients received an aztreonam/avibactam loading dose of 500/137 mg (30 min infusion), followed by maintenance doses of 1500/410 mg (3 h infusions) q6h; Cohort 2 received 500/167 mg (30 min infusion), followed by 1500/500 mg (3 h infusions) q6h. Cohort 3 was an extension of exposure at the higher dose regimen. Doses were adjusted for creatinine clearance of 31–50 mL/min (Cohorts 2 + 3). All patients received IV metronidazole 500 mg q8h. PK, safety and efficacy were assessed. Results Thirty-four patients (Cohort 1, n = 16; Cohorts 2 + 3, n = 18) comprised the modified ITT (MITT) population. Mean exposures of aztreonam and avibactam in Cohorts 2 + 3 were consistent with those predicted to achieve joint PK/pharmacodynamic target attainment in >90% patients. Adverse events (AEs) were similar between cohorts. The most common AEs were hepatic enzyme increases [n = 9 (26.5%)] and diarrhoea [n = 5 (14.7%)]. Clinical cure rates at the test-of-cure visit overall were 20/34 (58.8%) (MITT) and 14/23 (60.9%) (microbiological-MITT population). Conclusions Observed AEs were consistent with the known safety profile of aztreonam monotherapy, with no new safety concerns identified. These data support selection of the aztreonam/avibactam 500/167 mg (30 min infusion) loading dose and 1500/500 mg (3 h infusions) maintenance dose q6h regimen, in patients with creatinine clearance >50 mL/min, for the Phase 3 development programme.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL