Titre :

Safety and tolerability of a single administration of AR-301, a human monoclonal antibody, in ICU patients with severe pneumonia caused by Staphylococcus aureus: first-in-human trial.

Auteur(s) :

Francois, Bruno [Auteur]
Centre d'Investigation Clinique de Limoges [CIC1435]
Mercier, Emmanuelle [Auteur]
Gonzalez, Celine [Auteur]
Asehnoune, Karim [Auteur]
Nseir, Saad [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Fiancette, Maud [Auteur]
Desachy, Arnaud [Auteur]
Plantefeve, Gaetan [Auteur]
Meziani, Ferhat [Auteur]
Université de Strasbourg [UNISTRA]
De Lame, Paul-Andre [Auteur]
Laterre, Pierre-Francois [Auteur]

Titre de la revue :

Intensive Care Medicine

Nom court de la revue :

Intensive Care Med.

Numéro :

44

Pagination :

1787–1796

Date de publication :

2018-11

Mot(s)-clé(s) :

HAP
Staphylococcus aureus
Monoclonal antibody
Adjunctive therapy
VAP

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

Purpose: Hospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus ...
Lire la suite >Purpose: Hospital-acquired bacterial pneumonia (HABP) is a critical concern in hospitals with ventilator-associated bacterial pneumonia (VABP) remaining the most common infection in the ICU, often due to Staphylococcus aureus, an increasingly difficult to treat pathogen. Anti-infective monoclonal antibodies (mAb) may provide new, promising treatment options. This randomized, double-blinded, placebo-controlled study aimed at assessing the safety and pharmacokinetics of AR-301, an S. aureus alpha toxin-neutralizing mAb, and exploring its clinical and microbiologic outcomes when used adjunctively with standard-of-care antibiotics. Methods: Eligibility in this trial required microbiologically confirmed severe S. aureus pneumonia, including HABP, VABP or CABP, treated in the ICU and an APACHE II score ≤ 30. Standard-of-care antibiotics selected by the investigators were administered to all patients in the study following clinical and microbiologic confirmation of S. aureus pneumonia. Adjunctive treatment of AR-301 was to start < 36 h after onset of severe pneumonia. AR-301 was administered to four sequentially ascending dose cohorts. The placebo cohort received antibiotics and a placebo buffer. Clinical outcomes were adjudicated by a blinded committee. S. aureus eradication was declared based on a negative follow-up culture and presumed to be negative when no culture was obtained in the presence of clinical improvement. Results: Thirteen ICUs enrolled 48 patients, with pneumonia attributable to MRSA in six subjects. The study drug displayed a favorable safety profile: Of 343 AEs reported, 8 (2.3%) were deemed related, none serious. In a post hoc subgroup analysis of VABP patients receiving AR-301, ventilation duration was shorter for AR-301-treated patients compared with the placebo group. Overall, there was a trend toward a better and faster microbiologic eradication at day 28. The PK profile of AR-301 is consistent with that of a human IgG1 mAb, with a plasma half-life of about 25 days. Conclusions: Adjunctive treatment of severe S. aureus HABP with anti-staphylococcal mAbs appears feasible and suggests some clinical benefits, but larger randomized studies are needed to better define its safety and efficacy.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Inserm
Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Équipe(s) de recherche :

Fungal associated invasive and inflammatory diseases
Glycation from inflammation to aging

Date de dépôt :

2019-03-01T14:34:30Z
2021-05-18T06:16:41Z
2023-12-13T10:27:53Z