LB-5. DAV132 Protects Intestinal Microbiota of Patients Treated with Quinolones, a European Phase II Randomized Controlled Trial (SHIELD)
Notice bibliographique
Résumé
Abstract Background Antibiotics elicit intestinal dysbiosis with short and long-term deleterious effects. A colon-targeted adsorbent, DAV132, prevents dysbiosis in healthy humans and may protect antibiotic-treated patients. Methods Hospitalized patients receiving oral/iv fluoroquinolones (FQ) for the treatment of or prophylaxis of febrile neutropenia were randomized to receive DAV132 (7.5g tid orally), or not, during FQ receipt and followed up 51d. Plasma FQ levels were assessed at D4 (LC-MS/MS). Feces were collected during and up to 30d after FQ receipt for assessment of free fecal FQ levels (LC-MS/MS), gut microbiome α/β diversity (16S rRNA), resistance to colonization by C. difficile (Cd; ex-vivo proliferation). Relatedness of adverse events (AEs) to drugs was adjudicated by blinded independent experts. Results 243 patients from 23 sites, median age 71y, ≥1 chronic comorbidity 95%, received levofloxacin (43%), ciprofloxacin (40%) or moxifloxacin (18%) for (79% iv). During receipt, fecal FQ levels were lowered by >97% with DAV132 vs. No DAV132 (p< 0.0001), whilst plasma levels did not change significantly. Microbiome diversity was significantly protected with DAV132 using all metrics, e.g. the change from D1 of Shannon index at End-of-FQ (difference of means at End-of-FQ 0.42, 95% CI: 0.085; 0.752). The proportions of patients with DAV132- and/or FQ-related AEs (primary endpoint) did not differ significantly (14.8 vs. 10.8%, difference of proportions: 3.9%; 95% CI: -4.7; 12.6). No Cd infection occurred. Resistance to colonization by Cd was reduced in stools of patients receiving FQ only, but was maintained in those of patients who also received DAV132 (p=0.035). The acquisition of fecal carriage of vancomycin-resistant enterococci (VRE) was reduced with DAV132 (p=0.019). Figure 1: a. Free fluoroquinolones fecal concentration (mean ± SEM, µg/g) over time per FQ treatment group; b. Change of Shannon Index from baseline (mean ± SEM) over time Conclusion DAV132 was well tolerated in elderly hospitalized patients with comorbidities. It neither altered antibiotic plasma levels nor elicited changes in concomitant drugs regimens. Intestinal microbiota diversity was protected and resistance to colonization by Cd was preserved. DAV132 is a promising, novel product to prevent antibiotic-induced intestinal dysbiosis. Disclosures Annie Ducher, MD, Da Volterra (Employee, Shareholder) Maria J.G.T. Vehreschild, n/a, 3M (Grant/Research Support)Astellas Pharma (Grant/Research Support)Astellas Pharma (Consultant)Astellas Pharma (Speaker's Bureau)Basilea (Speaker's Bureau)Berlin Chemie (Consultant)Da Volterra (Grant/Research Support)Da Volterra (Grant/Research Support)Gilead (Grant/Research Support)Gilead (Speaker's Bureau)Merck/MSD (Speaker's Bureau)Merck/MSD (Grant/Research Support)MSD/Merck (Consultant)Organobalance (Grant/Research Support)Organobalance (Speaker's Bureau)Pfizer (Speaker's Bureau)Seres Therapeutics (Grant/Research Support) Thomas J. Louie, MD, Da Volterra (Consultant) Oliver A. Cornely, MD, Actelion (Consultant, Grant/Research Support, Speaker's Bureau)Al Jazeera Pharmaceuticals (Consultant)Allecra Therapeutics (Consultant, Grant/Research Support, Speaker's Bureau)Amplyx (Consultant, Grant/Research Support, Speaker's Bureau)Astellas (Consultant, Grant/Research Support, Speaker's Bureau)Basilea (Consultant, Grant/Research Support, Speaker's Bureau)Biosys UK Limited (Consultant, Grant/Research Support, Speaker's Bureau)Cidara (Consultant, Grant/Research Support, Speaker's Bureau)Da Volterra (Consultant, Grant/Research Support, Speaker's Bureau)Entasis (Consultant, Grant/Research Support, Speaker's Bureau)European Commission (Grant/Research Support)F2G (Consultant, Grant/Research Support, Speaker's Bureau)German Federal Ministry of Research andEducation (Grant/Research Support)Gilead (Consultant, Grant/Research Support, Speaker's Bureau)Grupo Biotoscana (Consultant, Grant/Research Support, Speaker's Bureau)Janssen Pharmaceuticals (Consultant, Grant/Research Support, Speaker's Bureau)Matinas (Consultant, Grant/Research Support, Speaker's Bureau)MedicinesCompany (Consultant, Grant/Research Support, Speaker's Bureau)MedPace (Consultant, Grant/Research Support, Speaker's Bureau)Melinta Therapeutics (Consultant, Grant/Research Support, Speaker's Bureau)Menarini Ricerche (Consultant, Grant/Research Support, Speaker's Bureau)Merck/MSD (Consultant, Grant/Research Support, Speaker's Bureau)Mylan Pharmaceuticals (Consultant)Nabriva (Consultant)Noxxon (Consultant)Octapharma (Consultant, Grant/Research Support, Speaker's Bureau)Paratek Pharmaceuticals (Consultant, Grant/Research Support, Speaker's Bureau)Pfizer (Consultant, Grant/Research Support, Speaker's Bureau)PSI (Consultant, Grant/Research Support, Speaker's Bureau)Roche Diagnostics (Consultant)Scynexis (Consultant, Grant/Research Support, Speaker's Bureau)Shionogi (Consultant) Céline Féger, PhD, Da Volterra (Consultant) Aaron Dane, MSc, Da Volterra (Consultant)Spero theraputics (Consultant) Aaron Dane, MSc, Spero theraputics (Consultant) Marina Varastet, PhD, Da Volterra (Employee) Jean de Gunzburg, PhD, Da Volterra (Board Member, Consultant, Shareholder) Antoine Andremont, PhD, Bioaster (Consultant)Da Volterra (Board Member, Consultant, Shareholder) France Mentré, MD, Da Volterra (Consultant)
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».