Universität zu Köln

Vehreschild, Maria J. G. T., Ducher, Annie, Louie, Thomas, Cornely, Oliver A. ORCID: 0000-0001-9599-3137, Feger, Celine, Dane, Aaron, Varastet, Marina, Vitry, Fabien, de Gunzburg, Jean, Andremont, Antoine, Mentre, France ORCID: 0000-0002-7045-1275 and Wilcox, Mark H. (2022). An open randomized multicentre Phase 2 trial to assess the safety of DAV132 and its efficacy to protect gut microbiota diversity in hospitalized patients treated with fluoroquinolones. J. Antimicrob. Chemother., 77 (4). S. 1155 - 1166. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Background DAV132 (colon-targeted adsorbent) has prevented antibiotic-induced effects on microbiota in healthy volunteers. Objectives To assess DAV132 safety and biological efficacy in patients. Patients and methods An open-label, randomized [stratification: fluoroquinolone (FQ) indication] multicentre trial comparing DAV132 (7.5 g, 3 times a day, orally) with No-DAV132 in hospitalized patients requiring 5-21 day treatment with FQs and at risk of Clostridioides difficile infection (CDI). FQ and DAV132 were started simultaneously, DAV132 was administered for 48 h more, and patients were followed up for 51 days. The primary endpoint was the rate of adverse events (AEs) independently adjudicated as related to DAV132 and/or FQ. The planned sample size of 260 patients would provide a 95% CI of +/- 11.4%, assuming a 33% treatment-related AE rate. Plasma and faecal FQ concentrations, intestinal microbiota diversity, intestinal colonization with C. difficile, MDR bacteria and yeasts, and ex vivo resistance to C. difficile faecal colonization were assessed. Results Two hundred and forty-three patients (median age 71 years; 96% with chronic comorbidity) were included (No-DAV132, n = 120; DAV132, n = 123). DAV132- and/or FQ-related AEs did not differ significantly: 18 (14.8%) versus 13 (10.8%) in DAV132 versus No-DAV132 patients (difference 3.9%; 95% CI: -4.7 to 12.6). Day 4 FQ plasma levels were unaffected. DAV132 was associated with a >98% reduction in faecal FQ levels (Day 4 to end of treatment; P < 0.001), less impaired microbiota diversity (Shannon index; P = 0.003), increased ex vivo resistance to C. difficile colonization (P = 0.0003) and less frequent FQ-induced VRE acquisition (P = 0.01). Conclusions In FQ-treated hospitalized patients, DAV132 was well tolerated, and FQ plasma concentrations unaffected. DAV132 preserved intestinal microbiota diversity and C. difficile colonization resistance.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vehreschild, Maria J. G. T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Ducher, Annie UNSPECIFIED UNSPECIFIED UNSPECIFIED Louie, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Cornely, Oliver A. UNSPECIFIED orcid.org/0000-0001-9599-3137 UNSPECIFIED Feger, Celine UNSPECIFIED UNSPECIFIED UNSPECIFIED Dane, Aaron UNSPECIFIED UNSPECIFIED UNSPECIFIED Varastet, Marina UNSPECIFIED UNSPECIFIED UNSPECIFIED Vitry, Fabien UNSPECIFIED UNSPECIFIED UNSPECIFIED de Gunzburg, Jean UNSPECIFIED UNSPECIFIED UNSPECIFIED Andremont, Antoine UNSPECIFIED UNSPECIFIED UNSPECIFIED Mentre, France UNSPECIFIED orcid.org/0000-0002-7045-1275 UNSPECIFIED Wilcox, Mark H. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-691245
DOI:	10.1093/jac/dkab474
Journal or Publication Title:	J. Antimicrob. Chemother.
Volume:	77
Number:	4
Page Range:	S. 1155 - 1166
Date:	2022
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2091
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VANCOMYCIN-RESISTANT ENTEROCOCCI; BETA-LACTAMASE; INTESTINAL COLONIZATION; ANTIBIOTIC EXPOSURE; THERAPY; DISRUPTION; PREVENTION; DYSBIOSIS; ADSORBENT; BACTERIA Multiple languages Infectious Diseases; Microbiology; Pharmacology & Pharmacy Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69124