PMID- 35016205
OWN - NLM
STAT- MEDLINE
DCOM- 20220401
LR  - 20220602
IS  - 1460-2091 (Electronic)
IS  - 0305-7453 (Print)
IS  - 0305-7453 (Linking)
VI  - 77
IP  - 4
DP  - 2022 Mar 31
TI  - 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.
PG  - 1155-1165
LID - 10.1093/jac/dkab474 [doi]
AB  - 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.
CI  - (c) The Author(s) 2022. Published by Oxford University Press on behalf of British 
      Society for Antimicrobial Chemotherapy.
FAU - Vehreschild, Maria J G T
AU  - Vehreschild MJGT
AD  - Department of Internal Medicine, Infectious Diseases, University Hospital 
      Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany.
FAU - Ducher, Annie
AU  - Ducher A
AD  - Da Volterra, Paris, France.
FAU - Louie, Thomas
AU  - Louie T
AD  - Cumming School of Medicine, University of Calgary, Calgary, Canada.
FAU - Cornely, Oliver A
AU  - Cornely OA
AD  - Faculty of Medicine and University Hospital Cologne, Department I of Internal 
      Medicine, Excellence Center for Medical Mycology (ECMM), University of Cologne, 
      Cologne, Germany.
AD  - Faculty of Medicine and University Hospital Cologne, Chair Translational 
      Research, Cologne Excellence Cluster on Cellular Stress Responses in 
      Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany.
AD  - Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre 
      Cologne (ZKS Koln), University of Cologne, Cologne, Germany.
AD  - German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, 
      Germany.
FAU - Feger, Celine
AU  - Feger C
AD  - Da Volterra, Paris, France.
AD  - EMIBiotech, Paris, France.
FAU - Dane, Aaron
AU  - Dane A
AD  - Danestat, Macclesfield, UK.
FAU - Varastet, Marina
AU  - Varastet M
AD  - Da Volterra, Paris, France.
FAU - Vitry, Fabien
AU  - Vitry F
AD  - Da Volterra, Paris, France.
FAU - de Gunzburg, Jean
AU  - de Gunzburg J
AD  - Da Volterra, Paris, France.
FAU - Andremont, Antoine
AU  - Andremont A
AD  - Da Volterra, Paris, France.
AD  - Universite de Paris, IAME, INSERM U1137, Paris, France.
FAU - Mentre, France
AU  - Mentre F
AD  - Universite de Paris, IAME, INSERM U1137, Paris, France.
FAU - Wilcox, Mark H
AU  - Wilcox MH
AUID- ORCID: 0000-0002-4565-2868
AD  - Leeds Institute of Medical Research, University of Leeds and Leeds Teaching 
      Hospitals, Leeds, UK.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Antimicrob Chemother
JT  - The Journal of antimicrobial chemotherapy
JID - 7513617
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Fluoroquinolones)
SB  - IM
MH  - Aged
MH  - Anti-Bacterial Agents/adverse effects
MH  - *Clostridioides difficile
MH  - *Clostridium Infections/drug therapy/prevention & control
MH  - Fluoroquinolones/adverse effects
MH  - *Gastrointestinal Microbiome
MH  - Humans
PMC - PMC8969469
EDAT- 2022/01/12 06:00
MHDA- 2022/04/02 06:00
PMCR- 2022/01/07
CRDT- 2022/01/11 20:20
PHST- 2021/07/05 00:00 [received]
PHST- 2021/11/19 00:00 [accepted]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/04/02 06:00 [medline]
PHST- 2022/01/11 20:20 [entrez]
PHST- 2022/01/07 00:00 [pmc-release]
AID - 6500724 [pii]
AID - dkab474 [pii]
AID - 10.1093/jac/dkab474 [doi]
PST - ppublish
SO  - J Antimicrob Chemother. 2022 Mar 31;77(4):1155-1165. doi: 10.1093/jac/dkab474.