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Impact on the Gut Microbiota of Intensive and Prolonged Antimicrobial Therapy in Patients With Bone and Joint Infection

Authors :
Benoît Levast
Nicolas Benech
Cyrielle Gasc
Cécile Batailler
Eric Senneville
Sébastien Lustig
Cécile Pouderoux
David Boutoille
Lilia Boucinha
Frederic-Antoine Dauchy
Valérie Zeller
Marianne Maynard
Charles Cazanave
Thanh-Thuy Le Thi
Jérôme Josse
Joël Doré
Frederic Laurent
Tristan Ferry
MaaT Pharma [Lyon]
Université Claude Bernard Lyon 1 (UCBL)
Université de Lyon
Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL]
Hôpital de la Croix-Rousse [CHU - HCL]
Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)
Hospices Civils de Lyon (HCL)
Service de Chirurgie Orthopédique [Centre Albert Trillat]
Centre Albert Trillat [Hôpital de la Croix-Rousse - HCL]
Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL]
Université de Lille
Service Régional Universitaire des Maladies Infectieuses et du Voyageur
Centre Hospitalier de Tourcoing
Université de Nantes (UN)
Bordeaux population health (BPH)
Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
USC EA 3671, infections humaines à mycoplasmes et chlamydiae
Université de Bordeaux (UB)-Institut National de la Recherche Agronomique (INRA)
Centre International de Recherche en Infectiologie - UMR (CIRI)
Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)
MICrobiologie de l'ALImentation au Service de la Santé (MICALIS)
AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
MetaGenoPolis (MGP (US 1367))
Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
This study was funded by MaaT Pharma (http://www.maatpharma.com) as part of the Concours Mondial de l'Innovation funded by Banque Publique d'Investissement-France.
Institut National de la Recherche Agronomique (INRA)-Université de Bordeaux (UB)
Centre International de Recherche en Infectiologie (CIRI)
École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Source :
Frontiers in Medicine, Frontiers in Medicine, Frontiers media, 2021, 8 (586875), ⟨10.3389/fmed.2021.586875⟩, Frontiers in Medicine, Vol 8 (2021), Frontiers in Medicine, 2021, 8 (586875), ⟨10.3389/fmed.2021.586875⟩
Publication Year :
2021

Abstract

There is a growing interest in the potentially deleterious impact of antibiotics on gut microbiota. Patients with bone and joint infection (BJI) require prolonged treatment that may impact significantly the gut microbiota. We collected samples from patients with BJI at baseline, end of antibiotics (EOT), and 2 weeks after antibiotic withdrawal (follow-up, FU) in a multicenter prospective cohort in France. Microbiota composition was determined by shotgun metagenomic sequencing. Fecal markers of gut permeability and inflammation as well as multi-drug-resistant bacteria (MDRB) and Clostridioides difficile carriage were assessed at each time point. Sixty-two patients were enrolled: 27 native BJI, 14 osteosynthesis-related BJI, and 21 prosthetic joint infections (PJI). At EOT, there was a significant loss of alpha-diversity that recovered at FU in patients with native BJI and PJI, but not in patients with osteosynthesis-related BJI. At EOT, we observed an increase of Proteobacteria and Bacteroidetes that partially recovered at FU. The principal component analysis (PCoA) of the Bray–Curtis distance showed a significant change of the gut microbiota at the end of treatment compared to baseline that only partially recover at FU. Microbiota composition at FU does not differ significantly at the genus level when comparing patients treated for 6 weeks vs. those treated for 12 weeks. The use of fluoroquinolones was not associated with a lower Shannon index at the end of treatment; however, the PCoA of the Bray–Curtis distance showed a significant change at EOT, compared to baseline, that fully recovered at FU. Levels of fecal neopterin were negatively correlated with the Shannon index along with the follow-up (r2 = 0.17; p < 0.0001). The PCoA analysis of the Bray–Curtis distance shows that patients with an elevated plasma level of C-reactive protein (≥5 mg/L) at EOT had a distinct gut microbial composition compared to others. MDRB and C. difficile acquisition at EOT and FU represented 20% (7/35) and 37.1% (13/35) of all MDRB/C. difficile-free patients at the beginning of the study, respectively. In patients with BJI, antibiotics altered the gut microbiota diversity and composition with only partial recovery, mucosal inflammation, and permeability and acquisition of MDRB carriage. Microbiome interventions should be explored in patients with BJI to address these issues.

Details

Language :
English
ISSN :
2296858X
Database :
OpenAIRE
Journal :
Frontiers in Medicine, Frontiers in Medicine, Frontiers media, 2021, 8 (586875), ⟨10.3389/fmed.2021.586875⟩, Frontiers in Medicine, Vol 8 (2021), Frontiers in Medicine, 2021, 8 (586875), ⟨10.3389/fmed.2021.586875⟩
Accession number :
edsair.doi.dedup.....e1d3f971d91597acbf721d9e8992f75c