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

Frontiers in Medicine

Frederic-Antoine Dauchy¹  Charles Cazanave²  Marianne Maynard³  Thanh-Thuy Le Thi⁴  Benoît Levast⁵  Lilia Boucinha⁵  Cyrielle Gasc⁵  David Boutoille⁶  Eric Senneville⁷  Valérie Zeller⁸  Cécile Pouderoux⁹  Tristan Ferry^1,10  Nicolas Benech^1,11  Jérôme Josse^1,12  Frederic Laurent^1,12  Sébastien Lustig^1,13  Cécile Batailler^1,13  Joël Doré^1,14 

[1] Centre Hospitalier Universitaire de Bordeaux, Service des Maladies Infectieuses et Tropicales, Hôpital Pellegrin, CHU de Bordeaux, Centre de référence des Infections Ostéoarticulaires Complexes du Grand Sud-Ouest (CRIOAc GSO), Bordeaux, France;Centre Hospitalier Universitaire de Bordeaux, Service des Maladies Infectieuses et Tropicales, Hôpital Pellegrin, CHU de Bordeaux, Centre de référence des Infections Ostéoarticulaires Complexes du Grand Sud-Ouest (CRIOAc GSO), Bordeaux, France;Univ. Bordeaux, USC EA 3671, Infections Humaines à Mycoplasmes et à Chlamydiae, Bordeaux, France;Centre de Recherche Clinique, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Centre de Ressource Biologique, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;MaaT Pharma, Lyon, France;Service de Maladies Infectieuses et Tropicales, Hôpital de l'Hôtel-Dieu, CHU de Nantes, Nantes, France;Université de Nantes, Nantes, France;Centre de Référence des Infections Ostéo-Articulaires Grand-Ouest, Nantes, France;Service de Maladies Infectieuses et du Voyageur, Centre Hospitaliser Gustave Dron, Tourcoing, France;Université de Lille, Lille, France;Centre de Référence Pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lille-tourcoing), Tourcoing, France;Service de Médecine Interne et Rhumatologie, GH Diaconesses-Croix Saint-Simon, Paris, France;Centre de Référence Infections Ostéoarticulaires Complexes de Paris (CRIOAc Paris), Paris, France;Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Centre de Référence Pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Université Claude Bernard Lyon 1, Lyon, France;Centre de Référence Pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;CIRI – Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France;Service des Maladies Infectieuses et Tropicales, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Université Claude Bernard Lyon 1, Lyon, France;Centre de Référence Pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;TGF-ß Immune Evasion, Tumor Escape Resistance Immunity Department, Cancer Research Center of Lyon, Inserm 1052, CNRS 5286, Lyon, France;Université Claude Bernard Lyon 1, Lyon, France;Centre de Référence Pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;Institut des Agents Infectieux, Laboratoire de Bactériologie, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;CIRI – Centre International de Recherche en Infectiologie, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Univ Lyon, Lyon, France;Université Claude Bernard Lyon 1, Lyon, France;Centre de Référence Pour la Prise en Charge des Infections Ostéo-Articulaires Complexes (CRIOAc Lyon), Hospices Civils de Lyon, Lyon, France;Service de Chirurgie Orthopédique, Hôpital de la Croix-Rousse, Hospices Civils de Lyon, Lyon, France;Université Paris-Saclay, INRAE, MetaGenoPolis, AgroParisTech, MICALIS, Jouy-en-Josas, France;

关键词: gut microbiota;    antimicrobial therapy;    antibiotics;    bone and joint infection;    dysbiosis;   

DOI  :  10.3389/fmed.2021.586875

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

CC BY