Papers by Didier Lepelletier
HAL (Le Centre pour la Communication Scientifique Directe), Sep 10, 2021
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Antimicrobial Resistance and Infection Control, Jun 16, 2015
Journal of Clinical Microbiology, May 1, 2011
We describe the first case of hip prosthetic infection due to Lactococcus garvieae. The patient, ... more We describe the first case of hip prosthetic infection due to Lactococcus garvieae. The patient, a 71-year-old woman fishmonger, developed a hip infection 7 years after total hip arthroplasty. The origin of infection was possibly due to the manipulation or intake of seafood or fish contaminated with Lactococcus garvieae.

PLOS ONE, Apr 25, 2017
Objectives Several automated algorithms for epidemiological surveillance in hospitals have been p... more Objectives Several automated algorithms for epidemiological surveillance in hospitals have been proposed. However, the usefulness of these methods to detect nosocomial outbreaks remains unclear. The goal of this review was to describe outbreak detection algorithms that have been tested within hospitals, consider how they were evaluated, and synthesize their results. Methods We developed a search query using keywords associated with hospital outbreak detection and searched the MEDLINE database. To ensure the highest sensitivity, no limitations were initially imposed on publication languages and dates, although we subsequently excluded studies published before 2000. Every study that described a method to detect outbreaks within hospitals was included, without any exclusion based on study design. Additional studies were identified through citations in retrieved studies. Results Twenty-nine studies were included. The detection algorithms were grouped into 5 categories: simple thresholds (n = 6), statistical process control (n = 12), scan statistics (n = 6), traditional statistical models (n = 6), and data mining methods (n = 4). The evaluation of the algorithms was often solely descriptive (n = 15), but more complex epidemiological criteria were also investigated (n = 10). The performance measures varied widely between studies: e.g., the sensitivity of an algorithm in a real world setting could vary between 17 and 100%.

Archives of public health, Aug 19, 2022
Background: In order to understand the pandemic COVID-19 crisis in a forward-looking way, the Fre... more Background: In order to understand the pandemic COVID-19 crisis in a forward-looking way, the French High Council for public health (HCSP) has designed a conceptual scheme for public health planning based on L. Green's model in order to better understand the issues at stake, by identifying dangers and levers for action. The final aim was to establish priorities and guidelines in order to anticipate the collateral consequences of the management of the crisis and be better prepared for the next one. Method: A public health conceptual framework PRECEDE-PROCEED adapted to the Covid-19 health crisis was developed using both a graphic (concept map) and analytic (to make the conceptual scheme functional) approaches. Then, a "meta-method" was applied using three distinct cognitive stages: understanding, anticipation and proposals of action. Results: The conceptual framework was broken down into 10 technical sheets covering essential diagnoses and integrating different public health determinants. Each of these was broken down into three cognitive stages, allowing for a diagnosis of understanding, a scenario of anticipation and a strategic analysis of action according to the chronology: understand-anticipate-propose. From these 10 technical sheets, 32 guidelines have been proposed. Conclusion: This work is intended to allow reflections on public health approaches to strengthen and anticipate health crisis management and health planning by politic managers working at national or sub-national level.

Research Square (Research Square), Apr 14, 2020
Background: Almost 15 % of patients with ulcerative colitis (UC) will require a proctocolectomy w... more Background: Almost 15 % of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch-anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UCassociated pouchitis. However, currently there is no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis. Methods Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation. Discussion: On April 30, 2014, WHO published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future. Trial registration: The trial, published on May 14, 2018, is registered at ClinicalTrials.Gov under registration number NCT03524352: https://clinicaltrials.gov/ct2/show/NCT03524352?term=NCT03524352&rank=1 Background double-blind label study of the prophylaxis of recurrent pouchitis after fecal microbiota transplant in UC with ileo-anal anastomosis" by peer-review, of which Dr. Trang is the coordinating investigator. This grant is allocated following peer review. The research projects selected by this call for tenders must contribute to medical progress and the improvement of the health care system. The experts' comments have been taken into account in the final protocol submitted to the regulatory authorities. All the publications, of this trial, funded by the French Ministry of Health, must clearly identify the coordinating health institution and must be marked: "This study was supported by a grant from the French Ministry of Health POCA, 2016, PHRC 16-267". However, the funding body did not and will not play role in the design of the study and collection, analysis and interpretation of date and in writing the manuscripts.
HAL (Le Centre pour la Communication Scientifique Directe), Sep 25, 2020
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. AVIS relatif à l'adaptation de la doctrine du HCSP et des mesures barrières et au port de masque, notamment dans les établissements recevant du public et aux grands rassemblements sportifs et culturels, dans le cadre de la pandémie de Covid-19 (HCSP, Avis et Rapports)

Staphylokinase and Abo Group Phenotype: New Players of Host-Pathogen Interaction in Staphylococcus Aureus Implant-Associated Infections
Orthopaedic Proceedings, Feb 21, 2018
Staphylococcus aureus is a leading cause of implant-associated infections (IAI). The aim of this ... more Staphylococcus aureus is a leading cause of implant-associated infections (IAI). The aim of this study was to identify bacterial and/or clinical features involved in the pathogenesis of S. aureus IAI. 57 IAI S. aureus and 31 nasal carriage (NC) S. aureus isolates were studied. S. aureus genetic background was obtained by microarray analysis. Multi-Locus Sequence Typing was performed to determine clonal complexes (CC). The ability of S. aureus isolates to produce biofilm was investigated by resazurin and crystal violet methods. Clinical data were retrospectively collected from the patient9s medical records. Fifty-five IAI patients were included. Two of them had two different S. aureus IAI episodes. The median age was 73 years (range: 21–96 years) with 29 women (52.7%). The main diagnosis for arthroplasty was arthrosis (38%). Implants were hip prosthesis (n=35), knee prosthesis (n=18) and osteosynthesis (n=4). Infectious and nasal carriage isolates belonged respectively to 18 and 13 different sequence types (STs) without significant difference. Among IAI isolates, five strains were methicillin resistant. IAI isolates were classified as strong (14%), moderate (42.1%) and weak (43.9%) biofilm producers. For NC isolates, distribution was 12.9%, 25.8% and 61.3% for strong, moderate and weak, respectively. Staphylokinase gene was associated with the occurrence of S. aureus IAI (p Our results suggested that occurrence of IAI may depend on patients’ ABO blood group and staphylokinase gene detection. We also observed a strong biofilm producer phenotype in CC8 S. aureus. Further studies are needed to prove whether one bbp gene variant is correlated to this phenotype. This study was supported by a grant number WS1106649 from Pfizer, France and by the French “Ministere de l9Enseignement Superieur et de la Recherche”.

Impact of Virulence Genetic Background and Phylogeny of Propionibacterium Acnes Involved in Spine-Related, Prosthesis-Associated Infections and Acne Lesions
Orthopaedic Proceedings, Feb 21, 2018
Propionibacterium acnes is an emerging pathogen especially in orthopedic implant infection. Aim o... more Propionibacterium acnes is an emerging pathogen especially in orthopedic implant infection. Aim of this study was to investigate P. acnes phylogeny and to screen for virulence factors among a large collection of clinical isolates involved in spine material infections, arthroplasty infections and acne lesions. 88 P. acnes clinical isolates were collected between January 2003 and December 2014 at Nantes University Hospital (France). Fifty-eight isolates came from spine infections, 14 from prosthetic infections (knee, hip or shoulder), 14 from acne lesions and two reference strains (ATCC11827 and ATCC6919). Implant associated infections were confirmed using Infectious Diseases Society of America criteria for bone and joint infections. Phylotypes and Multi-Locus Sequence Typing (MLST) was carried out on all isolates as described by Lomholt et al. All isolates were tested by established PCR-based assays for 21 putative virulence factor genes characteristic of P. acnes. MLST analysis revealed an association between clonal complexes (CCs) and origin of P. acnes isolates (p = 0,027). Regarding CCs distribution between different origins, CC36 and phylotype II P. acnes isolates are more frequently observed in prosthetic joint infections. On the other hand, CC18 (IA) and CC28 (IB) P. acnes isolates are more frequently involved in spine infections and acne lesions. Among all virulence factors screened, hyaluronate lyase gene was only present in CC36 and phylotype II P acnes isolates. Other virulence factors were present in all isolates, whatever their origin or CC. Regarding molecular typing results, P. acnes involved in spine infections seem to have a skin origin (same CC as isolates from acne lesion). Interestingly, the origin of prosthetic joint infection isolates seems different and they all carry one more virulence factor. Hyaluronate lyase (Hyl) is a major surface protein of P. acnes with potential antigenetically variable properties that might be essential for P. acnes virulence. Increased tissue permeability caused by the action of hyaluronidase on the extracellular matrix appears to play a role in wound infections, pneumonia, and other sepsis such as bacteremia and meningitis. It could be also take a prominent part in P. acnes prosthetic joint infection pathogenesis.

Internalisation of Propionibacterium Acnes by Osteoblasts Depends on P. Acnes Genetic Background
Journal of Bone and Joint Surgery-british Volume, Dec 1, 2016
Aim Propionibacterium acnes is an emerging pathogen especially in orthopedic implant infection. I... more Aim Propionibacterium acnes is an emerging pathogen especially in orthopedic implant infection. Interestingly, we previously reported a difference in the distribution of the clades involved in spine versus hip or knee prosthetic infection. To date, no study has previously explored the direct impact and close relationship of P. acnes on bone cells according to their own genetic background. The aim of this study was to investigate this interaction of P. acnes clinical strains involved in spine material infections, arthroplasty infections and acne lesions with bone cells. Method From a large collection of 88 P. acnes clinical isolates collected between January 2003 and December 2014, a subset of 11 isolates was studied. Four isolates were recovered from spine infections, two from prosthetic infections (knee and hip), three from acne lesions and two reference strains (ATCC11827 and ATCC6919). Implant-associated infections were confirmed according to Infectious Diseases Society of America guidelines for bone and joint infections. Multi-Locus Sequence Typing (MLST) was carried out on all isolates as described by Lomholt et al . PLoS ONE 2010. Bacterial internalization experiments with MG63 osteosarcoma cells were adapted from Cremet et al. Pathog Dis 2015. Results Among the nine clinical isolates, three isolates belonged to clonal complexes (CCs) 18; three to CC28 and three to CC36. ATCC isolates belonged to CC18. Bacterial internalization experiments revealed that CC36 P. acnes strains were less invasive than CC18 and CC28 P. acnes strains towards osteoblasts (mean percentage of internalized bacteria ( P. acnes strains versus more than 1% for the CC18 and CC28 P. acnes strains). Surprisingly, the ATCC11827 CC18 P. acnes strain exhibited invasiveness similar to CC36 isolates. Conclusions Evasion mechanism observed for CC36 P. acnes isolates could allow this clade to leave the site of infection, disseminate into deeper tissue layers and beget arthroplasty infection. Inside the deeper tissue, close to the material, the local immune defect fosters the low-grade infections observed with P. acnes clinical strains . On the another hand, for CC18 et CC28 clades, mostly involved in spine infection, the internalization process observed could allow these clades to escape from the numerous immune cells located under the skin and generate an infection locally, favored by the spine instrumentation close to the skin, especially during long spine surgeries.
Facteurs associés aux infections du tractus urinaire à entérobactéries productrices de bêtalactamases à spectre étendu : étude de cas témoins chez des patients greffés rénaux entre 2008 et 2012 au CHU de Nantes
Nephrologie & Therapeutique, Sep 1, 2013
Hygiène - Étude Sur La Consommation De Produits Hydro-Alcooliques
Day surgery: should we be worried about the occurrence of surgical site infection in outpatients?
Journal of Hospital Infection, Aug 1, 2021
Retrospective analysis of a large single cohort of Enterobacteriaceae producing extended-spectrum B-lactamase (E-ESBL) patients: incidence, microbiology, and mortality
European Journal of Clinical Microbiology & Infectious Diseases, Sep 2, 2022
Journal of Hospital Infection, May 1, 2019
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Distributed under a Creative Commons Attribution-NonCommercial| 4.0 International License
Enterobacter cloacae complex outbreak in a neonatal intensive care unit: multifaceted investigations and preventive measures are needed
Journal of Hospital Infection, Oct 1, 2021
We report the investigation to control an Enterobacter cloacae complex outbreak in a NICU from No... more We report the investigation to control an Enterobacter cloacae complex outbreak in a NICU from November 2020 to February 2021. Pulsed-field gel electrophoresis showed that 5/8 cases were infected with a clonal strain. Breast pumps, shared among mothers in the unit, could have contributed to the spread of the clonal spread.

Surveillance et Contrôle Des Infections a Staphylococcus Aureus Resistants a La Meticilline Dans Les Hôpitaux Francais
L’emergence d’infections causees par des souches bacteriennes multiresistantes pose un probleme d... more L’emergence d’infections causees par des souches bacteriennes multiresistantes pose un probleme de sante publique qu’il devient urgent de maitriser du fait de leurs consequences en terme de morbidite, de mortalite et de cout [1,2]. Les Staphylococcus aureus resistants a la meticilline (SARM) sont devenus une des premieres causes d’infections nosocomiales dans les hopitaux du monde entier. Cependant, peu de donnees sont disponibles sur la frequence de ces infections au niveau national et sur les methodes utilisees par les hopitaux pour surveiller et controler ces infections [3]. Les objectifs de cette etude etaient d’evaluer les strategies utilisees par les hopitaux francais pour surveiller et controler les infections a SARM et de determiner l’incidence de ces infections dans un echantillon d’etablissements de soins representatifs des hopitaux publics francais.

European Journal of Clinical Microbiology & Infectious Diseases, Jul 24, 2015
The influence of hospital use of antibiotics other than cephalosporins and fluoroquinolones on ex... more The influence of hospital use of antibiotics other than cephalosporins and fluoroquinolones on extendedspectrum beta-lactamase (ESBL) resistance among Enterobacteriaceae is poorly known. Our objective was to explore the association between ESBL and hospital use of various classes of antibacterial agents. The relationship between monthly use of 19 classes of antibacterial agents and incidence of nosocomial ESBL-producing Enterobacteriaceae in a French hospital was studied between 2007 and 2013. Five antibiotic classes were significantly and independently associated with ESBL resistance. Uses of tetracyclines (link esti-mate±SE, 0.0066±0.0033), lincosamides (0.0093±0.0029), and other antibacterial agents (0.0050±0.0023) were associated with an increased incidence, while nitrofurantoin (−0.0188±0.0062) and ticarcillin and piperacillin with or without enzyme inhibitor (−0.0078±0.0031) were associated with a decreased incidence. In a multivariate model including 3rd-and 4th-generation cephalosporins, fluoroquinolones, amoxicillin, and amoxicillin-clavulanate, 3rd-and 4th-generation cephalosporins (0.0019 ± 0.0009) and fluoroquinolones (0.0020±0.0008) were associated with an increased ESBL resistance, whereas amoxicillin and amoxicillin-clavulanate were not. Hospital use of tetracyclines and lincosamides may promote ESBL resistance in Enterobacteriaceae. Nitrofurantoin and ticarcillin and piperacillin with or without enzyme inhibitor should be considered as potential alternatives to broad-spectrum cephalosporins and fluoroquinolones to control the diffusion of ESBL resistance.

Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, mos... more Diseases caused by arboviruses are on the increase worldwide. In addition to arthropod bites, most arboviruses can be transmitted via accessory routes. Products of human origin (labile blood products, solid organs, hematopoietic stem cells, tissues) present a risk of contamination for the recipient if the donation is made when the donor is viremic. This narrative review describes the risks of acquiring certain arboviral diseases from human products, mainly solid organs and hematopoietic stem cells, in the French context. Mainland France and its overseas territories are exposed to a complex array of imported and endemic arboviruses, which differ according to their respective location. The main risks considered in this study are infections by West Nile virus, dengue virus and tick-borne encephalitis virus. The ancillary risks represented by Usutu virus infection, chikungunya and Zika are also addressed more briefly. For each disease, the guidelines issued by the French High Council of...
International Journal of Research in Medical Science
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Papers by Didier Lepelletier