Dr COURJON Johan
Infectiologue
Praticien Hospitalier
Infectiologue référent du centre associé pour la prise en charge des IOA complexes
Secrétariat: Aminata SOW
Tél.: 04.92.03.83.53
Mail.: sow.a@chu-nice.fr
Titres & Diplômes
Titres universitaires
2021 Doctorat en Immunologie et Microbiologie, Université Côte d’Azur
2020 DU méthodologie en recherche clinique ISPED Université de Bordeaux
2017 DESC pathologie infectieuse et tropicale
2015 Diplôme de Docteur en médecine
2015 Diplôme d’Etudes Spécialisées en Médecine Interne
2013-2014 DIU Prévention et prise en charge des infections ostéo-articulaires (Faculté de médecine de Tours)
2013 Master 2 de Pathologie Humaine, Maladies Infectieuses Contagion Prévention (Université d’Aix-Marseille). Intitulé du mémoire :
« Inactivation de la GTPase RhoA par EDIN-B dans un modèle murin de pneumonie à Staphylococcus aureus ST80-MRSA-IV ». Stage effectué dans l’équipe d’Emmanuel Lemichez,
Centre Méditerranéen de Médecine Moléculaire UMR INSERM U1065/UNS.
2010 DU d’Antibiologie de la faculté de médecine de Nice
Titres hospitaliers
2016-2020 Chef de clinique des universités- assistant des hôpitaux dans le service d’Infectiologie du Pr P-M Roger
2015-2016 Assistant spécialiste dans le service d’Infectiologie du Pr P-M Roger
2008-2015 Internat
Titres scientifiques
2021 Soutenance de la thèse de science programmée le 31 mars 2021
2013 Master 2 de Pathologie Humaine, Maladies Infectieuses Contagion Prévention (Université d’Aix-Marseille). Intitulé du mémoire :
« Inactivation de la GTPase RhoA par EDIN-B dans un modèle murin de pneumonie à Staphylococcus aureus ST80-MRSA-IV ». Stage effectué dans l’équipe d’Emmanuel Lemichez,
Centre Méditerranéen de Médecine Moléculaire UMR INSERM U1065/UNS.
2006 Maitrise de Science biologiques et médicales Université Claude Bernard Lyon 1
Activités d’enseignement et de pédagogie
Implication dans l’UFR
- Commission pédagogique
- 2019-2020 :Commission de la réforme du 2ème cycle, participation à l’élaboration du nouveau programme du 2ème cycle (2 séminaires)
DFASM UE6
2019/2020 : 14 heures
2018/2019 : 9 heures
2017/2018 : 21 heures
2016/2017 : 21 heures
2015/2016 : 9 heures
DFASM hors UE6
- Conférences de préparation à l’ECN organisées par la faculté de médecine de Nice de 2011 à 2021 en infectiologie (2 séances par an)
- De 2013 à 2021 participation aux séances d’aide au raisonnement clinique (2 séances/bimestre, 1 heure par séance) données aux étudiants du service d’Infectiologie
- Participation au tutorat des externes en DCEM3 mis en place dans le service d’Infectiologie par le Dr Pulcini et le Dr Demonchy en 2010-2011, 2012-2013 et 2013-2014 (5 séances de 2 heures par an).
DU
- DU d’antibiologie de la faculté de médecine de Nice.
- Participation à l’organisation du DU en 2020-2021 avec le Pr Michel Carles
- Thématiques des cours donnés: « Pharmacocinétique clinique des antibiotiques : quand et comment doser les antibiotiques ? », « Infections ostéo-articulaires » et « Infections du pied diabétique », « Fluoroquinolones », « Macrolides », « Infections neuroméningées » 2021 en cours, 2019 6h00, 2017 5h30, 2015 2h00:
DIU
- DIU national Infections ostéo-articulaires / Session 2 : Atelier cas clinique : diagnostic différentiel d’une IOA prothétique
DES biologie médicale
- 1H : infections de VVC 2018
Capacités
- Enseignement de 2 heures pour une capacité de gérontologie au CHU de Nice en janvier 2016, décembre 2017 et décembre 2019 sur le thème : infections nosocomiales et iatrogénie
FMC
- Formation FAF-PM aux médecins généralistes sur COVID 19 en avril 2020 deux fois deux heures (fmc ActioN)
- Epidémiologie de la résistance bactérienne et choix de l’antibiothérapie probabiliste en orthopédie pour le réso Infectio PACA-Est 2019
- Daptomycine au cours des IOA pour le réso Infectio PACA-Est 2018
- DPC « Situations courantes et complexes en médecine générale » durant 3 heures pour une mise au point sur le bon usage des antibiotiques en 2017.
- Présentation de 20 minutes à la réunion du 4 juin 2016 de l’association régionale de médecine vasculaire PACA intitulée : « le pied diabétique : approche multidisciplinaire, le point de vue du médecin Infectiologue ».
Encadrement de thèses de médecine
- Comparaison pharmacologique des administrations continue et itérative de cloxacilline par voie intraveineuse au cours des infections ostéo-articulaires à Staphylococcus aureus. Publiée dans AAC
- Epidémiologie bactérienne des IOA survenant après fracture ouverte au CHU de Nice. Publiée sous forme de lettre à CMI
- Audit national des pratiques médicales et chirurgicales au cours des IOA complexes (en collaboration avec le Pr Tristan Ferry aux HCL). Publiée dans BMC Inf Dis
- Usage de la clindamycine pour le traitement des infections de prothéses d’épaule à Cutibacterium acnes. Poster RICAI 2019, soumis à Journal of shoulder and elbow surgery
IFSI / Ecole de sages-femmes (SF)
| IFSI | SF | |
| 2011/2012 | 4h | |
| 2012/2013 | ||
| 2013/2014 | 3h | 4h |
| 2014/2015 | 1h | |
| 2015/2016 | 5.5h | 3h |
| 2016/2017 | 6h | 3h |
| 2017/2018 | 10h | |
| 2018/2019 | 8h | |
| 2019/2020 | 9H30 | |
| 2020/2021 | 4h |
Activité de recherche
Appartenance à une équipe d‘accueil EPST (Inserm) labellisée par AERES/HCERES
Centre de médecine moléculaire, Nice, INSERM U1065, équipe 6 Virulence microbienne et signalisation inflammatoire, Dr Laurent Boyer
Encadrement d’étudiants
- Master 2 : 2020-2021 Eva Mellan, co-encadrement avec le Dr Laurent Boyer au sein de l’équipe 6 du C3M INSERM U1065 dans le cadre de la poursuite du projet NLRP3-BACT visant à évaluer le niveau d’activation de l’inflammasomes NLRP3 chez les patients bactériémiques à aureus et E. coli
Protocole en cours
- Projet PRO-Dalba : utilisation de la dalbavancine en première intention dans les infections de prothèse de genou ou de hanche à staphylocoque. AOI 15 000e+ Industrie (Correvio) 200 000e CHU de Nice + Tourcoing (Pr Senneville) + Ambroise Paré (Dr Dinh)
- Projet NLRP3-BACT : poursuite du projet transversal Inserm C3M-Infectiologie visant à évaluer le niveau d’activation de l’inflammasomes NLRP3 chez les patients bactériémiques à aureus et E. coli. AOI 15 000e + Co-financement 15 000e
- Projet COVID-19 CovInnate : évaluation du niveau d’activation de l’inflammasome NLRP3 chez les patients COVID-19, résultats publiés dans Blood advances, étude ancillaire sur l’utilité des tests d’activation de l’inflammasome NLRP3 pour distinguer les répondeurs et non-répondeurs à la corticothérapie.
Première partie du projet financée par l’Université Côte d’Azur 15 000e. Etude ancillaire soumise à l’ANR COVID-19 Resilience.
- Investigateur pour DISCOVERY
- Investigateur dans les PHRC
SHASAR
CLOCEBA
RIFAMAB
Activités dans les organismes de recherche
2021 : intégration du conseil scientifique du GIRCI Méditerranée (suppléant)
Activité de soins
Prise en charge des patients
- Infectiologue référent du centre associé pour la prise en charge des IOA complexes
-consultation dédiée (433 consultations sur 2018 et 2019)
-veille téléphonique (7/7) pour les avis émanant de l’IULS (plus de 150 avis/an)
-co-organisation de la RCP IOA complexes
- Période COVID-19 : Alternance unité COVID-19 14 lits, Soins intensifs COVID-19 (8 lits avec OHD) et Infectiologie conventionnelle 10 lits
- Coordonnateur recherche COVID-19 pour l’infectiologie : projets locaux, nationaux et européens
- Hors période COVID-19 : Hospitalisation conventionnelle en Infectiologie: 17 lits
3 visites par semaine, CV quotidiennes, ½ journée de consultation par semaine.
- Partenariat hospitalier avec l’hématologie pour la prise en charge des infections complexes de l’immunodéprimé
- De mai 2015 à mars 2017 participation au Recours Rapides (avis téléphoniques CHU et non-CHU + consultations d’urgences).
- Astreintes de sécurité du service pour PACA-Est
Responsabilités hospitalières
- Membre de la commission des anti-infectieux
- Groupe de travail risques NRC et REB: interlocuteur du service d’infectiologie pour la révision 2019 du document « dispositif de gestion de crise du CHU de Nice »
Service rendu à la spécialité
- Reviewing pour MMI à la demande du Pr Pierre-Marie Roger (co-éditeur) : 6 articles depuis 2017
Activité d’intérêt général
- Membre du groupe de recherche ESCMID pour les infections associées au matériel étranger (ESGIAI) depuis Mai 2017
- Membre de la SPILF depuis 2019
Score SIGAPS mars 2021 : 500
Travaux originaux (anglais)
Publications 2021 du Dr COURJON Johan
Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic
Thomas Hubiche, Nathalie Cardot-Leccia, Florence Le Duff, Barbara Seitz-Polski, Pascal Giordana, Christine Chiaverini, Valérie Giordanengo, Géraldine Gonfrier, Vincent Raimondi, Olivier Bausset, Zoubir Adjtoutah, Margaux Garnier, Fanny Burel-Vandenbos, Bérengère Dadone-Montaudié, Véréna Fassbender, Aurélia Palladini, Johan Courjon, Véronique Mondain, Julie Contenti, Jean Dellamonica, Georges Leftheriotis, Thierry Passeron
https://pubmed.ncbi.nlm.nih.gov/33237291/
Abstract
Importance: Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown.
Objective: To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic.
Design, setting, and participants: In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included.
Main outcomes and measures: Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis.
Results: Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19.
Conclusions and relevance: Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.
Trial registration: ClinicalTrials.gov Identifier: NCT04344119.
Escherichia coli Rho GTPase-activating toxin CNF1 mediates NLRP3 inflammasome activation via p21-activated kinases-1/2 during bacteraemia in mice
Océane Dufies, Anne Doye, Johan Courjon, Cédric Torre, Gregory Michel, Celine Loubatier, Arnaud Jacquel, Paul Chaintreuil, Alissa Majoor, Rodolphe R Guinamard, Alexandre Gallerand, Pedro H V Saavedra, Els Verhoeyen, Amaury Rey, Sandrine Marchetti, Raymond Ruimy, Dorota Czerucka, Mohamed Lamkanfi, Bénédicte F Py, Patrick Munro, Orane Visvikis, Laurent Boyer
https://pubmed.ncbi.nlm.nih.gov/33432150/
Abstract
Inflammasomes are signalling platforms that are assembled in response to infection or sterile inflammation by cytosolic pattern recognition receptors. The consequent inflammasome-triggered caspase-1 activation is critical for the host defence against pathogens. During infection, NLRP3, which is a pattern recognition receptor that is also known as cryopyrin, triggers the assembly of the inflammasome-activating caspase-1 through the recruitment of ASC and Nek7. The activation of the NLRP3 inflammasome is tightly controlled both transcriptionally and post-translationally. Despite the importance of the NLRP3 inflammasome regulation in autoinflammatory and infectious diseases, little is known about the mechanism controlling the activation of NLRP3 and the upstream signalling that regulates the NLRP3 inflammasome assembly. We have previously shown that the Rho-GTPase-activating toxin from Escherichia coli cytotoxic necrotizing factor-1 (CNF1) activates caspase-1, but the upstream mechanism is unclear. Here, we provide evidence of the role of the NLRP3 inflammasome in sensing the activity of bacterial toxins and virulence factors that activate host Rho GTPases. We demonstrate that this activation relies on the monitoring of the toxin’s activity on the Rho GTPase Rac2. We also show that the NLRP3 inflammasome is activated by a signalling cascade that involves the p21-activated kinases 1 and 2 (Pak1/2) and the Pak1-mediated phosphorylation of Thr 659 of NLRP3, which is necessary for the NLRP3-Nek7 interaction, inflammasome activation and IL-1β cytokine maturation. Furthermore, inhibition of the Pak-NLRP3 axis decreases the bacterial clearance of CNF1-expressing UTI89 E. coli during bacteraemia in mice. Taken together, our results establish that Pak1 and Pak2 are critical regulators of the NLRP3 inflammasome and reveal the role of the Pak-NLRP3 signalling axis in vivo during bacteraemia in mice.
Functional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients
Functional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients
Caroline Ruetsch, Vesna Brglez, Marion Crémoni, Kévin Zorzi, Céline Fernandez, Sonia Boyer-Suavet, Sylvia Benzaken, Elisa Demonchy, Karine Risso, Johan Courjon, Eric Cua, Carole Ichai, Jean Dellamonica, Thierry Passeron, Barbara Seitz-Polski
https://pubmed.ncbi.nlm.nih.gov/33585507/
Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan in December 2019 and has since spread across the world. Even though the majority of patients remain completely asymptomatic, some develop severe systemic complications. In this prospective study we compared the immunological profile of 101 COVID-19 patients with either mild, moderate or severe form of the disease according to the WHO classification, as well as of 50 healthy subjects, in order to identify functional immune factors independently associated with severe forms of COVID-19. Plasma cytokine levels, and cytokine levels upon in vitro non-specific stimulation of innate and adaptive immune cells, were measured at several time points during the course of the disease. As described previously, inflammatory cytokines IL1β, IL6, IL8, and TNFα associated with cytokine storm were significantly increased in the plasma of moderate and severe COVID-19 patients (p < 0.0001 for all cytokines). During follow-up, plasma IL6 levels decreased between the moment of admission to the hospital and at the last observation carried forward for patients with favorable outcome (p = 0.02148). After in vitro stimulation of immune cells from COVID-19 patients, reduced levels of both type I and type II interferons (IFNs) upon in vitro stimulation were correlated with increased disease severity [type I IFN (IFNα): p > 0.0001 mild vs. moderate and severe; type II IFN (IFNγ): p = 0.0002 mild vs. moderate and p < 0.0001 mild vs. severe] suggesting a functional exhaustion of IFNs production. Stimulated IFNα levels lower than 2.1 pg/ml and IFNγ levels lower than 15 IU/mL at admission to the hospital were associated with more complications during hospitalization (p = 0.0098 and p =0.0002, respectively). A low IFNγ level was also confirmed by multivariable analysis [p = 0.0349 OR = 0.98 (0.962; 0.999)] as an independent factor of complications. In vitro treatment with type IFNα restored type IFNγ secretion in COVID-19 patients while the secretion of pro-inflammatory cytokines IL6 and IL1β remained stable or decreased, respectively. These results (a) demonstrate a functional exhaustion of both innate and adaptive immune response in severe forms of COVID-19; (b) identify IFNα and IFNγ as new potential biomarkers of severity; and (c) highlight the importance of targeting IFNs when considering COVID-19 treatment in order to re-establish a normal balance between inflammatory and Th1 effector cytokines.
Keywords: COVID-19; immunology; infectious diseases; interferon; personalized medicine.
Copyright © 2021 Ruetsch, Brglez, Crémoni, Zorzi, Fernandez, Boyer-Suavet, Benzaken, Demonchy, Risso, Courjon, Cua, Ichai, Dellamonica, Passeron and Seitz-Polski.
Heterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity
Johan Courjon, Océane Dufies, Alexandre Robert, Laurent Bailly, Cédric Torre, David Chirio, Julie Contenti, Sébastien Vitale, Céline Loubatier, Anne Doye, Christelle Pomares-Estran, Géraldine Gonfrier, Romain Lotte, Patrick Munro 1, Orane Visvikis, Jean Dellamonica, Valérie Giordanengo, Michel Carles, Laurent Yvan-Charvet, Stoyan Ivanov, Patrick Auberger, Arnaud Jacquel, Laurent Boyer
https://pubmed.ncbi.nlm.nih.gov/33683342/
Abstract
Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.
© 2021 by The American Society of Hematology.
Management of prosthetic joint infections in France: a national audit to identify key situations requiring innovation and homogenization
Marion Le Maréchal, Zoé Cavalli, Cécile Batailler, Jean-François Gonzalez, André Ferreira, Sébastien Lustig, Tristan Ferry, Johan Courjon
https://pubmed.ncbi.nlm.nih.gov/33933020/
Abstract
Background: Prosthetic joint infections (PJI) are one of the most serious complication of arthroplasty. The management of PJI needs a multidisciplinary collaboration between orthopaedic surgeon, infectious disease specialist and microbiologist. In France, the management of PJI is organized around reference centres (CRIOACs). Our main objective was to perform an audit through a questionnaire survey based on clinical cases, to evaluate how French physicians manage PJI. Eligible participants were all physicians involved in care of patients presenting a PJI. Physicians could answer individually, or collectively during a multidisciplinary team meeting dedicated to PJI. The survey consisted as three questionnaires organized in a total of six clinical cases.
Results: Answers from the CRIOACs to the three questionnaires were 92, 77, and 53%. Between 32 and 39% of respondents did not administer antibiotic prophylaxis despite positive S. aureus pre-operative documentation. One-stage exchange strategy was widely preferred in all clinical cases, with no difference between CRIOACs and other centres. Rifampicin was prescribed for S. aureus PJI, in a situation with (90-92%) or without any prosthesis (70%). There was no consensus for the total antibiotic regimen duration, with prescriptions from six to 12 weeks for a majority of respondents.
Conclusions: Surgical strategy for the management of PJI was homogenous with a preference for a one-stage exchange strategy. Medical management was more heterogenous, which reflects the heterogeneity of those infections and difficulties to perform studies with strong conclusions.
Keywords: Arthritis infection; Clinical audit; Joint prosthesis; Rifampin; Staphylococcus aureus; Surveys and questionnaires.
Proteinuria as a Biomarker for COVID-19 Severity
Proteinuria as a Biomarker for COVID-19 Severity
Hajar Ouahmi, Johan Courjon, Lucas Morand, Juliette François, Vincent Bruckert, Romain Lombardi, Vincent Esnault, Barbara Seitz-Polski, Elisa Demonchy, Jean Dellamonica, Sonia Boyer-Suavet
https://pubmed.ncbi.nlm.nih.gov/33767630/
Abstract
Background: Renal involvement in syndrome coronavirus 2 (SARS-CoV-2) infection has been retrospectively described, especially acute kidney injury (AKI). However, quantitative proteinuria assessment and its implication in coronavirus disease 2019 (COVID-19) remain unknown.
Methods: In this prospective, multicenter study in France, we collected clinical and biological data including urinary protein to creatine ratio (UPCR) in patients presenting with moderate to severe COVID-19. Clinical outcome was analyzed according to the level of UPCR.
Results: 42/45 patients (93.3%) had renal involvement (abnormal urinary sediment and/or AKI). Significant proteinuria occurred in 60% of patients. Urine protein electrophoresis showed tubular protein excretion in 83.8% of patients with proteinuria. Inflammatory parametersand D-dimer concentrations correlated with proteinuria level. Patients who required intensive care unit (ICU) admission had higher proteinuria (p = 0.008). On multivariate analysis, proteinuria greater than 0.3 g/g was related to a higher prevalence of ICU admission [OR = 4.72, IC95 (1.16-23.21), p = 0.03], acute respiratory distress syndrome (ARDS) [OR = 6.89, IC95 (1.41-53.01, p = 0.02)], nosocomial infections [OR = 3.75, IC95 (1.11-13.55), p = 0.03], longer inpatient hospital stay (p = 0.003).
Conclusion: Renal involvement is common in moderate to severe SARS-CoV-2 infection. Proteinuria at baseline is an independent risk factor for increased hospitalization duration and ICU admission in patients with COVID-19.
Keywords: COVID-19; SARS-CoV-2; acute kidney injury; biomarker; kidney involvement; pronostic and predictive factors; proteinuria.
Copyright © 2021 Ouahmi, Courjon, Morand, François, Bruckert, Lombardi, Esnault, Seitz-Polski, Demonchy, Dellamonica and Boyer-Suavet.
Publications 2020 du Dr COURJON Johan
A Population Pharmacokinetic Analysis of Continuous Infusion of Cloxacillin during Staphylococcus aureus Bone and Joint Infections
Johan Courjon, Margaux Garzaro, Pierre-Marie Roger, Raymond Ruimy, Thibaud Lavrut, Mikaël Chelli, Jean-Luc Raynier, David Chirio, Elisa Demonchy, Laura Cabane, François Jehl, Christophe Trojani, Antoine Grillon, Sylvain Goutelle
https://pubmed.ncbi.nlm.nih.gov/32988822/
Abstract
Intravenous administration of antibiotics is recommended during the early phase of methicillin-susceptible S. aureus (MSSA) bone and joint infection (BJI). We sought to compare the plasma concentrations of cloxacillin administered alternately by continuous and intermittent infusion (CI and ItI) in patients with MSSA BJI. In this prospective crossover trial, patients were randomly assigned to receive either 3 days of CI (two 75-mg/kg 12-h cloxacillin infusions per day) and then 3 days of ItI (four 37.5-mg/kg 1-h cloxacillin infusions per day) or vice versa. The drug concentration measurement was performed on day 3 of each type of administration at 1, 6, and 11 h and at 1, 2, 3, 4, and 6 h after the beginning of CI and ItI, respectively. We used the nonparametric algorithm NPAG to estimate population pharmacokinetic (PK) parameters. The final model was used to perform pharmacokinetic/pharmacodynamic (PK/PD) simulations and calculate the probabilities of target attainment (PTA) for several ItI and CI dosing regimens. We considered two PK/PD targets of time spent above the MIC for free cloxacillin concentrations (fT>MIC): 50 and 100%. Eighty-four concentrations from 11 patients were analyzed. A two-compartment model adequately described the data. ItI with q6h regimens and short 1-h infusions of 2,000 or 3,000 mg were associated with low PTA, even for the low target (50% fT>MIC) while 3-h infusions and continuous infusions (6 to 12 g/day) were associated with a PTA of >90% for an MIC up to 0.5 mg/liter. These results support the use of prolonged or continuous infusion of cloxacillin in patients with BJI.
Keywords: Staphylococcus aureus; antibiotics; bone and joint infections; cloxacillin; continuous infusion; osteomyelitis; penicillin; pharmacodynamic; pharmacokinetics; population PK analysis; population pharmacokinetics.
Copyright © 2020 American Society for Microbiology.
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
Philippe Gautret, Jean-Christophe Lagier, Philippe Parola, Van Thuan Hoang, Line Meddeb, Morgane Mailhe, Barbara Doudier, Johan Courjon, Valérie Giordanengo, Vera Esteves Vieira, Hervé Tissot Dupont, Stéphane Honoré, Philippe Colson, Eric Chabrière, Bernard La Scola, Jean-Marc Rolain, Philippe Brouqui, Didier Raoult
https://pubmed.ncbi.nlm.nih.gov/32205204/
Abstract
Background: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads.
Patients and methods: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.
Results: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
Conclusion: Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
Keywords: 2019-nCoV; Azithromycin; COVID-19; Clinical trial; Hydroxychloroquine; SARS-CoV-2.
Copyright © 2020. Published by Elsevier B.V.
QT Interval Prolongation Under Hydroxychloroquine/Azithromycin Association for Inpatients With SARS-CoV-2 Lower Respiratory Tract Infection
Sok-Sithikun Bun, Philippe Taghji, Johan Courjon, Fabien Squara, Didier Scarlatti, Guillaume Theodore, Delphine Baudouy, Benjamin Sartre, Mohamed Labbaoui, Jean Dellamonica, Denis Doyen, Charles-Hugo Marquette, Jacques Levraut, Vincent Esnault, Sok-Siya Bun, Emile Ferrari
https://pubmed.ncbi.nlm.nih.gov/32588427/
Abstract
Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia’s correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24th to April 20th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.
© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
Publications 2019 du Dr COURJON Johan
Adherence to antibiotic guidelines for erysipelas or cellulitis is associated with a favorable outcome
Camille Klotz, Johan Courjon, Céline Michelangeli, Elisa Demonchy, Raymond Ruimy, Pierre-Marie Roger
https://pubmed.ncbi.nlm.nih.gov/30685804/
Abstract
Outside areas of S. aureus strains resistant to methicillin (MRSA) in the community, no studies showed a relationship between the treatment for erysipelas or cellulitis and the outcome. We aimed to measure the impact of an internal therapeutic protocol, based on national guidelines on patients’ outcome. This study was based on the dashboard of the infectious diseases department, which prospectively includes 28 parameters for all admitted patients. We included community-acquired erysipelas and cellulitis; exclusion criteria were abscesses at admission; ear, nose, throat, or dental cellulitis; pyomyositis; and length of stay ≤ 2 days. Adherence to guidelines was defined by the use of amoxicillin, amoxicillin/clavulanic acid, clindamycin, or pristinamycin, alone or in combination or successively. A poor outcome was defined by surgical procedure or intensive care requirement or death occurring after 5 days or more of antibiotic therapy. From July 2005 to June 2017, 630 cases of erysipelas or cellulitis were included. Blood cultures performed in 567 patients (90%) were positive in 39 cases (6.9%). Adherence rate to guidelines was 65% (410 cases). A poor outcome was recorded in 54 (8.5%) patients, less frequently in case of adherence to guidelines: 26/410 (6.3%) vs 28/220 (12.7%), p = 0.007. In logistic regression analysis, two risk factors were associated with a poor outcome: peripheral arterial disease, AOR 4.80 (2.20-10.49); and bacteremia, AOR 5.21 (2.31-11.76), while guideline adherence was the only modifiable protective factor, OR 0.48 (0.26-0.89). In erysipelas and cellulitis, adherence to guidelines was associated with a favorable outcome.
Keywords: Antibiotic therapy; Cellulitis; Erysipelas; Guidelines; Outcome; SSTI.
Amoxicillin/clavulanic acid+aminoglycoside as empirical antibiotic treatment in severe community-acquired infections with diagnostic uncertainty
Johan Courjon, David Chirio, Elisa Demonchy, Céline Michelangeli, Nicolas Degand, Pierre-Marie Roger
https://pubmed.ncbi.nlm.nih.gov/30707379/
Abstract
Diagnostic uncertainty is common in the emergency room and multidrug-resistant bacteria emerge in the community setting, implying to establish the most efficient empirical antibiotic therapy (eEAT). Our aim was to identify such eEAT, considering that in case of DU with severe clinical presentation, most prescribers would propose an empiric combination (EC). The medical dashboard of our ward records prospectively 28 characteristics of each hospitalization including hospitalization motive, final diagnosis, and all antibiotics prescribed. All patients with community-acquired bacteremia (CAB) were included. DU was defined by a discrepancy between suspected diagnosis in the emergency room and final diagnosis. eEAT was defined by in vitro activity of at least one prescribed compound. Finally, independently from the dashboard, we retrospectively compared 2 CTs: amoxicillin/clavulanic acid (AMC)+gentamicin (G) and cefotaxime (3GC)+G. One thousand thirty-four patients with a final diagnosis of CAB were identified from July 2005 to June 2018, including 357 DU (35%) at baseline. eEAT (n = 553) was associated with a trend towards a lower death rate compared to inefficient therapies: 5.4 vs 10.0% (p = 0.053), and effective antibiotic reassessment was the most protective factor against an unfavorable outcome: 0.34 (0.16-0.71). Bacteria involved in case of UD were resistant to AMC+G and to 3GC+G in 8.1% and 12.8% of patients, respectively. Diagnostic uncertainty was a frequent event requiring antibiotic reassessment. As the latter was not systematically realized, the best eEAT is required and AMC+aminoglycoside should be considered.
Keywords: Bacteremia; Community-acquired infection; ESBL Enterobacteriaceae; Empirical antibiotic therapy; Outcome.
French national cohort of first use of dalbavancin: A high proportion of off-label use
French national cohort of first use of dalbavancin: A high proportion of off-label use
Aurélien Dinh, Clara Duran, Patricia Pavese, Lydie Khatchatourian, Boris Monnin, Alexandre Bleibtreu, Eric Denis, Cédric Etienne, Nicolas Rouanes, Rafael Mahieu, Frédérique Bouchand, Benjamin Davido, Romain Lotte, Philippe Cabaret, Fabrice Camou, Pascal Chavanet, Assi Assi, Silvia Limonta, Catherine Lechiche, Raphaëlle Riou, Johan Courjon, Gabriela Illes, Flore Lacassin-Beller, Eric Senneville; Dalbavancin French Study Group
https://pubmed.ncbi.nlm.nih.gov/31400471/
Abstract
Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient’s last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective.
Keywords: Bone and joint infection; Dalbavancin; Endocarditis; Off-label; Staphylococci.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Infectious disease symptoms and microbial carriage among French medical students travelling abroad: A prospective study
Thi Loi Dao, Van Thuan Hoang, Tran Duc Anh Ly, Amal Magmoun, Naomie Canard, Tassadit Drali, Florence Fenollar, Laetitia Ninove, Didier Raoult, Philippe Parola, Johan Courjon, Philippe Gautret
https://pubmed.ncbi.nlm.nih.gov/31870880/
Abstract
Background: In France, no previous studies have focused specifically on health problems among medical students during internships abroad including the clinical symptoms suggestive of infectious diseases and the acquisition of pathogen carriage.
Methods: Clinical follow up and qPCR based respiratory, gastrointestinal and vaginal pathogen carriage before and after travel were prospectively assessed in a cohort of medical students departing from Marseille, France.
Results: 134 students were included. 73.9%, 38.8% and 5.0% of students reported gastrointestinal, respiratory and vaginal symptoms, respectively. The acquisition rate of Enteroaggregative Escherichia coli (EAEC) and Enteropathogenic E. coli (EPEC) was 53% and 41%, respectively. The acquisition of respiratory viruses was low but associated with persisting symptoms, while bacterial acquisition ranged from 3.3% for Streptococcus pyogenes to 15.0% for Haemophilus influenzae. Gardnerella vaginalis and Atopobium vaginae acquisition rates were 7.7% and 14.3% respectively. Five students (5.1%) had molecular quantification criteria for bacterial vaginosis on return.
Conclusion: This preliminary study demonstrates that besides the known risk of gastrointestinal and respiratory infections and associated changes in intestinal and respiratory microbiota, medical students abroad may also experience changes in vaginal microbiota leading, in some cases, to clinical symptoms or the acquisition of bacterial vaginosis, which may be asymptomatic.
Keywords: Bacterial vaginosis; Gastrointestinal infection; Medical students; Microbial carriage; Respiratory infection; Travellers.
Copyright © 2019 Elsevier Ltd. All rights reserved.
Publications 2018 du Dr COURJON Johan
A toolkit for the management of infection or colonization by extended-spectrum beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome of a European project
V Mondain, G Secondo, R Guttmann, G Ferrea, A Dusi, M Giacomini, J Courjon, C Pradier
https://pubmed.ncbi.nlm.nih.gov/29600324/
Abstract
Among European countries, prevalence rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering the Mediterranean. This is the case for Italy, with 26% of Escherichia coli displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E toolkit designed to assist clinicians in managing patients harboring ESBL-E was favorably implemented in Southern France. In a context of lack of specific Italian recommendations, its extension to an adjacent region of Italy was made possible through a cross-border EU cooperation program. Italian infectious disease (ID) specialists, microbiologists, and community-based general practitioners from three districts in Liguria were offered a toolkit consisting in a warning system and detailed procedures for the management of patients harboring ESBL-E, including seeking advice from an ID specialist, and were trained during 52 video conferences by an experienced French team. Indications and trends in antimicrobial prescription were studied following implementation of the toolkit. Between November 2013 and November 2014, 476 patients were identified as harboring ESBL-E and expert advice was sought for 364 of these; all patients and/or their caregivers were advised on appropriate hygiene measures and 209/341 with documented management received antimicrobial treatment, while asymptomatic carriers (39%) were not prescribed antibiotics. The ESBL-E toolkit was well received by the healthcare staff. A specific, simple tool consisting in a care-bundle approach to manage ESBL-E carriers can restrict antimicrobial prescription to symptomatic patients while raising awareness among caregivers of the importance of seeking expert advice and implementing appropriate hygiene measures.
Cefoxitin-based antibiotic therapy for extended-spectrum β-lactamase-producing Enterobacteriaceae prostatitis: a prospective pilot study
Elisa Demonchy, Johan Courjon, Estelle Ughetto, Matthieu Durand, Karine Risso, Rodolphe Garraffo, Pierre-Marie Roger
https://pubmed.ncbi.nlm.nih.gov/29378342/
Abstract
The emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis.
Keywords: Acute bacterial prostatitis; Carbapenem-sparing regimen; Cefoxitin; Chronic bacterial prostatitis; ESBL-producing Enterobacteriaceae; Prostatitis.
Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
Fast track consultation in the infectious diseases department of a French university hospital: evaluation of the service delivered to the general practitioner
Nicolas Weiss, Johan Courjon, Christian Pradier, Cécile Caisso, Véronique Mondain, Pierre-Marie Roger, Elisa Demonchy
https://pubmed.ncbi.nlm.nih.gov/28829214/
Abstract
Purpose: Since 2010, the Infectious Diseases (ID) department of the Nice university hospital (France) has implemented a fast track consultation (FTC): it allows General Practitioners (GP) to directly reach an ID specialist through a dedicated phone number for initial advice. Depending on the first observation, a formal consultation can be planned within 48 h. Our aim was to evaluate in a pilot study, the contribution of the FTC regarding the management of patients 28 days after the first phone contact.
Methods: This prospective current care study was conducted between November 2014 and January 2015 in our ID department. The GP indicates the most likely diagnosis, the therapeutic strategy and the patient’s management he would have applied. After the formal consultation, ID specialist provides his diagnosis, therapeutic strategy and patient’s management. An adjudicative committee has evaluated the benefit of the FTC after 28 days of follow-up.
Results: Fifty-one patients referred by 49 GP were included. ID specialists modified the diagnosis in 22 (43%) patients, antibiotic treatment in 35 (68%) and treatment plan in 30 patients (59%). FTC provided at least one service for 41/51 patients (94%): antibiotic treatment was reassessed for 11 (22%) patients, averted for 9 (18%) patients, unnecessary hospitalization was avoided for 8 (16%) of them and emergency room visit averted for 5 (10%) patients.
Conclusions: FTC can provide significant improvement in the management of the patients in terms of decrease in unnecessary hospitalization, emergency room visit averted and appropriate use of antibiotics.
Keywords: Infectious disease advice; ambulatory medicine; appropriate antibiotherapy; fast track consultation; general practitioner; outpatients.
Managing ESBL-producing Enterobacteriaceae-related urinary tract infection in primary care: a tool kit for general practitioners
Aurélie Zucconi, Johan Courjon, Christophe Maruéjouls, Fabrice Saintpère, Nicolas Degand, Lilli Pandiani, Christian Pradier, Véronique Mondain
https://pubmed.ncbi.nlm.nih.gov/29594799/
Abstract
In Southern France, approximately 4% of E. coli isolates from community-acquired urinary tract infections are extended spectrum beta-lactamase producers, while carriage rates for enterobacteriaceae (ESBL-E) range from 3 to 6%. General practitioners (GP) are unfamiliar with the management of patients harboring ESBL-E. Providing them with a specific tool kit should assist in their therapeutic approach and optimize antimicrobial prescription an ESBL-E tool kit was developed by a multidisciplinary team: infectious diseases (ID) specialists, microbiologists, pharmacologists, and nursing home staff. This tool kit includes treatment protocols, GP and patient information leaflets, a list of infection control measures, and contact details of ID physicians for specialized advice. A community-based (including nursing homes) prospective study was conducted in 2012 in Southeastern France to test the tool kit in the context of ESBL-E-related urinary tract infections (UTI). ESBL-E-related UTI were identified in 88 patients, 66 GPs were contacted by the microbiology laboratory, 56 stated they were offered the tool kit, 48 said they had received it, and 41 stated they had read its contents. Use of the tool kit was significantly correlated with appropriate antibiotic prescription, which concerned 36/39 tool kit users versus 13/20 non-users (p = 0.0125) and 40 GPs expressed an average satisfaction rate of 4.2 on a scale of 0 to 5. Availability of a specific tool for managing patients harboring ESBL-E, now completed with a website, can assist community-based GPs and improve antimicrobial prescription.
Publications 2017 du Dr COURJON Johan
Efficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort study
Efficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort study
J Courjon, E Demonchy, E Cua, E Bernard, P-M Roger
https://pubmed.ncbi.nlm.nih.gov/28884303/
Abstract
Clindamycin has high bioavailability together with good diffusion in bone tissue and could represent an alternative antibiotic compound for the treatment of bone and joint infections (BJIs). However, data regarding the efficacy and safety of clindamycin for BJIs are limited. A monocentric cohort study based on our medical dashboard, which prospectively recorded 28 characteristics for all hospitalized patients since July 2005, was performed. BJIs were selected, and then, all mono-microbial BJI managed with clindamycin-based therapy were included. Remission was defined as the absence of clinical and/or microbiological relapse after treatment. The duration of follow-up without relapse was determined retrospectively using computerized medical records. For 10 years, 196 BJIs, of which 80 (41%) were device-associated infections, were treated with clindamycin-based therapy. The bacterial causative agent was Staphylococcus aureus in 130 cases (66%), coagulase-negative staphylococci in 29 cases (15%), streptococci in 31 cases (16%) and other bacteria in 6 cases (3%). When used in combination therapy, clindamycin was mainly paired with fluoroquinolones (31%) or rifampin (27%). The mean duration of clindamycin treatment was 7.4 ± 3.2 weeks (range, 1-24). An AE was recorded for 9 (4.5%) patients. Remission was recorded for 111 (57%) patients, with a mean duration of clinical follow-up of 28 ± 24 months. Treatment failure occurred in 22 (11%) patients, 50 patients (25%) were lost to follow-up, and 8 (4%) required long-term suppressive therapy. Among the assessable patients, clindamycin-based therapy was efficient in 111/133 cases (83%) and thus represents a reliable and safe alternative treatment option.
Keywords: Bone and joint infections; Clindamycin; Efficacy; Staphylococcus; Streptococcus; Tolerance.
Patients with community-acquired bacteremia of unknown origin: clinical characteristics and usefulness of microbiological results for therapeutic issues: a single-center cohort study
Johan Courjon, Elisa Demonchy, Nicolas Degand, Karine Risso, Raymond Ruimy, Pierre-Marie Roger
https://pubmed.ncbi.nlm.nih.gov/28526094/
Abstract
Bacteremia of unknown origin (BUO) are associated with increased mortality compared to those with identified sources. Microbiological data of those patients could help to characterize an appropriate empirical antibiotic treatment before bloodcultures results are available during sepsis of unknown origin. Based on the dashboard of our ward that prospectively records several parameters from each hospitalization, we report 101 community-acquired BUO selected among 1989 bacteremic patients from July 2005 to April 2016, BUO being defined by the absence of clinical and paraclinical infectious focus and no other microbiological samples retrieving the bacteria isolated from blood cultures. The in-hospital mortality rate was 9%. We retrospectively tested two antibiotic associations: amoxicillin-clavulanic acid + gentamicin (AMC/GM) and 3rd generation cephalosporin + gentamicin (3GC/GM) considered as active if the causative bacteria was susceptible to at least one of the two drugs. The mean age was 71 years with 67% of male, 31 (31%) were immunocompromised and 52 (51%) had severe sepsis. Eleven patients had polymicrobial infections. The leading bacterial species involved were Escherichia coli 25/115 (22%), group D Streptococci 12/115 (10%), viridans Streptococci 12/115 (10%) and Staphylococcus aureus 11/115 (9%). AMC/GM displayed a higher rate of effectiveness compared to 3GC/GM: 100/101 (99%) vs 94/101 (93%) (p = 0.04): one Enterococcus faecium strain impaired the first association, Bacteroides spp. and Enterococcus spp. the second. In case of community-acquired sepsis of unknown origin, AMC + GM should be considered.
Keywords: Antimicrobial resistance; Bacteremia; Bacteremia of unknown origin; Empirical antibiotic treatment; Primary bacteremia; Severe sepsis.
Pyogenic vertebral osteomyelitis of the elderly: Characteristics and outcomes
Pyogenic vertebral osteomyelitis of the elderly: Characteristics and outcomes
Johan Courjon, Adrien Lemaignen, Idir Ghout, Audrey Therby, Nadia Belmatoug, Aurélien Dinh, Guillaume Gras, Louis Bernard, DTS (Duration of Treatment for Spondylodiscitis) study group
https://pubmed.ncbi.nlm.nih.gov/29206837/
Abstract
Background: The incidence of pyogenic vertebral osteomyelitis (PVO) has increased over the past two decades. One possible cause of this increase is the aging of the population, which results in more comorbidities in high income countries.
Objective: To better characterize the clinical presentation and outcome of PVO in the elderly.
Design: We conducted a post-hoc analysis of a previously published trial that studied treatment duration in PVO and compared the presentation and outcomes according to age.
Participants: Our analysis included 351 patients among whom 85 (24%) were 75-years-old or more.
Results: There were no significant differences in the socio-demographics of the patients. Neoplasia and chronic inflammatory diseases were more common in the older group: 34% vs. 19% (p = 0.021) and 9% versus 1% (p = 0.004), respectively. There were no significant differences in clinical and radiological presentations between the groups in terms of back pain (337/351, 97%), fever (182/351, 52%), PVO localization, neurological signs and epidural abscess. Associated infective endocarditis (IE) was more frequent in the older group (37% vs. 14%, p<0.001). Streptococci were more frequently involved in infections of older patients (29% vs. 14%, p = 0.003) in contrast to Staphylococcus aureus (31% vs. 45%, p = 0.03). Older patients displayed higher mortality rates at 1 year (21% vs. 3%, p<0.001) and more adverse events related to cardiorespiratory failure (10.6% vs. 3.8%, p = 0.025), but had similar quality of life among the survivors.
Conclusion: During PVO, the clinical and radiological findings are similar in older patients. Global mortality rates are higher in older patients compared to younger patients, which could be explained by the increased frequency of neoplasia at diagnosis and higher prevalence of associated IE in the elderly.
Publications 2015 du Dr COURJON Johan
Clinical Aspects of Syphilis Reinfection in HIV-Infected Patients
Clinical Aspects of Syphilis Reinfection in HIV-Infected Patients
Johan Courjon, Thomas Hubiche, Nicolas Dupin, Philippe Alain Grange, Pascal Del Giudice
https://pubmed.ncbi.nlm.nih.gov/25823442/
Abstract
Background: The incidence of HIV-syphilis co-infection has risen since 2000, especially among men having sex with men (MSM). Syphilis reinfection can occur, but the clinical features of such events remain poorly characterized.
Objective: To compare the cutaneous lesions seen with syphilis reinfections with those of first episodes in HIV-infected patients.
Methods: In a cohort of HIV-infected patients, syphilis reinfection was established both clinically and biologically by evaluating changes in Venereal Disease Research Laboratory titers. Photographs and medical records were studied in order to determine the type of skin lesions and their quantification.
Results: Among 533 HIV-infected patients, 42 (8%) experienced a first syphilis infection. Thirteen episodes of reinfection occurred in 12/42 (28%) patients, all MSM. In 78% of cases, reinfections were less symptomatic than first episodes. All patients presented classical syphilis lesions.
Conclusions: We observed a high rate of reinfection, but with less severe skin manifestations during reinfection episodes.
EDIN-B Promotes the Translocation of Staphylococcus aureus to the Bloodstream in the Course of Pneumonia
Johan Courjon, Patrick Munro, Yvonne Benito, Orane Visvikis, Coralie Bouchiat, Laurent Boyer, Anne Doye, Hubert Lepidi, Eric Ghigo, Jean-Philippe Lavigne, François Vandenesch, Emmanuel Lemichez
https://pubmed.ncbi.nlm.nih.gov/26501320/
Abstract
It is crucial to define risk factors that contribute to host invasion by Staphylococcus aureus. Here, we demonstrate that the chromosomally encoded EDIN-B isoform from S. aureus contributes to the onset of bacteremia during the course of pneumonia. Deletion of edinB in a European lineage community-acquired methicillin resistant S. aureus (CA-MRSA) strain (ST80-MRSA-IV) dramatically decreased the frequency and magnitude of bacteremia in mice suffering from pneumonia. This deletion had no effect on the bacterial burden in both blood circulation and lung tissues. Re-expression of wild-type EDIN-B, unlike the catalytically inactive mutant EDIN-R185E, restored the invasive characteristics of ST80-MRSA-IV.
Keywords: bacteremia; methicillin-resistant Staphylococcus aureus; toxins; virulence factor.
Publications 2013 du Dr COURJON Johan
Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study
J Courjon, C Pulcini, E Cua, K Risso, F Guillouet, E Bernard, P-M Roger
https://pubmed.ncbi.nlm.nih.gov/23877571/
Abstract
Antibiotics are a significant cause of adverse events (AE), but few studies have focused on prescriptions in hospitalized patients. In infectious diseases departments, the high frequency and diversity of antibiotics prescribed makes AE post-marketing monitoring easier. The aim of our study was to assess the incidence and type of AE in the infectious diseases department of a French teaching tertiary-care hospital. The main characteristics of each hospitalization, including all antibiotics prescribed and any significant AE were recorded prospectively in the medical dashboard of the department. We included all patients having suffered an AE due to systemic antibiotics between January 2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68%) received an antibiotic and 151/2682 (5.6%) suffered an AE. Fifty-two (34%) AE were gastrointestinal disorders, 32 (21%) dermatological, 20 (13%) hepatobiliary, 16 (11%) renal and urinary disorders, 13 (9%) neurological and 11 (7%) blood disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and 38% were continued (including 11% with a dose modification). Patients suffering from AE had an increased length of stay (18 vs 10 days, P < 0.001). Our data could help choosing the safest antibiotic when several options are possible.
Skin findings of Staphylococcus aureus toxin-mediated infection in relation to toxin encoding genes
Skin findings of Staphylococcus aureus toxin-mediated infection in relation to toxin encoding genes
Johan Courjon, Thomas Hubiche, Alice Phan, Anne Tristan, Michele Bès, François Vandenesch, Jerome Etienne, Pascal Del Giudice, Yves Gillet
https://pubmed.ncbi.nlm.nih.gov/23446443/
Abstract
Background: Staphylococcal scalded skin syndrome and toxic shock syndrome are associated with exfoliatins and superantigens, respectively; and are easy to distinguish in their usual presentation. However, there is confusion about the mild forms of these 2 staphylococcal diseases. These mild forms are both designated as « staphylococcal scarlet fever » despite differences in their pathophysiology and clinical presentation. Our study aimed to distinguish between the clinical characteristics of the rash associated with exfoliatins and the rash associated with superantigens.
Methods: Patients were selected from the French National Reference Center for Staphylococci. We retrospectively compared the clinical characteristics of patients with a generalized rash during Staphylococcus aureus infection. Patients who met the criteria of staphylococcal scalded skin syndrome or toxic shock syndrome were excluded. The patients were classified into 2 groups depending on the presence of a gene coding for exfoliatin or for superantigenic toxin.
Results: We included 13 cases with exfoliatin and 9 with superantigens. The patients of the exfoliatin group were more likely to have facial involvement, fold involvement and a superficial focus of infection. In the second group, S. aureus was isolated from a deeper focus in 8 of 9 patients.
Conclusion: Mild forms of S. aureus toxin-mediated infection affect the pediatric population. Examination made it possible to distinguish an exanthema associated with an exfoliatin from one associated with a superantigen. This early clinical distinction results in differences in management.
Travaux originaux (français)
Medical table: A major tool for antimicrobial stewardship policy
Medical table: A major tool for antimicrobial stewardship policy
P-M Roger, E Demonchy, K Risso, J Courjon, S Leroux, E Leroux, É Cua
https://pubmed.ncbi.nlm.nih.gov/28457702/
Abstract
Infectious diseases are unpredictable, with heterogeneous clinical presentations, diverse pathogens, and various susceptibility rates to anti-infective agents. These features lead to a wide variety of clinical practices, which in turn strongly limits their evaluation. We have been using a medical table since 2005 to monitor the medical activity in our department. The observation of heterogeneous therapeutic practices led to drafting up our own antibiotic guidelines and to implementing a continuous evaluation of their observance and impact on morbidity and mortality associated with infectious diseases, including adverse effects of antibiotics, duration of hospital stay, use of intensive care, and deaths. The 10-year analysis of medical practices using the medical table is based on more than 10,000 hospitalizations. It shows simplified antibiotic therapies and a reduction in infection-related morbidity and mortality. The medical table is a major tool for antimicrobial stewardship, leading to constant benefits for patients.
Keywords: Antibiothérapie; Antibiotic therapy; Antimicrobial stewardship; Bacterial resistance; Bon usage des antibiotiques; Medical table; Résistance bactérienne; Tableau de bord.
Copyright © 2017 Elsevier Masson SAS. All rights reserved.
The impact of bacteremia on the outcome of bone infections
The impact of bacteremia on the outcome of bone infections
P-M Roger, E Cua, J Courjon, L Landraud, M Carles, E Bernard
https://pubmed.ncbi.nlm.nih.gov/25169941/
Abstract
We have used a medical database to analyze our activity since 2005. We observed a frequent association between bone and joint infection (BI) and bacteremia. Our aim was to characterize patients with BI and bacteremia, and focus on the outcome.
Patients and method: Our database includes the prospective recording of 28 characteristics of all hospitalized patients, including diagnosis, comorbid conditions, microbiological data, therapy, and outcome. We selected patients presenting with BI in this database, from July 2005 to December 2012. Fever before blood culture was retrospectively documented from the patient’s chart. Chronic BI was defined as a disease lasting more than 1 month. An unfavorable outcome was defined by the need for intensive care or death.
Results: Six hundred and thirty-two patients presented with BI and 125 with bacteremia (19.8%). We used a stepwise logistic regression analysis and determined that bacteremia was associated with vertebral osteomyelitis, OR, 3.97, P<0.001; alcohol abuse, OR, 2.51, P=0.010; fever, OR, 2.43, P<0.001; neurological and/or psychiatric diseases, OR, 2.41, P ≤ 0.001; and Staphylococcus aureus infection, OR, 2.32, P<0.001. The outcome was unfavorable in 23 cases (3.6%), associated with bacteremia, OR, 8.00, P<0.001, age> 60 years, OR, 4.78, P=0.018, and S. aureus infection, OR, 3.96, P=0.010. No single comorbid condition was significantly associated with an unfavorable outcome.
Conclusion: Bacteremia occurred in nearly 20% of the patients presenting with BI, and was associated with identifiable comorbid conditions; it was the main risk factor for an unfavorable outcome.
Keywords: Bacteremia; Bactériémie; Bone infection; Infection ostéoarticulaire; Outcome; Pronostic; Staphylococcus.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Travaux originaux avec participation aux groupes d’étude
Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results
Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results
WHO Solidarity Trial Consortium
https://pubmed.ncbi.nlm.nih.gov/33264556/
Abstract
Background: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs – remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a – in patients hospitalized with coronavirus disease 2019 (Covid-19).
Methods: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.
Results: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.
Conclusions: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).
Copyright © 2020 Massachusetts Medical Society.
Type 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study
Missed opportunities of HIV pre-exposure prophylaxis in France: a retrospective analysis in the French DAT'AIDS cohort
DAT’AIDS STUDY GROUP
https://pubmed.ncbi.nlm.nih.gov/30909885/
Abstract
Background: HIV pre-exposure prophylaxis (PrEP) was implemented in France in November 2015 based on individual-level risk factors for HIV infection. We evaluated the proportion of missed opportunities for PrEP among newly HIV-diagnosed people entering the Dat’AIDS cohort in 2016.
Methods: Multicenter retrospective analysis in 15 French HIV clinical centers of patients with a new diagnosis of HIV infection. Among them we differentiated patients according to the estimated date of infection: those occurring in the PrEP area (a previous negative HIV test in the last 12 months or those with an incomplete HIV-1 western blot (WB) with no HIV-1 anti-Pol-antibody at time of HIV diagnosis) and those in the pre-PrEP area (older infections). Epidemiological, biological and clinical data at HIV diagnosis were collected. Clinicians retrospectively identified potential eligibility for PrEP based on individual-level risk factors for HIV infection among those infected in the PrEP area.
Results: Among 966 patients with a new HIV diagnosis, 225 (23.3%) were infected in the PrEP area and 121 (53.8%) had complete data allowing evaluation of PrEP eligibility. Among them, 110 (91%) would have been eligible for PrEP, median age 31 years, with 68 (75.6%) born in France and 10 (11.1%) in Central/West Africa, with more than one previous STI in 19 (15.7%). The main eligibility criteria for PrEP were being a man who had sex with men or transgender 91 (82.7%) with at least one of the following criteria: unprotected anal sex with ≥2 partners in the last 6 months: 67 (60.9%); bacterial sexually transmitted infection in the last 12 months: 33 (30%); Use of psychoactive substances in a sexual context (chemsex): 16 (14.5%). PrEP was indicated for other HIV risk factors in 25 (22.7%).
Conclusion: With 91% (110/121) of patients infected in the PrEP area eligible for PrEP, this study highlights the high potential of PrEP in avoiding new infection in France but also shows a persistent delay in HIV testing. Thus, an important limit on PrEP implementation in France could be insufficient screening and care access.
Keywords: HIV; HIV testing; Missed opportunities; PrEP; Pre-exposure prophylaxis.
Integrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohort
Dat’AIDS Study Group
https://pubmed.ncbi.nlm.nih.gov/30534993/
Abstract
Objectives: To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs).
Methods: Patients in 18 HIV reference centres in France were prospectively included in the Dat’AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients’ characteristics related to discontinuation due to NPAEs were sought.
Results: INSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P < 0.001). Discontinuation for NPAEs occurred in 2.7%, 1.3% and 1.7% of the dolutegravir-, elvitegravir-, and raltegravir-treated patients, respectively (P < 0.001). In the multivariate analysis, discontinuation for NPAEs was related to dolutegravir versus elvitegravir (HR = 2.27; 95% CI 1.63-3.17; P < 0.0001) and versus raltegravir (HR = 2.46; 95% CI 2.00-3.40; P < 0.0001), but neither gender (HR for women = 1.19; 95% CI 0.97-1.46; P = 0.09) nor age (P = 0.12) was related. The association with abacavir was not retained in the final model.
Conclusions: Although discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.
© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.
Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study
Data Collection of Adverse Events of Anti-HIV drugs (D:A:D) Study group
https://pubmed.ncbi.nlm.nih.gov/29509305/
Abstract
Introduction: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV-positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study.
Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders.
Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti-hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow-up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti-hypertensives (1.17 [1.10, 1.25]).
Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV-positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions.
Keywords: Cardiovascular disease; HIV; cardiovascular disease interventions; cohort studies; gender; myocardial infarction; stroke; women.
© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.
Direct-acting antiviral treatment against hepatitis C virus infection in HIV-Infected patients - ``En route for eradication``?
Dat’AIDS study Group
https://pubmed.ncbi.nlm.nih.gov/28579302/
Abstract
Objectives: Direct-Acting Antivirals (DAAs) opened a new era in HCV treatment. We report the impact of HCV treatment in French HIV-HCV coinfected patients.
Methods: All HIV-HCV patients from the Dat’AIDS cohort followed between 2012 and 2015 were included. HCV status was defined yearly as naive, spontaneous cure, sustained virological response (SVR12), failure or reinfection.
Results: Among 32,945 HIV-infected patients, 15.2% were positive for anti-HCV antibodies. From 2012 to 2015, HCV incidence rate increased from 0.35%PY to 0.69%PY in MSM, while median incidence was 0.08%PY in other patients. Median reinfection rate was 2.56%PY in MSM and 0.22%PY in other patients. HCV treatment initiation rate rose from 8.2% in 2012 to 29.6% (48.0% in pre-treated patients vs 22.6% in naïve patients). SVR12 rate increased from 68.7% to 95.2%. By the end of 2015, 62.7% of the patients were cured either spontaneously or following SVR.
Conclusions: HCV treatment dramatically increased in HIV-HCV patients in France from 2012 to 2015 resulting in HCV cure in nearly two-thirds of the patients in this cohort. Combined with a declining HCV prevalence, the prevalence of active HCV infection among HIV patients will drastically decrease in the forthcoming years.
Keywords: Coinfection; DAA; Direct acting antiviral agent; Epidemiology; HCV; HIV; Treatment uptake.
Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study
MONALISA study group
https://pubmed.ncbi.nlm.nih.gov/28139432/
Abstract
Background: Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors.
Methods: MONALISA was a national prospective observational cohort study. We enrolled eligible cases declared to the National Reference Center for Listeria (all microbiologically proven) between Nov 3, 2009, and July 31, 2013, in the context of mandatory reporting. The outcomes were analysis of clinical features, characterisation of Listeria isolates, and determination of predictors of 3-month mortality or persisting impairment using logistic regression. A hierarchical clustering on principal components was also done for neurological and bacteraemic cases. The study is registered at ClinicalTrials.gov, number NCT01520597.
Findings: We enrolled 818 cases from 372 centres, including 107 maternal-neonatal infections, 427 cases of bacteraemia, and 252 cases of neurolisteriosis. Only five (5%) of 107 pregnant women had an uneventful outcome. 26 (24%) of 107 mothers experienced fetal loss, but never after 29 weeks of gestation or beyond 2 days of admission to hospital. Neurolisteriosis presented as meningoencephalitis in 212 (84%) of 252 patients; brainstem involvement was only reported in 42 (17%) of 252 patients. 3-month mortality was higher for bacteraemia than neurolisteriosis (hazard ratio [HR] 0·54 [95% CI 0·41-0·69], p<0·0001). For both bacteraemia and neurolisteriosis, the strongest mortality predictors were ongoing cancer (odds ratio [OR] 5·19 [95% CI 3·01-8·95], p<0·0001), multi-organ failure (OR 7·98 [4·32-14·72], p<0·0001), aggravation of any pre-existing organ dysfunction (OR 4·35 [2·79-6·81], p<0·0001), and monocytopenia (OR 3·70 [1·82-7·49], p=0·0003). Neurolisteriosis mortality was higher in blood-culture positive patients (OR 3·67 [1·60-8·40], p=0·002) or those receiving adjunctive dexamethasone (OR 4·58 [1·50-13·98], p=0·008).
Interpretation: The severity of listeriosis is higher than reported elsewhere. We found evidence of a significantly reduced survival in patients with neurolisteriosis treated with adjunctive dexamethasone, and also determined the time window for fetal losses. MONALISA provides important new data to improve management and predict outcome in listeriosis.
Funding: Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Travaux didactiques
Infections à VZV varicelle et zona / Infections à Herpès virus du sujet immunocompétent
Infections à VZV varicelle et zona / Infections à Herpès virus du sujet immunocompétent
Courjon J, Demochy E, Roger P-M
La revue du praticien avril 2017, tome 67, numéro 4, e183-e188
Leucoencéphalite multifocale progressive en hématologie
Leucoencéphalite multifocale progressive en hématologie.
Risso K, Courjon J.
Correspondance en onco-hématologie. Vol 11 n°2 Mars 2016
Lettres à la rédaction, cas cliniques, éditorial (anglais)
Extended Antibiotic Treatment Duration after DAIR
Extended Antibiotic Treatment Duration after DAIR
J Courjon, P Del Giudice
Clin Inf Dis 2020
Epidemiology of human common coronavirus acquisition in pilgrims
Epidemiology of human common coronavirus acquisition in pilgrims
Thi Loi Dao, Van Thuan Hoang, Tran Duc Anh Ly, Ndiaw Goumballa, Johan Courjon, Ziad Memish, Cheikh Sokhna, Didier Raoult, Philippe Parola, Philippe Gautret
Re: 'Pathogenesis and management of fracture-related infection' by Depypere et al
Re: ‘Pathogenesis and management of fracture-related infection’ by Depypere et al
R Manuello, R Ruimy, P Boileau, C Trojani, J Courjon
Direct-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge
Anne De Monte, Johan Courjon, Rodolphe Anty, Eric Cua, Alissa Naqvi, Véronique Mondain, Jacqueline Cottalorda, Laurence Ollier, Valérie Giordanengo
https://pubmed.ncbi.nlm.nih.gov/26967675/
Abstract
Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.
Keywords: HBV reactivation; HCV Direct-Acting Antivirals; HIV infection; NS3/4A protease inhibitors; NS5A inhibitors; NS5B polymerase inhibitors.
Copyright © 2016 Elsevier B.V. All rights reserved.
Safety of antibiotics combinations against Staphylococcal bone and joint infections
Safety of antibiotics combinations against Staphylococcal bone and joint infections
Agnès Danré, Johan Courjon, Evelyne Bernard, Eric Cua, Véronique Mondain, Pierre-Marie Roger
Lettres à la rédaction, cas cliniques, éditorial (français)
Erythematous skin nodules during treatment of Whipple's disease
Erythematous skin nodules during treatment of Whipple’s disease
A Sanchez, P Del Giudice, C Mantion, S Mazellier, F Boukari, P-M Roger, J Courjon
https://pubmed.ncbi.nlm.nih.gov/33075401/
Keywords: Dermatology; Erythematous nodules; Immune reconstitution inflammatory syndrome; Infectious disease; Whipple disease.
Severe intestinal obstruction due to Strongyloides stercoralis in a pregnant woman
Severe intestinal obstruction due to Strongyloides stercoralis in a pregnant woman
A Malézieux-Picard, M C Saint-Paul, J Dellamonica, J Courjon, N Tieulié, P Marty, J G Fuzibet, R Collomp, J A Marinho, V Queyrel
https://pubmed.ncbi.nlm.nih.gov/28651833/
Keywords: HTLV-1; Intestinal obstruction; Occlusion intestinale; Strongyloides stercoralis.
Antimicrobial stewardship policy: time to revisit the strategy?
Antimicrobial stewardship policy: time to revisit the strategy?
P-M Roger, J Courjon, S Léotard, C Déchamp, N Négrin, M Vassallo; Network for Infectious Diseases Paca-Est
https://pubmed.ncbi.nlm.nih.gov/26387088/
Abstract
Recent data indicate that both the overall numbers of antibiotic prescription and the frequency of multidrug-resistant bacteria are increasing significantly. These threatening features are observed, despite national antimicrobial stewardship (AMS) policies aimed at decreasing antibiotic use. AMS should also focus on the initial steps leading to antibiotic prescription. Physicians and their patients should benefit from the structured clinical pathways, the latter being adapted to regional epidemiological data and resources. Continuous evaluation of these predefined clinical paths through a computerized medical dashboard will allow a critical review and finally the optimization of medical practices. These innovative behavioural approaches for clinicians will supply precise information on the relationship among the diagnosis, therapeutics and outcome. This changing environment will carry out the adapted therapeutic procedures, and appropriate antibiotic use will inherently improve.
Orateur invité
- Diagnostic d’une infection : 24/24 est-ce nécessaire. Journée nationale de formation des paramédicaux en infectiologie. JNI 2020
- Évaluation de la prise en charge des infections ostéo-articulaires complexes en France: audit national communication orale en plénière pour le congrès CRIOAC 2019
Hors invitation
- Perfusion continue de cloxacilline au cours des IOA à aureus RICAI 2018
Brevets en lien avec les travaux menés au laboratoire Inserm sur l’inflammasome NLRP3 au cours des infections virales et bactériennes
EP193005502.7 (2019) “Methods and composition for treatment of NLRP3 inflammasome mediated IL-1beta dependent disorders”.
EP20315109.7 (2020) “Methods and compositions for treatment of SARS-CoV-2 infection”
EP20305782.3 (2020) “Methods and pharmaceutical composition for the treatment of infectious diseases »
EP20306245.0 (2020) “Methods for diagnosis and monitoring form of coronavirus infection”
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Publications
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Score SIGAPS mars 2021 : 500
Travaux originaux (anglais)
Publications 2021 du Dr COURJON Johan
Clinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 PandemicClinical, Laboratory, and Interferon-Alpha Response Characteristics of Patients With Chilblain-like Lesions During the COVID-19 Pandemic
Thomas Hubiche, Nathalie Cardot-Leccia, Florence Le Duff, Barbara Seitz-Polski, Pascal Giordana, Christine Chiaverini, Valérie Giordanengo, Géraldine Gonfrier, Vincent Raimondi, Olivier Bausset, Zoubir Adjtoutah, Margaux Garnier, Fanny Burel-Vandenbos, Bérengère Dadone-Montaudié, Véréna Fassbender, Aurélia Palladini, Johan Courjon, Véronique Mondain, Julie Contenti, Jean Dellamonica, Georges Leftheriotis, Thierry Passeron
https://pubmed.ncbi.nlm.nih.gov/33237291/
Abstract
Importance: Chilblain-like lesions have been reported during the coronavirus 2019 (COVID-19) pandemic. The pathophysiology of such manifestations remains largely unknown.
Objective: To perform a systematic clinical, histologic, and biologic assessment in a cohort of patients with chilblain-like lesions occurring during the COVID-19 pandemic.
Design, setting, and participants: In this prospective case series carried out with a COVID-19 multidisciplinary consultation group at the University Hospital of Nice, France, 40 consecutive patients presenting with chilblain-like lesions were included.
Main outcomes and measures: Patients underwent a thorough general and dermatologic examination, including skin biopsies, vascular investigations, biologic analyses, interferon-alpha (IFN-α) stimulation and detection, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) and serologic analysis.
Results: Overall, 40 consecutive patients with chilblain-like lesions were included. Most patients were young, with a median (range) age of 22 (12-67) years; 19 were male and 21 were female. The clinical presentation was highly reproducible with chilblain-like lesions mostly on the toes. Bullous and necrotic evolution was observed in 11 patients. Acrocyanosis or cold toes were reported in 19 (47.5%) cases. Criteria compatible with COVID-19 cases were noted in 11 (27.5%) within 6 weeks prior to the eruption. The real-time PCR (rt-PCR) testing results were negative in all cases. Overall, SARS-CoV-2 serology results were positive in 12 patients (30%). D-dimer concentration levels were elevated in 24 (60.0%) cases. Cryoglobulinemia and parvovirus B19 serologic results were negative for all tested patients. The major histologic findings were features of lymphocytic inflammation and vascular damage with thickening of venule walls and pericyte hyperplasia. A significant increase of IFN-α production after in vitro stimulation was observed in the chilblain population compared with patients with mild-severe acute COVID-19.
Conclusions and relevance: Taken together, our results suggest that chilblain-like lesions observed during the COVID-19 pandemic represent manifestations of a viral-induced type I interferonopathy.
Trial registration: ClinicalTrials.gov Identifier: NCT04344119.
CloseEscherichia coli Rho GTPase-activating toxin CNF1 mediates NLRP3 inflammasome activation via p21-activated kinases-1/2 during bacteraemia in miceEscherichia coli Rho GTPase-activating toxin CNF1 mediates NLRP3 inflammasome activation via p21-activated kinases-1/2 during bacteraemia in mice
Océane Dufies, Anne Doye, Johan Courjon, Cédric Torre, Gregory Michel, Celine Loubatier, Arnaud Jacquel, Paul Chaintreuil, Alissa Majoor, Rodolphe R Guinamard, Alexandre Gallerand, Pedro H V Saavedra, Els Verhoeyen, Amaury Rey, Sandrine Marchetti, Raymond Ruimy, Dorota Czerucka, Mohamed Lamkanfi, Bénédicte F Py, Patrick Munro, Orane Visvikis, Laurent Boyer
https://pubmed.ncbi.nlm.nih.gov/33432150/
Abstract
Inflammasomes are signalling platforms that are assembled in response to infection or sterile inflammation by cytosolic pattern recognition receptors. The consequent inflammasome-triggered caspase-1 activation is critical for the host defence against pathogens. During infection, NLRP3, which is a pattern recognition receptor that is also known as cryopyrin, triggers the assembly of the inflammasome-activating caspase-1 through the recruitment of ASC and Nek7. The activation of the NLRP3 inflammasome is tightly controlled both transcriptionally and post-translationally. Despite the importance of the NLRP3 inflammasome regulation in autoinflammatory and infectious diseases, little is known about the mechanism controlling the activation of NLRP3 and the upstream signalling that regulates the NLRP3 inflammasome assembly. We have previously shown that the Rho-GTPase-activating toxin from Escherichia coli cytotoxic necrotizing factor-1 (CNF1) activates caspase-1, but the upstream mechanism is unclear. Here, we provide evidence of the role of the NLRP3 inflammasome in sensing the activity of bacterial toxins and virulence factors that activate host Rho GTPases. We demonstrate that this activation relies on the monitoring of the toxin’s activity on the Rho GTPase Rac2. We also show that the NLRP3 inflammasome is activated by a signalling cascade that involves the p21-activated kinases 1 and 2 (Pak1/2) and the Pak1-mediated phosphorylation of Thr 659 of NLRP3, which is necessary for the NLRP3-Nek7 interaction, inflammasome activation and IL-1β cytokine maturation. Furthermore, inhibition of the Pak-NLRP3 axis decreases the bacterial clearance of CNF1-expressing UTI89 E. coli during bacteraemia in mice. Taken together, our results establish that Pak1 and Pak2 are critical regulators of the NLRP3 inflammasome and reveal the role of the Pak-NLRP3 signalling axis in vivo during bacteraemia in mice.
CloseFunctional Exhaustion of Type I and II Interferons Production in Severe COVID-19 PatientsFunctional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients
Functional Exhaustion of Type I and II Interferons Production in Severe COVID-19 Patients
Caroline Ruetsch, Vesna Brglez, Marion Crémoni, Kévin Zorzi, Céline Fernandez, Sonia Boyer-Suavet, Sylvia Benzaken, Elisa Demonchy, Karine Risso, Johan Courjon, Eric Cua, Carole Ichai, Jean Dellamonica, Thierry Passeron, Barbara Seitz-Polski
https://pubmed.ncbi.nlm.nih.gov/33585507/
Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan in December 2019 and has since spread across the world. Even though the majority of patients remain completely asymptomatic, some develop severe systemic complications. In this prospective study we compared the immunological profile of 101 COVID-19 patients with either mild, moderate or severe form of the disease according to the WHO classification, as well as of 50 healthy subjects, in order to identify functional immune factors independently associated with severe forms of COVID-19. Plasma cytokine levels, and cytokine levels upon in vitro non-specific stimulation of innate and adaptive immune cells, were measured at several time points during the course of the disease. As described previously, inflammatory cytokines IL1β, IL6, IL8, and TNFα associated with cytokine storm were significantly increased in the plasma of moderate and severe COVID-19 patients (p < 0.0001 for all cytokines). During follow-up, plasma IL6 levels decreased between the moment of admission to the hospital and at the last observation carried forward for patients with favorable outcome (p = 0.02148). After in vitro stimulation of immune cells from COVID-19 patients, reduced levels of both type I and type II interferons (IFNs) upon in vitro stimulation were correlated with increased disease severity [type I IFN (IFNα): p > 0.0001 mild vs. moderate and severe; type II IFN (IFNγ): p = 0.0002 mild vs. moderate and p < 0.0001 mild vs. severe] suggesting a functional exhaustion of IFNs production. Stimulated IFNα levels lower than 2.1 pg/ml and IFNγ levels lower than 15 IU/mL at admission to the hospital were associated with more complications during hospitalization (p = 0.0098 and p =0.0002, respectively). A low IFNγ level was also confirmed by multivariable analysis [p = 0.0349 OR = 0.98 (0.962; 0.999)] as an independent factor of complications. In vitro treatment with type IFNα restored type IFNγ secretion in COVID-19 patients while the secretion of pro-inflammatory cytokines IL6 and IL1β remained stable or decreased, respectively. These results (a) demonstrate a functional exhaustion of both innate and adaptive immune response in severe forms of COVID-19; (b) identify IFNα and IFNγ as new potential biomarkers of severity; and (c) highlight the importance of targeting IFNs when considering COVID-19 treatment in order to re-establish a normal balance between inflammatory and Th1 effector cytokines.
Keywords: COVID-19; immunology; infectious diseases; interferon; personalized medicine.
Copyright © 2021 Ruetsch, Brglez, Crémoni, Zorzi, Fernandez, Boyer-Suavet, Benzaken, Demonchy, Risso, Courjon, Cua, Ichai, Dellamonica, Passeron and Seitz-Polski.
CloseHeterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severityHeterogeneous NLRP3 inflammasome signature in circulating myeloid cells as a biomarker of COVID-19 severity
Johan Courjon, Océane Dufies, Alexandre Robert, Laurent Bailly, Cédric Torre, David Chirio, Julie Contenti, Sébastien Vitale, Céline Loubatier, Anne Doye, Christelle Pomares-Estran, Géraldine Gonfrier, Romain Lotte, Patrick Munro 1, Orane Visvikis, Jean Dellamonica, Valérie Giordanengo, Michel Carles, Laurent Yvan-Charvet, Stoyan Ivanov, Patrick Auberger, Arnaud Jacquel, Laurent Boyer
https://pubmed.ncbi.nlm.nih.gov/33683342/
Abstract
Dysregulated immune response is the key factor leading to unfavorable coronavirus disease 2019 (COVID-19) outcome. Depending on the pathogen-associated molecular pattern, the NLRP3 inflammasome can play a crucial role during innate immunity activation. To date, studies describing the NLRP3 response during severe acute respiratory syndrome coronavirus 2 infection in patients are lacking. We prospectively monitored caspase-1 activation levels in peripheral myeloid cells from healthy donors and patients with mild to critical COVID-19. The caspase-1 activation potential in response to NLRP3 inflammasome stimulation was opposed between nonclassical monocytes and CD66b+CD16dim granulocytes in severe and critical COVID-19 patients. Unexpectedly, the CD66b+CD16dim granulocytes had decreased nigericin-triggered caspase-1 activation potential associated with an increased percentage of NLRP3 inflammasome impaired immature neutrophils and a loss of eosinophils in the blood. In patients who recovered from COVID-19, nigericin-triggered caspase-1 activation potential in CD66b+CD16dim cells was restored and the proportion of immature neutrophils was similar to control. Here, we reveal that NLRP3 inflammasome activation potential differs among myeloid cells and could be used as a biomarker of a COVID-19 patient’s evolution. This assay could be a useful tool to predict patient outcome. This trial was registered at www.clinicaltrials.gov as #NCT04385017.
© 2021 by The American Society of Hematology.
CloseManagement of prosthetic joint infections in France: a national audit to identify key situations requiring innovation and homogenizationManagement of prosthetic joint infections in France: a national audit to identify key situations requiring innovation and homogenization
Marion Le Maréchal, Zoé Cavalli, Cécile Batailler, Jean-François Gonzalez, André Ferreira, Sébastien Lustig, Tristan Ferry, Johan Courjon
https://pubmed.ncbi.nlm.nih.gov/33933020/
Abstract
Background: Prosthetic joint infections (PJI) are one of the most serious complication of arthroplasty. The management of PJI needs a multidisciplinary collaboration between orthopaedic surgeon, infectious disease specialist and microbiologist. In France, the management of PJI is organized around reference centres (CRIOACs). Our main objective was to perform an audit through a questionnaire survey based on clinical cases, to evaluate how French physicians manage PJI. Eligible participants were all physicians involved in care of patients presenting a PJI. Physicians could answer individually, or collectively during a multidisciplinary team meeting dedicated to PJI. The survey consisted as three questionnaires organized in a total of six clinical cases.
Results: Answers from the CRIOACs to the three questionnaires were 92, 77, and 53%. Between 32 and 39% of respondents did not administer antibiotic prophylaxis despite positive S. aureus pre-operative documentation. One-stage exchange strategy was widely preferred in all clinical cases, with no difference between CRIOACs and other centres. Rifampicin was prescribed for S. aureus PJI, in a situation with (90-92%) or without any prosthesis (70%). There was no consensus for the total antibiotic regimen duration, with prescriptions from six to 12 weeks for a majority of respondents.
Conclusions: Surgical strategy for the management of PJI was homogenous with a preference for a one-stage exchange strategy. Medical management was more heterogenous, which reflects the heterogeneity of those infections and difficulties to perform studies with strong conclusions.
Keywords: Arthritis infection; Clinical audit; Joint prosthesis; Rifampin; Staphylococcus aureus; Surveys and questionnaires.
CloseProteinuria as a Biomarker for COVID-19 SeverityProteinuria as a Biomarker for COVID-19 Severity
Proteinuria as a Biomarker for COVID-19 Severity
Hajar Ouahmi, Johan Courjon, Lucas Morand, Juliette François, Vincent Bruckert, Romain Lombardi, Vincent Esnault, Barbara Seitz-Polski, Elisa Demonchy, Jean Dellamonica, Sonia Boyer-Suavet
https://pubmed.ncbi.nlm.nih.gov/33767630/
Abstract
Background: Renal involvement in syndrome coronavirus 2 (SARS-CoV-2) infection has been retrospectively described, especially acute kidney injury (AKI). However, quantitative proteinuria assessment and its implication in coronavirus disease 2019 (COVID-19) remain unknown.
Methods: In this prospective, multicenter study in France, we collected clinical and biological data including urinary protein to creatine ratio (UPCR) in patients presenting with moderate to severe COVID-19. Clinical outcome was analyzed according to the level of UPCR.
Results: 42/45 patients (93.3%) had renal involvement (abnormal urinary sediment and/or AKI). Significant proteinuria occurred in 60% of patients. Urine protein electrophoresis showed tubular protein excretion in 83.8% of patients with proteinuria. Inflammatory parametersand D-dimer concentrations correlated with proteinuria level. Patients who required intensive care unit (ICU) admission had higher proteinuria (p = 0.008). On multivariate analysis, proteinuria greater than 0.3 g/g was related to a higher prevalence of ICU admission [OR = 4.72, IC95 (1.16-23.21), p = 0.03], acute respiratory distress syndrome (ARDS) [OR = 6.89, IC95 (1.41-53.01, p = 0.02)], nosocomial infections [OR = 3.75, IC95 (1.11-13.55), p = 0.03], longer inpatient hospital stay (p = 0.003).
Conclusion: Renal involvement is common in moderate to severe SARS-CoV-2 infection. Proteinuria at baseline is an independent risk factor for increased hospitalization duration and ICU admission in patients with COVID-19.
Keywords: COVID-19; SARS-CoV-2; acute kidney injury; biomarker; kidney involvement; pronostic and predictive factors; proteinuria.
Copyright © 2021 Ouahmi, Courjon, Morand, François, Bruckert, Lombardi, Esnault, Seitz-Polski, Demonchy, Dellamonica and Boyer-Suavet.
ClosePublications 2020 du Dr COURJON Johan
A Population Pharmacokinetic Analysis of Continuous Infusion of Cloxacillin during Staphylococcus aureus Bone and Joint InfectionsA Population Pharmacokinetic Analysis of Continuous Infusion of Cloxacillin during Staphylococcus aureus Bone and Joint Infections
Johan Courjon, Margaux Garzaro, Pierre-Marie Roger, Raymond Ruimy, Thibaud Lavrut, Mikaël Chelli, Jean-Luc Raynier, David Chirio, Elisa Demonchy, Laura Cabane, François Jehl, Christophe Trojani, Antoine Grillon, Sylvain Goutelle
https://pubmed.ncbi.nlm.nih.gov/32988822/
Abstract
Intravenous administration of antibiotics is recommended during the early phase of methicillin-susceptible S. aureus (MSSA) bone and joint infection (BJI). We sought to compare the plasma concentrations of cloxacillin administered alternately by continuous and intermittent infusion (CI and ItI) in patients with MSSA BJI. In this prospective crossover trial, patients were randomly assigned to receive either 3 days of CI (two 75-mg/kg 12-h cloxacillin infusions per day) and then 3 days of ItI (four 37.5-mg/kg 1-h cloxacillin infusions per day) or vice versa. The drug concentration measurement was performed on day 3 of each type of administration at 1, 6, and 11 h and at 1, 2, 3, 4, and 6 h after the beginning of CI and ItI, respectively. We used the nonparametric algorithm NPAG to estimate population pharmacokinetic (PK) parameters. The final model was used to perform pharmacokinetic/pharmacodynamic (PK/PD) simulations and calculate the probabilities of target attainment (PTA) for several ItI and CI dosing regimens. We considered two PK/PD targets of time spent above the MIC for free cloxacillin concentrations (fT>MIC): 50 and 100%. Eighty-four concentrations from 11 patients were analyzed. A two-compartment model adequately described the data. ItI with q6h regimens and short 1-h infusions of 2,000 or 3,000 mg were associated with low PTA, even for the low target (50% fT>MIC) while 3-h infusions and continuous infusions (6 to 12 g/day) were associated with a PTA of >90% for an MIC up to 0.5 mg/liter. These results support the use of prolonged or continuous infusion of cloxacillin in patients with BJI.
Keywords: Staphylococcus aureus; antibiotics; bone and joint infections; cloxacillin; continuous infusion; osteomyelitis; penicillin; pharmacodynamic; pharmacokinetics; population PK analysis; population pharmacokinetics.
Copyright © 2020 American Society for Microbiology.
CloseHydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trialHydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
Philippe Gautret, Jean-Christophe Lagier, Philippe Parola, Van Thuan Hoang, Line Meddeb, Morgane Mailhe, Barbara Doudier, Johan Courjon, Valérie Giordanengo, Vera Esteves Vieira, Hervé Tissot Dupont, Stéphane Honoré, Philippe Colson, Eric Chabrière, Bernard La Scola, Jean-Marc Rolain, Philippe Brouqui, Didier Raoult
https://pubmed.ncbi.nlm.nih.gov/32205204/
Abstract
Background: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the effect of hydroxychloroquine on respiratory viral loads.
Patients and methods: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point.
Results: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported in the litterature for untreated patients. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination.
Conclusion: Despite its small sample size, our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.
Keywords: 2019-nCoV; Azithromycin; COVID-19; Clinical trial; Hydroxychloroquine; SARS-CoV-2.
Copyright © 2020. Published by Elsevier B.V.
CloseQT Interval Prolongation Under Hydroxychloroquine/Azithromycin Association for Inpatients With SARS-CoV-2 Lower Respiratory Tract InfectionQT Interval Prolongation Under Hydroxychloroquine/Azithromycin Association for Inpatients With SARS-CoV-2 Lower Respiratory Tract Infection
Sok-Sithikun Bun, Philippe Taghji, Johan Courjon, Fabien Squara, Didier Scarlatti, Guillaume Theodore, Delphine Baudouy, Benjamin Sartre, Mohamed Labbaoui, Jean Dellamonica, Denis Doyen, Charles-Hugo Marquette, Jacques Levraut, Vincent Esnault, Sok-Siya Bun, Emile Ferrari
https://pubmed.ncbi.nlm.nih.gov/32588427/
Abstract
Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia’s correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24th to April 20th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.
© 2020 The Authors Clinical Pharmacology & Therapeutics © 2020 American Society for Clinical Pharmacology and Therapeutics.
ClosePublications 2019 du Dr COURJON Johan
Adherence to antibiotic guidelines for erysipelas or cellulitis is associated with a favorable outcomeAdherence to antibiotic guidelines for erysipelas or cellulitis is associated with a favorable outcome
Camille Klotz, Johan Courjon, Céline Michelangeli, Elisa Demonchy, Raymond Ruimy, Pierre-Marie Roger
https://pubmed.ncbi.nlm.nih.gov/30685804/
Abstract
Outside areas of S. aureus strains resistant to methicillin (MRSA) in the community, no studies showed a relationship between the treatment for erysipelas or cellulitis and the outcome. We aimed to measure the impact of an internal therapeutic protocol, based on national guidelines on patients’ outcome. This study was based on the dashboard of the infectious diseases department, which prospectively includes 28 parameters for all admitted patients. We included community-acquired erysipelas and cellulitis; exclusion criteria were abscesses at admission; ear, nose, throat, or dental cellulitis; pyomyositis; and length of stay ≤ 2 days. Adherence to guidelines was defined by the use of amoxicillin, amoxicillin/clavulanic acid, clindamycin, or pristinamycin, alone or in combination or successively. A poor outcome was defined by surgical procedure or intensive care requirement or death occurring after 5 days or more of antibiotic therapy. From July 2005 to June 2017, 630 cases of erysipelas or cellulitis were included. Blood cultures performed in 567 patients (90%) were positive in 39 cases (6.9%). Adherence rate to guidelines was 65% (410 cases). A poor outcome was recorded in 54 (8.5%) patients, less frequently in case of adherence to guidelines: 26/410 (6.3%) vs 28/220 (12.7%), p = 0.007. In logistic regression analysis, two risk factors were associated with a poor outcome: peripheral arterial disease, AOR 4.80 (2.20-10.49); and bacteremia, AOR 5.21 (2.31-11.76), while guideline adherence was the only modifiable protective factor, OR 0.48 (0.26-0.89). In erysipelas and cellulitis, adherence to guidelines was associated with a favorable outcome.
Keywords: Antibiotic therapy; Cellulitis; Erysipelas; Guidelines; Outcome; SSTI.
CloseAmoxicillin/clavulanic acid+aminoglycoside as empirical antibiotic treatment in severe community-acquired infections with diagnostic uncertaintyAmoxicillin/clavulanic acid+aminoglycoside as empirical antibiotic treatment in severe community-acquired infections with diagnostic uncertainty
Johan Courjon, David Chirio, Elisa Demonchy, Céline Michelangeli, Nicolas Degand, Pierre-Marie Roger
https://pubmed.ncbi.nlm.nih.gov/30707379/
Abstract
Diagnostic uncertainty is common in the emergency room and multidrug-resistant bacteria emerge in the community setting, implying to establish the most efficient empirical antibiotic therapy (eEAT). Our aim was to identify such eEAT, considering that in case of DU with severe clinical presentation, most prescribers would propose an empiric combination (EC). The medical dashboard of our ward records prospectively 28 characteristics of each hospitalization including hospitalization motive, final diagnosis, and all antibiotics prescribed. All patients with community-acquired bacteremia (CAB) were included. DU was defined by a discrepancy between suspected diagnosis in the emergency room and final diagnosis. eEAT was defined by in vitro activity of at least one prescribed compound. Finally, independently from the dashboard, we retrospectively compared 2 CTs: amoxicillin/clavulanic acid (AMC)+gentamicin (G) and cefotaxime (3GC)+G. One thousand thirty-four patients with a final diagnosis of CAB were identified from July 2005 to June 2018, including 357 DU (35%) at baseline. eEAT (n = 553) was associated with a trend towards a lower death rate compared to inefficient therapies: 5.4 vs 10.0% (p = 0.053), and effective antibiotic reassessment was the most protective factor against an unfavorable outcome: 0.34 (0.16-0.71). Bacteria involved in case of UD were resistant to AMC+G and to 3GC+G in 8.1% and 12.8% of patients, respectively. Diagnostic uncertainty was a frequent event requiring antibiotic reassessment. As the latter was not systematically realized, the best eEAT is required and AMC+aminoglycoside should be considered.
Keywords: Bacteremia; Community-acquired infection; ESBL Enterobacteriaceae; Empirical antibiotic therapy; Outcome.
CloseFrench national cohort of first use of dalbavancin: A high proportion of off-label useFrench national cohort of first use of dalbavancin: A high proportion of off-label use
French national cohort of first use of dalbavancin: A high proportion of off-label use
Aurélien Dinh, Clara Duran, Patricia Pavese, Lydie Khatchatourian, Boris Monnin, Alexandre Bleibtreu, Eric Denis, Cédric Etienne, Nicolas Rouanes, Rafael Mahieu, Frédérique Bouchand, Benjamin Davido, Romain Lotte, Philippe Cabaret, Fabrice Camou, Pascal Chavanet, Assi Assi, Silvia Limonta, Catherine Lechiche, Raphaëlle Riou, Johan Courjon, Gabriela Illes, Flore Lacassin-Beller, Eric Senneville; Dalbavancin French Study Group
https://pubmed.ncbi.nlm.nih.gov/31400471/
Abstract
Dalbavancin is a glycopeptide antibiotic with a long half-life, recently marketed in Europe for skin and soft-tissue infections (SSTIs), but its real-life use is not well known. The aim of this study was to describe all first prescriptions in France over an 16-month period. A retrospective study on all adult patients receiving at least one dose of dalbavancin from 1 June 2017 to 31 September 2018 was performed (75 patients from 29 French hospitals). Data were collected via a standard questionnaire. Failure was defined as persistence or reappearance of signs of infection, and/or switch to suppressive antibiotic treatment, and/or death from infection. The main indications were bone and joint infection (BJI) (64.0%), endocarditis (25.3%), and SSTI (17.3%). The main bacteria involved were Staphylococcus aureus (51.4%), including methicillin-resistant S. aureus (MRSA) (19.4%), and coagulase-negative staphylococci (44.4%). Median minimum inhibitory concentrations (MICs) for staphylococci to vancomycin and dalbavancin ranged from 0.875-2.0 mg/L and 0.032-0.064 mg/L, respectively. Dalbavancin was used after a mean of 2.3 ± 1.2 lines of antimicrobial treatment. The main treatment regimens for dalbavancin were a two-dose regimen (1500 mg each) in 38 cases (50.7%) and a single-dose regimen (1500 mg) in 13 cases (17.3%). Overall, at the patient’s last visit, clinical cure was observed in 54/68 patients, whilst failure was observed in 14/68 patients. First use of dalbavancin in France was mostly off-label. Most were due to BJI, often as rescue therapy for severe infections. Even in off-label situations, dalbavancin appears safe and effective.
Keywords: Bone and joint infection; Dalbavancin; Endocarditis; Off-label; Staphylococci.
Copyright © 2019 Elsevier Ltd. All rights reserved.
CloseInfectious disease symptoms and microbial carriage among French medical students travelling abroad: A prospective studyInfectious disease symptoms and microbial carriage among French medical students travelling abroad: A prospective study
Thi Loi Dao, Van Thuan Hoang, Tran Duc Anh Ly, Amal Magmoun, Naomie Canard, Tassadit Drali, Florence Fenollar, Laetitia Ninove, Didier Raoult, Philippe Parola, Johan Courjon, Philippe Gautret
https://pubmed.ncbi.nlm.nih.gov/31870880/
Abstract
Background: In France, no previous studies have focused specifically on health problems among medical students during internships abroad including the clinical symptoms suggestive of infectious diseases and the acquisition of pathogen carriage.
Methods: Clinical follow up and qPCR based respiratory, gastrointestinal and vaginal pathogen carriage before and after travel were prospectively assessed in a cohort of medical students departing from Marseille, France.
Results: 134 students were included. 73.9%, 38.8% and 5.0% of students reported gastrointestinal, respiratory and vaginal symptoms, respectively. The acquisition rate of Enteroaggregative Escherichia coli (EAEC) and Enteropathogenic E. coli (EPEC) was 53% and 41%, respectively. The acquisition of respiratory viruses was low but associated with persisting symptoms, while bacterial acquisition ranged from 3.3% for Streptococcus pyogenes to 15.0% for Haemophilus influenzae. Gardnerella vaginalis and Atopobium vaginae acquisition rates were 7.7% and 14.3% respectively. Five students (5.1%) had molecular quantification criteria for bacterial vaginosis on return.
Conclusion: This preliminary study demonstrates that besides the known risk of gastrointestinal and respiratory infections and associated changes in intestinal and respiratory microbiota, medical students abroad may also experience changes in vaginal microbiota leading, in some cases, to clinical symptoms or the acquisition of bacterial vaginosis, which may be asymptomatic.
Keywords: Bacterial vaginosis; Gastrointestinal infection; Medical students; Microbial carriage; Respiratory infection; Travellers.
Copyright © 2019 Elsevier Ltd. All rights reserved.
ClosePublications 2018 du Dr COURJON Johan
A toolkit for the management of infection or colonization by extended-spectrum beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome of a European projectA toolkit for the management of infection or colonization by extended-spectrum beta-lactamase producing Enterobacteriaceae in Italy: implementation and outcome of a European project
V Mondain, G Secondo, R Guttmann, G Ferrea, A Dusi, M Giacomini, J Courjon, C Pradier
https://pubmed.ncbi.nlm.nih.gov/29600324/
Abstract
Among European countries, prevalence rates of extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) are particularly high in those bordering the Mediterranean. This is the case for Italy, with 26% of Escherichia coli displaying resistance to the 3rd generation cephalosporins in 2013. An ESBL-E toolkit designed to assist clinicians in managing patients harboring ESBL-E was favorably implemented in Southern France. In a context of lack of specific Italian recommendations, its extension to an adjacent region of Italy was made possible through a cross-border EU cooperation program. Italian infectious disease (ID) specialists, microbiologists, and community-based general practitioners from three districts in Liguria were offered a toolkit consisting in a warning system and detailed procedures for the management of patients harboring ESBL-E, including seeking advice from an ID specialist, and were trained during 52 video conferences by an experienced French team. Indications and trends in antimicrobial prescription were studied following implementation of the toolkit. Between November 2013 and November 2014, 476 patients were identified as harboring ESBL-E and expert advice was sought for 364 of these; all patients and/or their caregivers were advised on appropriate hygiene measures and 209/341 with documented management received antimicrobial treatment, while asymptomatic carriers (39%) were not prescribed antibiotics. The ESBL-E toolkit was well received by the healthcare staff. A specific, simple tool consisting in a care-bundle approach to manage ESBL-E carriers can restrict antimicrobial prescription to symptomatic patients while raising awareness among caregivers of the importance of seeking expert advice and implementing appropriate hygiene measures.
CloseCefoxitin-based antibiotic therapy for extended-spectrum β-lactamase-producing Enterobacteriaceae prostatitis: a prospective pilot studyCefoxitin-based antibiotic therapy for extended-spectrum β-lactamase-producing Enterobacteriaceae prostatitis: a prospective pilot study
Elisa Demonchy, Johan Courjon, Estelle Ughetto, Matthieu Durand, Karine Risso, Rodolphe Garraffo, Pierre-Marie Roger
https://pubmed.ncbi.nlm.nih.gov/29378342/
Abstract
The emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis.
Keywords: Acute bacterial prostatitis; Carbapenem-sparing regimen; Cefoxitin; Chronic bacterial prostatitis; ESBL-producing Enterobacteriaceae; Prostatitis.
Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.
CloseFast track consultation in the infectious diseases department of a French university hospital: evaluation of the service delivered to the general practitionerFast track consultation in the infectious diseases department of a French university hospital: evaluation of the service delivered to the general practitioner
Nicolas Weiss, Johan Courjon, Christian Pradier, Cécile Caisso, Véronique Mondain, Pierre-Marie Roger, Elisa Demonchy
https://pubmed.ncbi.nlm.nih.gov/28829214/
Abstract
Purpose: Since 2010, the Infectious Diseases (ID) department of the Nice university hospital (France) has implemented a fast track consultation (FTC): it allows General Practitioners (GP) to directly reach an ID specialist through a dedicated phone number for initial advice. Depending on the first observation, a formal consultation can be planned within 48 h. Our aim was to evaluate in a pilot study, the contribution of the FTC regarding the management of patients 28 days after the first phone contact.
Methods: This prospective current care study was conducted between November 2014 and January 2015 in our ID department. The GP indicates the most likely diagnosis, the therapeutic strategy and the patient’s management he would have applied. After the formal consultation, ID specialist provides his diagnosis, therapeutic strategy and patient’s management. An adjudicative committee has evaluated the benefit of the FTC after 28 days of follow-up.
Results: Fifty-one patients referred by 49 GP were included. ID specialists modified the diagnosis in 22 (43%) patients, antibiotic treatment in 35 (68%) and treatment plan in 30 patients (59%). FTC provided at least one service for 41/51 patients (94%): antibiotic treatment was reassessed for 11 (22%) patients, averted for 9 (18%) patients, unnecessary hospitalization was avoided for 8 (16%) of them and emergency room visit averted for 5 (10%) patients.
Conclusions: FTC can provide significant improvement in the management of the patients in terms of decrease in unnecessary hospitalization, emergency room visit averted and appropriate use of antibiotics.
Keywords: Infectious disease advice; ambulatory medicine; appropriate antibiotherapy; fast track consultation; general practitioner; outpatients.CloseManaging ESBL-producing Enterobacteriaceae-related urinary tract infection in primary care: a tool kit for general practitionersManaging ESBL-producing Enterobacteriaceae-related urinary tract infection in primary care: a tool kit for general practitioners
Aurélie Zucconi, Johan Courjon, Christophe Maruéjouls, Fabrice Saintpère, Nicolas Degand, Lilli Pandiani, Christian Pradier, Véronique Mondain
https://pubmed.ncbi.nlm.nih.gov/29594799/
Abstract
In Southern France, approximately 4% of E. coli isolates from community-acquired urinary tract infections are extended spectrum beta-lactamase producers, while carriage rates for enterobacteriaceae (ESBL-E) range from 3 to 6%. General practitioners (GP) are unfamiliar with the management of patients harboring ESBL-E. Providing them with a specific tool kit should assist in their therapeutic approach and optimize antimicrobial prescription an ESBL-E tool kit was developed by a multidisciplinary team: infectious diseases (ID) specialists, microbiologists, pharmacologists, and nursing home staff. This tool kit includes treatment protocols, GP and patient information leaflets, a list of infection control measures, and contact details of ID physicians for specialized advice. A community-based (including nursing homes) prospective study was conducted in 2012 in Southeastern France to test the tool kit in the context of ESBL-E-related urinary tract infections (UTI). ESBL-E-related UTI were identified in 88 patients, 66 GPs were contacted by the microbiology laboratory, 56 stated they were offered the tool kit, 48 said they had received it, and 41 stated they had read its contents. Use of the tool kit was significantly correlated with appropriate antibiotic prescription, which concerned 36/39 tool kit users versus 13/20 non-users (p = 0.0125) and 40 GPs expressed an average satisfaction rate of 4.2 on a scale of 0 to 5. Availability of a specific tool for managing patients harboring ESBL-E, now completed with a website, can assist community-based GPs and improve antimicrobial prescription.
ClosePublications 2017 du Dr COURJON Johan
Efficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort studyEfficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort study
Efficacy and safety of clindamycin-based treatment for bone and joint infections: a cohort study
J Courjon, E Demonchy, E Cua, E Bernard, P-M Roger
https://pubmed.ncbi.nlm.nih.gov/28884303/
Abstract
Clindamycin has high bioavailability together with good diffusion in bone tissue and could represent an alternative antibiotic compound for the treatment of bone and joint infections (BJIs). However, data regarding the efficacy and safety of clindamycin for BJIs are limited. A monocentric cohort study based on our medical dashboard, which prospectively recorded 28 characteristics for all hospitalized patients since July 2005, was performed. BJIs were selected, and then, all mono-microbial BJI managed with clindamycin-based therapy were included. Remission was defined as the absence of clinical and/or microbiological relapse after treatment. The duration of follow-up without relapse was determined retrospectively using computerized medical records. For 10 years, 196 BJIs, of which 80 (41%) were device-associated infections, were treated with clindamycin-based therapy. The bacterial causative agent was Staphylococcus aureus in 130 cases (66%), coagulase-negative staphylococci in 29 cases (15%), streptococci in 31 cases (16%) and other bacteria in 6 cases (3%). When used in combination therapy, clindamycin was mainly paired with fluoroquinolones (31%) or rifampin (27%). The mean duration of clindamycin treatment was 7.4 ± 3.2 weeks (range, 1-24). An AE was recorded for 9 (4.5%) patients. Remission was recorded for 111 (57%) patients, with a mean duration of clinical follow-up of 28 ± 24 months. Treatment failure occurred in 22 (11%) patients, 50 patients (25%) were lost to follow-up, and 8 (4%) required long-term suppressive therapy. Among the assessable patients, clindamycin-based therapy was efficient in 111/133 cases (83%) and thus represents a reliable and safe alternative treatment option.
Keywords: Bone and joint infections; Clindamycin; Efficacy; Staphylococcus; Streptococcus; Tolerance.
ClosePatients with community-acquired bacteremia of unknown origin: clinical characteristics and usefulness of microbiological results for therapeutic issues: a single-center cohort studyPatients with community-acquired bacteremia of unknown origin: clinical characteristics and usefulness of microbiological results for therapeutic issues: a single-center cohort study
Johan Courjon, Elisa Demonchy, Nicolas Degand, Karine Risso, Raymond Ruimy, Pierre-Marie Roger
https://pubmed.ncbi.nlm.nih.gov/28526094/
Abstract
Bacteremia of unknown origin (BUO) are associated with increased mortality compared to those with identified sources. Microbiological data of those patients could help to characterize an appropriate empirical antibiotic treatment before bloodcultures results are available during sepsis of unknown origin. Based on the dashboard of our ward that prospectively records several parameters from each hospitalization, we report 101 community-acquired BUO selected among 1989 bacteremic patients from July 2005 to April 2016, BUO being defined by the absence of clinical and paraclinical infectious focus and no other microbiological samples retrieving the bacteria isolated from blood cultures. The in-hospital mortality rate was 9%. We retrospectively tested two antibiotic associations: amoxicillin-clavulanic acid + gentamicin (AMC/GM) and 3rd generation cephalosporin + gentamicin (3GC/GM) considered as active if the causative bacteria was susceptible to at least one of the two drugs. The mean age was 71 years with 67% of male, 31 (31%) were immunocompromised and 52 (51%) had severe sepsis. Eleven patients had polymicrobial infections. The leading bacterial species involved were Escherichia coli 25/115 (22%), group D Streptococci 12/115 (10%), viridans Streptococci 12/115 (10%) and Staphylococcus aureus 11/115 (9%). AMC/GM displayed a higher rate of effectiveness compared to 3GC/GM: 100/101 (99%) vs 94/101 (93%) (p = 0.04): one Enterococcus faecium strain impaired the first association, Bacteroides spp. and Enterococcus spp. the second. In case of community-acquired sepsis of unknown origin, AMC + GM should be considered.
Keywords: Antimicrobial resistance; Bacteremia; Bacteremia of unknown origin; Empirical antibiotic treatment; Primary bacteremia; Severe sepsis.
ClosePyogenic vertebral osteomyelitis of the elderly: Characteristics and outcomesPyogenic vertebral osteomyelitis of the elderly: Characteristics and outcomes
Pyogenic vertebral osteomyelitis of the elderly: Characteristics and outcomes
Johan Courjon, Adrien Lemaignen, Idir Ghout, Audrey Therby, Nadia Belmatoug, Aurélien Dinh, Guillaume Gras, Louis Bernard, DTS (Duration of Treatment for Spondylodiscitis) study group
https://pubmed.ncbi.nlm.nih.gov/29206837/
Abstract
Background: The incidence of pyogenic vertebral osteomyelitis (PVO) has increased over the past two decades. One possible cause of this increase is the aging of the population, which results in more comorbidities in high income countries.
Objective: To better characterize the clinical presentation and outcome of PVO in the elderly.
Design: We conducted a post-hoc analysis of a previously published trial that studied treatment duration in PVO and compared the presentation and outcomes according to age.
Participants: Our analysis included 351 patients among whom 85 (24%) were 75-years-old or more.
Results: There were no significant differences in the socio-demographics of the patients. Neoplasia and chronic inflammatory diseases were more common in the older group: 34% vs. 19% (p = 0.021) and 9% versus 1% (p = 0.004), respectively. There were no significant differences in clinical and radiological presentations between the groups in terms of back pain (337/351, 97%), fever (182/351, 52%), PVO localization, neurological signs and epidural abscess. Associated infective endocarditis (IE) was more frequent in the older group (37% vs. 14%, p<0.001). Streptococci were more frequently involved in infections of older patients (29% vs. 14%, p = 0.003) in contrast to Staphylococcus aureus (31% vs. 45%, p = 0.03). Older patients displayed higher mortality rates at 1 year (21% vs. 3%, p<0.001) and more adverse events related to cardiorespiratory failure (10.6% vs. 3.8%, p = 0.025), but had similar quality of life among the survivors.
Conclusion: During PVO, the clinical and radiological findings are similar in older patients. Global mortality rates are higher in older patients compared to younger patients, which could be explained by the increased frequency of neoplasia at diagnosis and higher prevalence of associated IE in the elderly.
ClosePublications 2015 du Dr COURJON Johan
Clinical Aspects of Syphilis Reinfection in HIV-Infected PatientsClinical Aspects of Syphilis Reinfection in HIV-Infected Patients
Clinical Aspects of Syphilis Reinfection in HIV-Infected Patients
Johan Courjon, Thomas Hubiche, Nicolas Dupin, Philippe Alain Grange, Pascal Del Giudice
https://pubmed.ncbi.nlm.nih.gov/25823442/
Abstract
Background: The incidence of HIV-syphilis co-infection has risen since 2000, especially among men having sex with men (MSM). Syphilis reinfection can occur, but the clinical features of such events remain poorly characterized.
Objective: To compare the cutaneous lesions seen with syphilis reinfections with those of first episodes in HIV-infected patients.
Methods: In a cohort of HIV-infected patients, syphilis reinfection was established both clinically and biologically by evaluating changes in Venereal Disease Research Laboratory titers. Photographs and medical records were studied in order to determine the type of skin lesions and their quantification.
Results: Among 533 HIV-infected patients, 42 (8%) experienced a first syphilis infection. Thirteen episodes of reinfection occurred in 12/42 (28%) patients, all MSM. In 78% of cases, reinfections were less symptomatic than first episodes. All patients presented classical syphilis lesions.
Conclusions: We observed a high rate of reinfection, but with less severe skin manifestations during reinfection episodes.
CloseEDIN-B Promotes the Translocation of Staphylococcus aureus to the Bloodstream in the Course of PneumoniaEDIN-B Promotes the Translocation of Staphylococcus aureus to the Bloodstream in the Course of Pneumonia
Johan Courjon, Patrick Munro, Yvonne Benito, Orane Visvikis, Coralie Bouchiat, Laurent Boyer, Anne Doye, Hubert Lepidi, Eric Ghigo, Jean-Philippe Lavigne, François Vandenesch, Emmanuel Lemichez
https://pubmed.ncbi.nlm.nih.gov/26501320/
Abstract
It is crucial to define risk factors that contribute to host invasion by Staphylococcus aureus. Here, we demonstrate that the chromosomally encoded EDIN-B isoform from S. aureus contributes to the onset of bacteremia during the course of pneumonia. Deletion of edinB in a European lineage community-acquired methicillin resistant S. aureus (CA-MRSA) strain (ST80-MRSA-IV) dramatically decreased the frequency and magnitude of bacteremia in mice suffering from pneumonia. This deletion had no effect on the bacterial burden in both blood circulation and lung tissues. Re-expression of wild-type EDIN-B, unlike the catalytically inactive mutant EDIN-R185E, restored the invasive characteristics of ST80-MRSA-IV.
Keywords: bacteremia; methicillin-resistant Staphylococcus aureus; toxins; virulence factor.
ClosePublications 2013 du Dr COURJON Johan
Antibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective studyAntibiotics-related adverse events in the infectious diseases department of a French teaching hospital: a prospective study
J Courjon, C Pulcini, E Cua, K Risso, F Guillouet, E Bernard, P-M Roger
https://pubmed.ncbi.nlm.nih.gov/23877571/
Abstract
Antibiotics are a significant cause of adverse events (AE), but few studies have focused on prescriptions in hospitalized patients. In infectious diseases departments, the high frequency and diversity of antibiotics prescribed makes AE post-marketing monitoring easier. The aim of our study was to assess the incidence and type of AE in the infectious diseases department of a French teaching tertiary-care hospital. The main characteristics of each hospitalization, including all antibiotics prescribed and any significant AE were recorded prospectively in the medical dashboard of the department. We included all patients having suffered an AE due to systemic antibiotics between January 2008 and March 2011. Among the 3963 hospitalized patients, 2682 (68%) received an antibiotic and 151/2682 (5.6%) suffered an AE. Fifty-two (34%) AE were gastrointestinal disorders, 32 (21%) dermatological, 20 (13%) hepatobiliary, 16 (11%) renal and urinary disorders, 13 (9%) neurological and 11 (7%) blood disorders. Rifampin, fosfomycin, cotrimoxazole and linezolid were the leading causes of AE. Sixty-two percent of the antibiotics causing an AE were stopped and 38% were continued (including 11% with a dose modification). Patients suffering from AE had an increased length of stay (18 vs 10 days, P < 0.001). Our data could help choosing the safest antibiotic when several options are possible.
CloseSkin findings of Staphylococcus aureus toxin-mediated infection in relation to toxin encoding genesSkin findings of Staphylococcus aureus toxin-mediated infection in relation to toxin encoding genes
Skin findings of Staphylococcus aureus toxin-mediated infection in relation to toxin encoding genes
Johan Courjon, Thomas Hubiche, Alice Phan, Anne Tristan, Michele Bès, François Vandenesch, Jerome Etienne, Pascal Del Giudice, Yves Gillet
https://pubmed.ncbi.nlm.nih.gov/23446443/
Abstract
Background: Staphylococcal scalded skin syndrome and toxic shock syndrome are associated with exfoliatins and superantigens, respectively; and are easy to distinguish in their usual presentation. However, there is confusion about the mild forms of these 2 staphylococcal diseases. These mild forms are both designated as « staphylococcal scarlet fever » despite differences in their pathophysiology and clinical presentation. Our study aimed to distinguish between the clinical characteristics of the rash associated with exfoliatins and the rash associated with superantigens.
Methods: Patients were selected from the French National Reference Center for Staphylococci. We retrospectively compared the clinical characteristics of patients with a generalized rash during Staphylococcus aureus infection. Patients who met the criteria of staphylococcal scalded skin syndrome or toxic shock syndrome were excluded. The patients were classified into 2 groups depending on the presence of a gene coding for exfoliatin or for superantigenic toxin.
Results: We included 13 cases with exfoliatin and 9 with superantigens. The patients of the exfoliatin group were more likely to have facial involvement, fold involvement and a superficial focus of infection. In the second group, S. aureus was isolated from a deeper focus in 8 of 9 patients.
Conclusion: Mild forms of S. aureus toxin-mediated infection affect the pediatric population. Examination made it possible to distinguish an exanthema associated with an exfoliatin from one associated with a superantigen. This early clinical distinction results in differences in management.
CloseTravaux originaux (français)
Medical table: A major tool for antimicrobial stewardship policyMedical table: A major tool for antimicrobial stewardship policy
Medical table: A major tool for antimicrobial stewardship policy
P-M Roger, E Demonchy, K Risso, J Courjon, S Leroux, E Leroux, É Cua
https://pubmed.ncbi.nlm.nih.gov/28457702/
Abstract
Infectious diseases are unpredictable, with heterogeneous clinical presentations, diverse pathogens, and various susceptibility rates to anti-infective agents. These features lead to a wide variety of clinical practices, which in turn strongly limits their evaluation. We have been using a medical table since 2005 to monitor the medical activity in our department. The observation of heterogeneous therapeutic practices led to drafting up our own antibiotic guidelines and to implementing a continuous evaluation of their observance and impact on morbidity and mortality associated with infectious diseases, including adverse effects of antibiotics, duration of hospital stay, use of intensive care, and deaths. The 10-year analysis of medical practices using the medical table is based on more than 10,000 hospitalizations. It shows simplified antibiotic therapies and a reduction in infection-related morbidity and mortality. The medical table is a major tool for antimicrobial stewardship, leading to constant benefits for patients.
Keywords: Antibiothérapie; Antibiotic therapy; Antimicrobial stewardship; Bacterial resistance; Bon usage des antibiotiques; Medical table; Résistance bactérienne; Tableau de bord.
Copyright © 2017 Elsevier Masson SAS. All rights reserved.
CloseThe impact of bacteremia on the outcome of bone infectionsThe impact of bacteremia on the outcome of bone infections
The impact of bacteremia on the outcome of bone infections
P-M Roger, E Cua, J Courjon, L Landraud, M Carles, E Bernard
https://pubmed.ncbi.nlm.nih.gov/25169941/
Abstract
We have used a medical database to analyze our activity since 2005. We observed a frequent association between bone and joint infection (BI) and bacteremia. Our aim was to characterize patients with BI and bacteremia, and focus on the outcome.
Patients and method: Our database includes the prospective recording of 28 characteristics of all hospitalized patients, including diagnosis, comorbid conditions, microbiological data, therapy, and outcome. We selected patients presenting with BI in this database, from July 2005 to December 2012. Fever before blood culture was retrospectively documented from the patient’s chart. Chronic BI was defined as a disease lasting more than 1 month. An unfavorable outcome was defined by the need for intensive care or death.
Results: Six hundred and thirty-two patients presented with BI and 125 with bacteremia (19.8%). We used a stepwise logistic regression analysis and determined that bacteremia was associated with vertebral osteomyelitis, OR, 3.97, P<0.001; alcohol abuse, OR, 2.51, P=0.010; fever, OR, 2.43, P<0.001; neurological and/or psychiatric diseases, OR, 2.41, P ≤ 0.001; and Staphylococcus aureus infection, OR, 2.32, P<0.001. The outcome was unfavorable in 23 cases (3.6%), associated with bacteremia, OR, 8.00, P<0.001, age> 60 years, OR, 4.78, P=0.018, and S. aureus infection, OR, 3.96, P=0.010. No single comorbid condition was significantly associated with an unfavorable outcome.
Conclusion: Bacteremia occurred in nearly 20% of the patients presenting with BI, and was associated with identifiable comorbid conditions; it was the main risk factor for an unfavorable outcome.
Keywords: Bacteremia; Bactériémie; Bone infection; Infection ostéoarticulaire; Outcome; Pronostic; Staphylococcus.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.
CloseTravaux originaux avec participation aux groupes d’étude
Repurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial ResultsRepurposed Antiviral Drugs for Covid-19 - Interim WHO Solidarity Trial Results
Repurposed Antiviral Drugs for Covid-19 – Interim WHO Solidarity Trial Results
WHO Solidarity Trial Consortium
https://pubmed.ncbi.nlm.nih.gov/33264556/
Abstract
Background: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs – remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a – in patients hospitalized with coronavirus disease 2019 (Covid-19).
Methods: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.
Results: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.
Conclusions: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).
Copyright © 2020 Massachusetts Medical Society.
CloseType 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO StudyType 1 Diabetes in People Hospitalized for COVID-19: New Insights From the CORONADO Study
CloseMissed opportunities of HIV pre-exposure prophylaxis in France: a retrospective analysis in the French DAT'AIDS cohortMissed opportunities of HIV pre-exposure prophylaxis in France: a retrospective analysis in the French DAT'AIDS cohort
DAT’AIDS STUDY GROUP
https://pubmed.ncbi.nlm.nih.gov/30909885/
Abstract
Background: HIV pre-exposure prophylaxis (PrEP) was implemented in France in November 2015 based on individual-level risk factors for HIV infection. We evaluated the proportion of missed opportunities for PrEP among newly HIV-diagnosed people entering the Dat’AIDS cohort in 2016.
Methods: Multicenter retrospective analysis in 15 French HIV clinical centers of patients with a new diagnosis of HIV infection. Among them we differentiated patients according to the estimated date of infection: those occurring in the PrEP area (a previous negative HIV test in the last 12 months or those with an incomplete HIV-1 western blot (WB) with no HIV-1 anti-Pol-antibody at time of HIV diagnosis) and those in the pre-PrEP area (older infections). Epidemiological, biological and clinical data at HIV diagnosis were collected. Clinicians retrospectively identified potential eligibility for PrEP based on individual-level risk factors for HIV infection among those infected in the PrEP area.
Results: Among 966 patients with a new HIV diagnosis, 225 (23.3%) were infected in the PrEP area and 121 (53.8%) had complete data allowing evaluation of PrEP eligibility. Among them, 110 (91%) would have been eligible for PrEP, median age 31 years, with 68 (75.6%) born in France and 10 (11.1%) in Central/West Africa, with more than one previous STI in 19 (15.7%). The main eligibility criteria for PrEP were being a man who had sex with men or transgender 91 (82.7%) with at least one of the following criteria: unprotected anal sex with ≥2 partners in the last 6 months: 67 (60.9%); bacterial sexually transmitted infection in the last 12 months: 33 (30%); Use of psychoactive substances in a sexual context (chemsex): 16 (14.5%). PrEP was indicated for other HIV risk factors in 25 (22.7%).
Conclusion: With 91% (110/121) of patients infected in the PrEP area eligible for PrEP, this study highlights the high potential of PrEP in avoiding new infection in France but also shows a persistent delay in HIV testing. Thus, an important limit on PrEP implementation in France could be insufficient screening and care access.
Keywords: HIV; HIV testing; Missed opportunities; PrEP; Pre-exposure prophylaxis.
CloseIntegrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohortIntegrase strand transfer inhibitors and neuropsychiatric adverse events in a large prospective cohort
Dat’AIDS Study Group
https://pubmed.ncbi.nlm.nih.gov/30534993/
Abstract
Objectives: To analyse the frequency and causes of treatment discontinuation in patients who were treated with an integrase strand transfer inhibitor (INSTI), with a focus on neuropsychiatric adverse events (NPAEs).
Methods: Patients in 18 HIV reference centres in France were prospectively included in the Dat’AIDS cohort. Data were collected from all patients starting an INSTI-containing regimen between 1 January 2006 and 31 December 2016. All causes of INSTI-containing regimen discontinuations were analysed, and patients’ characteristics related to discontinuation due to NPAEs were sought.
Results: INSTIs were prescribed to 21315 patients: 6274 received dolutegravir, 3421 received elvitegravir boosted by cobicistat, and 11620 received raltegravir. Discontinuation was observed in 12.5%, 20.2% and 50.9% of the dolutegravir-, elvitegravir- and raltegravir-treated patients, respectively (P < 0.001). Discontinuation for NPAEs occurred in 2.7%, 1.3% and 1.7% of the dolutegravir-, elvitegravir-, and raltegravir-treated patients, respectively (P < 0.001). In the multivariate analysis, discontinuation for NPAEs was related to dolutegravir versus elvitegravir (HR = 2.27; 95% CI 1.63-3.17; P < 0.0001) and versus raltegravir (HR = 2.46; 95% CI 2.00-3.40; P < 0.0001), but neither gender (HR for women = 1.19; 95% CI 0.97-1.46; P = 0.09) nor age (P = 0.12) was related. The association with abacavir was not retained in the final model.
Conclusions: Although discontinuation for side effects was less frequent with dolutegravir than with boosted elvitegravir, discontinuation for NPAEs, although rare (2.7%), was more frequent with dolutegravir. No patient characteristic was found to be associated with these side effects in this very large population.
© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.
CloseGender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D StudyGender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study
Data Collection of Adverse Events of Anti-HIV drugs (D:A:D) Study group
https://pubmed.ncbi.nlm.nih.gov/29509305/
Abstract
Introduction: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV-positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study.
Methods: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders.
Results: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti-hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow-up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti-hypertensives (1.17 [1.10, 1.25]).
Conclusion: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV-positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions.
Keywords: Cardiovascular disease; HIV; cardiovascular disease interventions; cohort studies; gender; myocardial infarction; stroke; women.
© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.
CloseDirect-acting antiviral treatment against hepatitis C virus infection in HIV-Infected patients - ``En route for eradication``?Direct-acting antiviral treatment against hepatitis C virus infection in HIV-Infected patients - ``En route for eradication``?
Dat’AIDS study Group
https://pubmed.ncbi.nlm.nih.gov/28579302/
Abstract
Objectives: Direct-Acting Antivirals (DAAs) opened a new era in HCV treatment. We report the impact of HCV treatment in French HIV-HCV coinfected patients.
Methods: All HIV-HCV patients from the Dat’AIDS cohort followed between 2012 and 2015 were included. HCV status was defined yearly as naive, spontaneous cure, sustained virological response (SVR12), failure or reinfection.
Results: Among 32,945 HIV-infected patients, 15.2% were positive for anti-HCV antibodies. From 2012 to 2015, HCV incidence rate increased from 0.35%PY to 0.69%PY in MSM, while median incidence was 0.08%PY in other patients. Median reinfection rate was 2.56%PY in MSM and 0.22%PY in other patients. HCV treatment initiation rate rose from 8.2% in 2012 to 29.6% (48.0% in pre-treated patients vs 22.6% in naïve patients). SVR12 rate increased from 68.7% to 95.2%. By the end of 2015, 62.7% of the patients were cured either spontaneously or following SVR.
Conclusions: HCV treatment dramatically increased in HIV-HCV patients in France from 2012 to 2015 resulting in HCV cure in nearly two-thirds of the patients in this cohort. Combined with a declining HCV prevalence, the prevalence of active HCV infection among HIV patients will drastically decrease in the forthcoming years.
Keywords: Coinfection; DAA; Direct acting antiviral agent; Epidemiology; HCV; HIV; Treatment uptake.
Copyright © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
CloseClinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort studyClinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study
MONALISA study group
https://pubmed.ncbi.nlm.nih.gov/28139432/
Abstract
Background: Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors.
Methods: MONALISA was a national prospective observational cohort study. We enrolled eligible cases declared to the National Reference Center for Listeria (all microbiologically proven) between Nov 3, 2009, and July 31, 2013, in the context of mandatory reporting. The outcomes were analysis of clinical features, characterisation of Listeria isolates, and determination of predictors of 3-month mortality or persisting impairment using logistic regression. A hierarchical clustering on principal components was also done for neurological and bacteraemic cases. The study is registered at ClinicalTrials.gov, number NCT01520597.
Findings: We enrolled 818 cases from 372 centres, including 107 maternal-neonatal infections, 427 cases of bacteraemia, and 252 cases of neurolisteriosis. Only five (5%) of 107 pregnant women had an uneventful outcome. 26 (24%) of 107 mothers experienced fetal loss, but never after 29 weeks of gestation or beyond 2 days of admission to hospital. Neurolisteriosis presented as meningoencephalitis in 212 (84%) of 252 patients; brainstem involvement was only reported in 42 (17%) of 252 patients. 3-month mortality was higher for bacteraemia than neurolisteriosis (hazard ratio [HR] 0·54 [95% CI 0·41-0·69], p<0·0001). For both bacteraemia and neurolisteriosis, the strongest mortality predictors were ongoing cancer (odds ratio [OR] 5·19 [95% CI 3·01-8·95], p<0·0001), multi-organ failure (OR 7·98 [4·32-14·72], p<0·0001), aggravation of any pre-existing organ dysfunction (OR 4·35 [2·79-6·81], p<0·0001), and monocytopenia (OR 3·70 [1·82-7·49], p=0·0003). Neurolisteriosis mortality was higher in blood-culture positive patients (OR 3·67 [1·60-8·40], p=0·002) or those receiving adjunctive dexamethasone (OR 4·58 [1·50-13·98], p=0·008).
Interpretation: The severity of listeriosis is higher than reported elsewhere. We found evidence of a significantly reduced survival in patients with neurolisteriosis treated with adjunctive dexamethasone, and also determined the time window for fetal losses. MONALISA provides important new data to improve management and predict outcome in listeriosis.
Funding: Programme Hospitalier Recherche Clinique, Institut Pasteur, Inserm, French Public Health Agency.
Copyright © 2017 Elsevier Ltd. All rights reserved.
CloseTravaux didactiques
Infections à VZV varicelle et zona / Infections à Herpès virus du sujet immunocompétentInfections à VZV varicelle et zona / Infections à Herpès virus du sujet immunocompétent
Infections à VZV varicelle et zona / Infections à Herpès virus du sujet immunocompétent
Courjon J, Demochy E, Roger P-M
La revue du praticien avril 2017, tome 67, numéro 4, e183-e188
CloseLeucoencéphalite multifocale progressive en hématologieLeucoencéphalite multifocale progressive en hématologie
Leucoencéphalite multifocale progressive en hématologie.
Risso K, Courjon J.
Correspondance en onco-hématologie. Vol 11 n°2 Mars 2016
Close -
Lettres, cas cliniques, éditorial
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Lettres à la rédaction, cas cliniques, éditorial (anglais)
Extended Antibiotic Treatment Duration after DAIRExtended Antibiotic Treatment Duration after DAIR
Extended Antibiotic Treatment Duration after DAIR
J Courjon, P Del Giudice
Clin Inf Dis 2020
CloseEpidemiology of human common coronavirus acquisition in pilgrimsEpidemiology of human common coronavirus acquisition in pilgrims
Epidemiology of human common coronavirus acquisition in pilgrims
Thi Loi Dao, Van Thuan Hoang, Tran Duc Anh Ly, Ndiaw Goumballa, Johan Courjon, Ziad Memish, Cheikh Sokhna, Didier Raoult, Philippe Parola, Philippe Gautret
CloseRe: 'Pathogenesis and management of fracture-related infection' by Depypere et alRe: 'Pathogenesis and management of fracture-related infection' by Depypere et al
Re: ‘Pathogenesis and management of fracture-related infection’ by Depypere et al
R Manuello, R Ruimy, P Boileau, C Trojani, J Courjon
CloseDirect-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challengeDirect-acting antiviral treatment in adults infected with hepatitis C virus: Reactivation of hepatitis B virus coinfection as a further challenge
Anne De Monte, Johan Courjon, Rodolphe Anty, Eric Cua, Alissa Naqvi, Véronique Mondain, Jacqueline Cottalorda, Laurence Ollier, Valérie Giordanengo
https://pubmed.ncbi.nlm.nih.gov/26967675/
Abstract
Use of direct-acting antiviral drugs (DAAs) greatly improves management of adults infected with hepatitis C virus (HCV) whether patients are treatment-naive or unsuccessfully pre-treated. Several inhibitors of viral nonstructural proteins (NS3/4A protease, NS5A and NS5B polymerase) allow a rapid HCV clearance and increase rates of sustained virological response. Both the EASL and AASLD guidelines have recently published up-to-date recommendations for their use, addressing each HCV genotype and particular situations. However, management of patients coinfected with hepatitis B virus (HBV) has been developed by these guidelines with reference to cases of HBV reactivation reported during previous anti-HCV regimens containing interferon known active against both HBV and HCV. In the setting of the interferon-free HCV therapies with DAAs only, the possibility of HBV reactivation during treatment of hepatitis C is raised due to viral interferences in HCV/HBV coinfected persons. Herein, we report a case of early HBV reactivation during DAAs-based anti-HCV treatment (ledipasvir/sofosbuvir) in a patient having a resolved HBV infection and chronically infected with HCV genotype 4 and HIV. Moreover, we review similar recent cases of HBV reactivation in patients infected with HBV and HCV genotype 1 during treatment of hepatitis C by regimen incorporating other combination of DAAs (sofosbuvir/simeprevir or daclatasvir/asunaprevir). Due to the potential risk of early HBV reactivation in HCV/HBV-coinfected patients during interferon-free DAAs-based HCV therapies, altogether these cases highlight the necessity to closely monitor HBV coinfection, regardless its stage (chronic, occult, resolved), whatever HCV genotype or class of DAAs used.
Keywords: HBV reactivation; HCV Direct-Acting Antivirals; HIV infection; NS3/4A protease inhibitors; NS5A inhibitors; NS5B polymerase inhibitors.
Copyright © 2016 Elsevier B.V. All rights reserved.
CloseSafety of antibiotics combinations against Staphylococcal bone and joint infectionsSafety of antibiotics combinations against Staphylococcal bone and joint infections
Safety of antibiotics combinations against Staphylococcal bone and joint infections
Agnès Danré, Johan Courjon, Evelyne Bernard, Eric Cua, Véronique Mondain, Pierre-Marie Roger
CloseLettres à la rédaction, cas cliniques, éditorial (français)
Erythematous skin nodules during treatment of Whipple's diseaseErythematous skin nodules during treatment of Whipple's disease
Erythematous skin nodules during treatment of Whipple’s disease
A Sanchez, P Del Giudice, C Mantion, S Mazellier, F Boukari, P-M Roger, J Courjon
https://pubmed.ncbi.nlm.nih.gov/33075401/
Keywords: Dermatology; Erythematous nodules; Immune reconstitution inflammatory syndrome; Infectious disease; Whipple disease.
CloseSevere intestinal obstruction due to Strongyloides stercoralis in a pregnant womanSevere intestinal obstruction due to Strongyloides stercoralis in a pregnant woman
Severe intestinal obstruction due to Strongyloides stercoralis in a pregnant woman
A Malézieux-Picard, M C Saint-Paul, J Dellamonica, J Courjon, N Tieulié, P Marty, J G Fuzibet, R Collomp, J A Marinho, V Queyrel
https://pubmed.ncbi.nlm.nih.gov/28651833/
Keywords: HTLV-1; Intestinal obstruction; Occlusion intestinale; Strongyloides stercoralis.
CloseAntimicrobial stewardship policy: time to revisit the strategy?Antimicrobial stewardship policy: time to revisit the strategy?
Antimicrobial stewardship policy: time to revisit the strategy?
P-M Roger, J Courjon, S Léotard, C Déchamp, N Négrin, M Vassallo; Network for Infectious Diseases Paca-Est
https://pubmed.ncbi.nlm.nih.gov/26387088/
Abstract
Recent data indicate that both the overall numbers of antibiotic prescription and the frequency of multidrug-resistant bacteria are increasing significantly. These threatening features are observed, despite national antimicrobial stewardship (AMS) policies aimed at decreasing antibiotic use. AMS should also focus on the initial steps leading to antibiotic prescription. Physicians and their patients should benefit from the structured clinical pathways, the latter being adapted to regional epidemiological data and resources. Continuous evaluation of these predefined clinical paths through a computerized medical dashboard will allow a critical review and finally the optimization of medical practices. These innovative behavioural approaches for clinicians will supply precise information on the relationship among the diagnosis, therapeutics and outcome. This changing environment will carry out the adapted therapeutic procedures, and appropriate antibiotic use will inherently improve.
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Communications orales
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Orateur invité
- Diagnostic d’une infection : 24/24 est-ce nécessaire. Journée nationale de formation des paramédicaux en infectiologie. JNI 2020
- Évaluation de la prise en charge des infections ostéo-articulaires complexes en France: audit national communication orale en plénière pour le congrès CRIOAC 2019
Hors invitation
- Perfusion continue de cloxacilline au cours des IOA à aureus RICAI 2018
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Brevets
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Brevets en lien avec les travaux menés au laboratoire Inserm sur l’inflammasome NLRP3 au cours des infections virales et bactériennes
EP193005502.7 (2019) “Methods and composition for treatment of NLRP3 inflammasome mediated IL-1beta dependent disorders”.
EP20315109.7 (2020) “Methods and compositions for treatment of SARS-CoV-2 infection”
EP20305782.3 (2020) “Methods and pharmaceutical composition for the treatment of infectious diseases »
EP20306245.0 (2020) “Methods for diagnosis and monitoring form of coronavirus infection”