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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.

Objectives The aim was to evaluate the feasibility and diagnostic contribution of protein profiling using matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) applied to sputum to diagnose pulmonary tuberculosis. Methods Sputum samples collected from patients suspected of having pulmonary tuberculosis were analysed using MALDI-TOF MS. Using the differentially expressed protein peaks, we compared three groups of patients, including those with confirmed pulmonary tuberculosis (PTB), those without tuberculosis but with a lower respiratory tract infection (non-TB LRTI) and those without tuberculosis and without an LRTI (non-TB controls). Results A total of 102 patients included 35 PTB, 36 non-TB LRTI and 31 non-TB controls. The model differentiated between the PTB patients and the non-TB controls using the 25 most differentially expressed protein peaks, with a sensitivity of 97%, 95% CI 85–100%, and a specificity of 77%, 95% CI 59–90%. The model distinguished the PTB patients from the non-TB LRTI patients using the ten most differentially expressed protein peaks, with a sensitivity of 80%, 95% CI 63–92%, and a specificity of 89%, 95% CI 74–97%. We observed that the negative predictive value of MALDI-TOF MS sputum analysis was higher (96%, 95% CI 80–100%) than that of direct sputum microscopic examination and sputum culture (78%, 95% CI 62–89%) for non-TB controls. When MALDI-TOF MS sputum analysis and direct microscopic examination were combined, the negative predictive value reached 94%, 95% CI 80–99%, for non-TB LRTI patients. Discussion These results suggest that MALDI-TOF MS sputum analysis coupled with microscopic examination could be used as a screening tool for diagnosing pulmonary TB.

Introduction Au cours de l’epidemie de COVID-19, un nombre inhabituel de cas d’engelures a ete rapporte en Europe. L’hypothese d’un lien entre ces engelures et la COVID a ete rapidement avancee. Cependant, aucune etude prospective explorant de facon approfondie ces cas d’engelure n’a ete realisee. Materiel et methodes Cette etude prospective monocentrique a ete realisee dans les unites COVID du CHU de Nice. Tous les patients consecutifs avec engelures vus entre le 26 mars et le 17 avril 2020 etaient inclus. Une evaluation multidisciplinaire etait realisee comprenant examen dermatologique, biopsie cutanee, explorations vasculaires, bilan biologique, PCR et serologie COVID-19. Un suivi des patients etait organise. ClinicalTrials.gov identifier : NCT04344119 . Resultats Quarante patients ont ete inclus (âge median 22 ans ; 12 a 67 ans) dont 21 femmes. Tous les patients presentaient un tableau clinique similaire d’engelures, parfois bulleuses ou necrotiques, interessant les orteils ou les mains et dans certains cas les chevilles et les talons. Un acrosyndrome etait present dans 47,5 % des cas. La notion de contact avec une personne ayant presente des symptomes grippaux ou la presence de signes infectieux chez le patient dans 6 semaines precedentes etait notee chez respectivement 60 % et 32 % des cas. Chez 2 familles, 2 personnes avaient eu des engelures de facon concomitante. La PCR SARS-CoV-2 etait negative chez tous les patients. La serologie COVID-19 etait positive chez 12 patients (IgA+ n = 7, IgG+ n = 3, IgM+ et IgG+ n = 1, IgG+ et IgA+ n = 1). Les D-dimeres etaient superieurs a 215 ng/mL dans 61,5 % des cas. Les biopsies realisees chez 19 patients montraient une image histologique compatible avec des lesions de lupus engelure/interferonopathie de type I associees a un epaississement des veinules par hyperplasie des cellules musculaires sous endotheliales correspondant a des pericytes. L’evaluation in vitro de la reponse interferon α etait significativement plus elevee chez les patients avec engelures par rapport aux patients avec des formes moderees a severes de COVID-19 (p Discussion Cette etude conforte l’hypothese d’un lien entre les cas d’engelures et le virus SARS-CoV-2. Elle suggere que les manifestations dermatologiques observees sont la consequence d’une reaction immune, de type interferonopathie reactionnelle de type 1, induite par l’infection et d’une microvasculopathie impliquant les pericytes.

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.

Introduction Les recommandations internationales proposent pour les patients hospitalises une β-lactammine + macrolide ou une fluoroquinolone (FQ). Dans un but de limitation de l’emergence de resistances, nous utilisons un protocole d’antibiotherapie probabiliste sans FQ ni cephalosporine de 3e generation (C3G). Le but de cette etude est d’etudier l’impact clinique de ce protocole et les facteurs associes a la concordance avec le protocole. Materiels et methodes Design : il s’agit d’une etude de cohorte observationnelle, monocentrique basee sur notre tableau de bord medical, renseigne prospectivement pour tous les patients hospitalises dans le service d’infectiologie incluant 28 parametres. Criteres d’inclusion : tous les patients hospitalises pour PAC ≥ 65 ans, entre 2008 et 2018. Protocole antibiotique : en traitement empirique, pour les PAC PSI III a V, une bitherapie AMX-CL + roxythromycine (RX) etait recommandee. Critere de jugement : la concordance etait definie par le respect du protocole pendant toute la duree du traitement antibiotique. Une evolution etait definie defavorable en cas de deces ou de transfert en reanimation. Resultats Caracteristiques de la population et facteurs associes a la concordance : parmi les 512 patients inclus, 340 etaient traites en concordance (C) avec le protocole et 172 etaient non-concordants (NC). Les caracteristiques etaient similaires pour l’âge (81,9 ans vs 81), PSI (114+ vs 117) et BPCO. La proportion de patients avec un cancer etait plus haute dans le groupe NC (20 %) vs groupe C (11 %) p = 0,0042. Microbiologie : 183 PAC (36 %) etaient documentees, S. pneumoniae etait le pathogene le plus frequemment mis en evidence. Une documentation a P. aeruginosa, S. aureus et Enterobacteriaceae etait significativement associee avec le groupe NC. En analyse multivariee, une antibiotherapie prealable, un cancer, une documentation par P. aeruginosa, S. aureus, et Enterobacteriaceae etaient des facteurs de risque de NC. Outcomes en fonction de la concordance : dans le groupe NC, il y avait plus d’evolution defavorable 32 (18,6 %) vs 28 (8,2 %) p = 0,0012, plus d’effets indesirables medicamenteux 13(8 %) vs 10(3 %) p = 0,02, une duree de sejour plus longue. Facteurs associes a une evolution defavorable : en analyse univariee, le PSI, la BPCO, une documentation a P. aeruginosa, et la non-concordance avec le protocole etaient associes a une evolution defavorable. En analyse multivariee, les facteurs de risque d’evolution defavorable etaient la BPCO : AOR 2,673 [1,363–5,240] p = 0,0042 ; le PSI moyen ; P. aeruginosa : AOR 3,866 [1,127–13,257] p = 0,032 ; et des hemocultures positives. Le seul facteur protecteur etait la concordance avec le protocole : AOR 0,448 [0,250–0,803], p = 0,007. Conclusion Cette etude montre que le respect de notre protocole etabli en excluant les fluoroquinolones et les C3G pour les pneumopathies du sujet âge est associe a une evolution favorable. Dans l’ere de l’antibioresistance le traitement des pneumopathies devrait se faire en evitant les C3G et les FQ, y compris chez le sujet âge.

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.

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.

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.

International audience; 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.

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.

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.

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.

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.

Introduction Les infections osteo-articulaires (IOA) constituent un ensemble d’infections heterogene reputees difficiles a traiter dont les modalites therapeutiques peuvent varier significativement : plusieurs aspects medicaux et chirurgicaux de la prise en charge de ces infections ne sont pas bien codifies. Nous avons realise grâce a un audit un etat des lieux national aupres des praticiens impliques. Materiels et methodes Durant le premier trimestre 2019, un questionnaire/mois a ete envoye aux professionnels de sante concernes par la prise en charge des IOA via la Societe Francaise de la Hanche et du Genou (SFHG), le Reseau National de Recherche Clinique en Infectiologie (RENARCI) et l’Association Francophone des Anesthesistes Reanimateurs en Chirurgie Orthopedique et Traumatologique (AFARCOT). Le premier cas clinique presentait un cas d’arthrite septique aigue sur articulation native du genou a S. aureus compliquee a un an d’une arthrose avec indication d’arthroplastie du genou. Il etait propose de repondre au questionnaire de maniere multidisciplinaire en RCP. Resultats Le premier questionnaire a recueilli 57 reponses (39 a titre individuel, 68 % ; 14 au cours d’une RCP, 29 %). La moitie des repondants exercait dans un centre labellise CRIOAc (49 %, 28/57). Devant une arthrite septique aigue sur articulation native, 88 % (46/52) des repondants proposent un geste chirurgical pour reduire l’inoculum bacterien, principalement par chirurgie avec synovectomie (69 %, 31/45). La totalite des repondants proposaient une antibiotherapie IV en post-operatoire immediat (32/32) pendant 3 a 5 jours (38 %, 12/32), ou 6 a 14 jours (59 %, 19/32). Lors du relais oral, la bitherapie etait privilegiee (84 %, 26/31), avec une combinaison associant rifampicine et quinolone (79 %, 23/29). La duree totale du traitement apres le lavage etait de quatre (23 %, 7/30) a six semaines (67 %, 20/30). Concernant la prise en charge de l’arthroplastie a distance, le geste privilegie etait une chirurgie en un temps (62 %, 31/50), et 26 % (13/50) guidaient le choix de l’option chirurgicale par une ponction articulaire pre-operatoire avec analyse bacteriologique et cytologique. Aucun des repondants ne choisissait une chirurgie en deux temps d’emblee. Enfin, 61 % des repondants (30/49) debutaient une antibiotherapie post-operatoire en attendant les resultats des nouveaux prelevements per-operatoires. Conclusion Cette premiere partie de l’etude montre que meme pour une entite classique comme l’arthrite septique a S. aureus, les pratiques medicales et chirurgicales sont tres heterogenes et que meme en l’absence de materiel etranger la bi-antibiotherapie incluant la rifampicine reste largement privilegiee.

Introduction La dalbavancine est un nouvel antibiotique a longue demi-vie, avec une activite anti bacteries cocci Gram positif. Son AMM concerne les infections de la peau et des tissus mous mais de nombreuses autres indications semblent interessantes. Nous avons etudie toutes les prescriptions de dalbavancine au cours des 19 premiers mois depuis sa mise sur le marche. Materiels et methodes Cohorte nationale retrospective (de juin 2017 a janvier 2019). Nous avons inclus tout patient ayant recu au moins une dose de dalbavancine, et collecte leurs caracteristiques, ainsi que l’indication et leur evolution. Resultats Au total, 70 patients dans 26 centres ont ete colliges. L’âge moyen etait de 63,2 ± 16,4 ans, et le sexe ratio (H/F) de 2,68 ; 24 (34,3 %) patients etaient immunodeprimes. Les indications etaient : infections osteoarticulaires (n = 45 ; 64,3 %), endocardites (n = 16 ; 22,9 %), infections cutanees/sous-cutanees (n = 12 ; 17,1 %), infections vasculaires (n = 5 ; 7,1 %), infections sur catheter (n = 4 ; 5,7 %), bacteriemie (n = 3 ; 5,0 %), et mediastinites (n = 2 ; 2,9 %). La dalbavancine etait utilise apres une mediane de 2,0 (IQR 1,0–3,0) lignes d’antibiotherapie. Les bacteries responsables ont ete identifiees dans 67 cas. Les principales bacteries retrouvees etaient : Staphylococcus aureus (n = 35 ; 52,2 %), y compris S. aureus resistant a la methicilline (n = 14 ; 20,9 %) ; Staphylococcus epidermidis (n = 22 ; 32,8 %), avec S. epidermidis resistant a la methicilline (n = 9 ; 15,8 %) ; autres staphylocoques coagulase-negative (n = 8 ; 11,9 %) ; Enterococcus faecalis (n = 4 ; 6,0 %). La dalbavancine etait prescrite en monotherapie dans 37 (52,9 %) cas. Les principaux schemas therapeutiques etaient : 2 doses de 1500 mg a une semaine d’intervalle dans 36 (51,4 %) cas, et une dose unique de 1500 mg dans 13 (18,6 %) cas. Mais, le nombre d’injections variaient de 1 a 10 doses (en moyenne 2,2 ± 1,5). En fin de traitement, le taux de guerison clinique etaient de 46 (76,7 %) patients, la mortalite toute cause etait de 2,9 %, avec un seul patient decede de cause septique. La guerison microbiologique etait presente dans 20/22 cas. Aucune souche resistante a la dalbavancine n’a ete retrouvee. A J 28 ou sortie d’hospitalisation, 53/67 patients etaient gueris, alors que 10 patients etaient en echec (recidive ou antibiotherapie suppressive). Seuls 5 evenements indesirables ont ete observes : lesions erythemateuses (n = 1), cephalees (n = 1), hypereosinophilie (n = 1), frissons et hyperthermie (n = 1), et placard inflammatoire (n = 1). Conclusion D’apres notre experience, la dalbavancine semble efficace et bien toleree dans les utilisations hors-AMM.

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.

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.

International audience; Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (

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.

Introduction Les medicaments sont d’autant plus prescrits qu’ils ont une reputation d’etre bien toleres. Il y a tres peu de donnees dans la litterature comparant les classes therapeutiques en pratique clinique. Nous avons compare les effets secondaires lies aux anti-infectieux a ceux lies aux autres classes therapeutiques en analysant leur impact sur la morbi-mortalite. Materiels et methodes Etude de cohorte monocentrique utilisant le tableau de bord d’hospitalisation d’un service d’Infectiologie de 34 lits. Ce dernier est renseigne pour chaque sejour par extraction de 28 parametres issus du compte rendu, incluant donnees demographiques, comorbidites definies par leurs traitements, diagnostic et agent pathogene en cause, anti-infectieux prescrits et leurs effets secondaires definis par la necessite d’un changement therapeutique, les evenements indesirables observes dont les effets secondaires des autres therapeutiques. La morbi-mortalite etait evaluee par la duree de sejour, le recours a la reanimation et la survenue du deces. Resultats Au total, 14 642 sejours etaient analyses de janvier 2006 a decembre 2017 ; moyenne d’âge 61 ± 20 ans, sex-ratio H/F 1,50. Un total de 1917 sejours (13 %) concernait des patients sans comorbidite traitee. Les 2 principales comorbidites etaient cardiaques (39 %) et pulmonaires (23 %). Un total de 10 294 sejours (70 %) beneficiaient de la prescription d’un anti-infectieux, menant a l’observation de 1007 effets secondaires (9,78 %). Les 2 molecules antibiotiques les plus frequemment en cause etaient la rifampicine (170 cas) et le cotrimoxazole (96 cas). Le total des effets secondaires des autres therapeutiques etait de 688 (4,69 %). Les plus frequemment en cause etaient les therapeutiques des comorbidites cardiaques (350 cas) et les antalgiques (127 cas). La duree moyenne de sejour etait de 8,9 ± 7,5 jours, de 16,4 ± 13,6 en cas d’effet secondaire d’un anti-infectieux et de 12,8 ± 10,5 en cas d’effet secondaire d’une autre therapeutique (p Conclusion En infectiologie, les effets secondaires lies aux anti-infectieux sont plus frequents que ceux lies aux autres therapeutiques. La morbidite associee implique leur prevention par les choix therapeutiques.

Introduction Du fait de notre organisation du systeme de sante, les premiers soins pour infections severes sont le plus souvent mis en œuvre dans les services d’urgence. Les bacteriemies sont usuellement associees a un sepsis severe. Ces 20 dernieres annees, l’emergence des bacteries multi-resistantes (BMR), y compris dans les infections communautaires, impliquent de determiner la meilleure antibiotherapie probabiliste, notamment lorsque le diagnostic est incertain. Notre objectif etait de determine quelle pourrait etre cette antibiotherapie probabiliste le plus souvent efficace pour une bacteriemie communautaire (BC), considerant qu’en cas d’incertitude, la plupart des prescripteurs proposerait une association d’antibiotiques (A-ATB). Materiels et methodes Etude retrospective monocentrique basee sur l’utilisation d’un tableau de bord d’hospitalisation utilise depuis juillet 2005. Tous les patients ayant presente une bacteriemie au cours d’une infection communautaire etaient inclus jusqu’a juin 2016. Ce tableau de bord inclus 28 parametres de chaque patient hospitalise, incluant les diagnostics, les comorbidites, les donnees microbiologiques, la distinction entre infections communautaires et infections associees aux soins, l’antibiotherapie instituee et l’evolution. Deux A-ATB etaient evaluees comme traitement probabiliste de ces BC : amoxicilline–ac. clavulanique (AMX-C) + gentamicine (G) versus cefotaxime (CTX) + gentamicine. Resultats Mille trois cent trente-cinq BC survenant chez 1203 patients etaient identifiees en 11 ans : moyenne d’âge 67 ± 18 ans, sex-ratio (H/F) 1,59. Un cancer et/ou une immunodepression etait observe dans 164 cas (12 %). Les 4 principaux groupes homogenes de maladies etaient les infections urinaires (n = 388, 29 %), les bacteriemies sans porte d’entree retrouvee (n = 228, 17 %) et les endocardites (n = 195, 15 %) et les infections osteoarticulaires (n = 148, 11 %). The 5 principales bacteries isolees etaient les enterobacteries (n = 492, 37 %, among which 413 E. coli infections, and 61 ESBL positive strains), Streptococcus (n = 305, 23 % including S. pneumoniae in 95 cases), Staphylococcus (n = 263, 20 %), polymicrobial bacteremia (n = 129, 10 %) and Enterococcus sp (n = 44, 3 %). Ces bacteries etaient globalement resistantes a AMX-C dans 22 % des cas, a CTX dans 32 % des cas. L’A-ATB AMX-C + G etait inefficace dans 1,4 % des cas comparativement a CTX + G inefficace dans 12,1 % of the cases. Le taux de deces etait de 5,8 %. Conclusion Face a un patient presentant un sepsis d’etiologie indetermine, AMX-C + G serait plus souvent efficace pour le traitement d’une bacteriemie communautaire que CTX + G.

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.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.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, P0.001; alcohol abuse, OR, 2.51, P=0.010; fever, OR, 2.43, P0.001; neurological and/or psychiatric diseases, OR, 2.41, P ≤ 0.001; and Staphylococcus aureus infection, OR, 2.32, P0.001. The outcome was unfavorable in 23 cases (3.6%), associated with bacteremia, OR, 8.00, P0.001, age60 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.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.

Revue du rhumatisme - In Press.Proof corrected by the author Available online since samedi 24 janvier 2015

Joint Bone Spine - In Press.Proof corrected by the author Available online since dimanche 22 juin 2014

Introduction – objectifs Au cours des infections osteo-articulaires (IOA) a staphylocoques une bi-antibiotherapie est recommandee. Les lincosamides et les fluoroquinolones sont des antistaphylococciques a bonne diffusion osseuse pouvant etre administres per os. L’efficacite de l’association de ces deux molecules est mal connue et merite d’etre mieux documentee pour justifier son utilisation. Materiels et methodes Les patients pris en charge pour IOA dans notre centre sont inclus dans une base de donnees specifique dans laquelle tous les antibiotiques prescrits ainsi que les effets indesirables (EI) associes sont references. Nous avons selectionne entre 2007 et 2013 les patients ayant recu l’association clindamycine + fluoroquinolone (C + F) pour une IOA a staphylocoque. L’efficacite therapeutique a ete determinee retrospectivement lorsque l’association C + F avait ete prescrite durant au moins la moitie de la duree d’antibiotherapie programmee. Resultats Les etapes de selection permettaient d’identifier 47 patients : 16 spondylodiscites (34 %), 13 IOA sur materiel (28 %), 11 arthrites (23 %) et 7 osteites (15 %). S. aureus et les staphylocoques a coagulase negative etaient impliques dans respectivement 78 % et 22 % des cas. Les F utilisees etaient la levofloxacine (60 %), l’ofloxacine (36 %) et la pefloxacine (4 %). La duree d’antibiotherapie etait de 48 jours en moyenne ; 7 patients (15 %) presentaient un EI imposant l’arret du traitement : 3 lies aux F et 4 lies a la C. Aucune diarrhee a C. difficile n’etait enregistree. L’association F + C avait ete administree durant 79 % de la duree totale d’antibiotherapie. Avec un recul median post-antibiotherapie de 26 mois, la guerison etait observee dans 87,5 % des cas, un echec dans 7,5 % des cas, 5 % des patients etant perdu de vue. Conclusion Au cours des IOA a staphylocoques l’association antibiotique F + C apparait efficace et bien toleree.

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.

Introduction : Prosthetic and joint infections (PJI) are among the most serious complications of joint replacements. In France, the management of these infections is organized around reference centers, CRIOACs. Our main objective was to carry out an audit, through a questionnaire survey organized around clinical cases, to evaluate the management of PJI by health professionals.Methods : The eligible participants were all health professionals involved in the management of PJI, who were registered on the list mailings dedicated to the management of these infections. Physicians could respond individually, or during multidisciplinary meeting dedicated to PJI. The survey consisted of three questionnaires, for a total of six clinical cases.Results : The response rate from CRIAOCs to the three questionnaires was 92%, 77%, and 53%. For a patient with a late infection, whose pre-operative puncture was positive for S. aureus, 39% did not administer antibiotic prophylaxis, with a difference between CRIAOCs (26%) and other centers (67%), p = 0.023. For surgical management, a large majority of respondents chose a one-time strategy. Rifampicin was used in one patient with S. aureus PJI (90-92%). The total duration of antibiotics was varied, ranging from six to 12 weeks.Conclusion : Surgical management in our investigation was fairly homogeneous, with a preference for surgery in one time. Medical management was more heterogeneous.; Introduction : les infections ostéo-articulaires (IOA) sont parmi les complications les plus sévères des arthroplasties. En France, la prise en charge de ces infections est organisée autour de centres de référence, les CRIOACs. Notre objectif principal était de réaliser un audit, grâce à une enquête par questionnaire organisé autour de cas cliniques, pour évaluer la prise en charge des IOA par les professionnels de santé concernés.Méthodes : les participants éligibles étaient tous les professionnels de santé impliqués dans la prise en charge des IOA, qui étaient inscrits sur les mailings liste dédiées à la prise en charge de ces infections. Les médecins pouvaient répondre individuellement, ou lors de RCP dédiées aux IOA. L’enquête consistait en trois questionnaires, soit un total de six cas cliniques. Résultats : le taux de réponses de la part des CRIAOCs aux trois questionnaires étaient de 92%, 77%, et 53%. Pour un patient avec une infection tardive, dont la ponction pré-opératoire est positive à S. aureus, 39% n’administrait pas d’antibioprophylaxie, avec une différence entre les CRIAOCs (26%) et les autres centres (67%), p=0,023. Pour la prise en charge chirurgicale, une large majorité des répondants choisissait une stratégie en un temps. La rifampicine était utilisée chez un patient présentent une IOA à S. aureus (90-92%). La durée totale d’antibiotiques était variée, allant de six à 12 semaines.Conclusion : la prise en charge chirurgicale dans notre enquête était assez homogène, avec une préférence pour la chirurgie en un temps. La prise en charge médicale était plus hétérogène.

Introduction : The time-dependant antibiotic cloxacillin is the gold standard treatment for the early phase of methicillin-susceptible Staphylococcus aureus bone and joint infections (BJI). Continuous infusion of some β-lactams is associated with pharmacokinetic/pharmacodynamic parameters improvement and more data are required to allow the extended use of cloxacilline through continuous infusion. We aimed to compare continuous and intermittent infusion of cloxacillin using in vivo pharmacology endpoints in patients presenting methicillin-susceptible S. aureus BJI.Methods : We conducted a prospective open-label trial to compare plasma concentrations of cloxacillin in each patient with either two 12-hour perfusions of 75 mg/kg per day (continuous period) or with four one-hour perfusions of 37,5 mg/kg daily (intermittent period). Pharmacologic assays were performed at H1, H2, H3, H4 and H6 during intermittent period and at H1, H6 and H11 during continuous period. Free drug concentration was considered for the analysis. We also assessed the patient’s comfort and the nurses’ preference for each period. Free drug concentration was considered for the analysis.Results : Eleven patients were analyzed. Among seven patients with all data available, 70% f T>MIC was achieved for 100% during continuous period and 86% during intermittent period (p>0,999). 100% f T>MIC was achieved for 100% during continuous period and 29% during intermittent period (p=0,021). No specific side effect of continuous infusion was detected. Continuous infusion was preferred to intermittent by four out of nine patients (44,4%) and 12 nurses out of 20 (60%).Conclusion : Continuous infusion provides higher plasmatic cloxacillin levels without specific side-effects. These results could allow its use in home-based care.; Introduction : la cloxacilline, antibiotique temps-dépendant, est l’antibiotique de référence dans le traitement initial des infections ostéo-articulaires (IOA) à Staphylococcus aureus sensible à la méticilline (SASM). L’administration continue (AC) de certaines β-lactamines est associée à une amélioration des paramètres pharmacocinétiques et pharmacodynamiques, mais les données sont manquantes concernant la cloxacilline. Nous avons comparé l’AC et l’administration intermittente (AI) de cloxacilline chez des patients avec IOA à SASM.Méthodes : nous avons mené un essai prospectif en ouvert comparant les concentrations de cloxacilline pour chaque patient entre deux perfusions de 75 mg/kg sur 12h (AC) et quatre perfusions de 37,5 mg/kg sur une heure, quatre fois par jour (AI). Les dosages pharmacologiques ont été réalisés à H1, H2, H3, H4 et H6 pendant l’AI et H1, H6, H11 pendant l’AC. Les concentrations libres ont été étudiées pour l’analyse. Le confort du patient et la préférence des infirmières pour chaque période ont été évalués.Résultats : 11 patients ont été analysés. Sur 7 patients ayant toutes les données, l’objectif 70% f T>MIC était atteint pour 100% des patients pendant l’AC et 86% pendant l’AI (p>0,999). 100% f T>MIC était atteint pour 100% des patients durant l’AC et 29 pendant l’AI (p=0,021). Il n’y avait pas d’effet indésirable spécifique à l’AC. l’AC était préférée par quatre patients sur neuf (44,4%) et 12 infirmières sur 20 (60%).Conclusion : l’AC permet d’obtenir des concentrations plasmatiques de cloxacilline plus élevées sans effet indésirable spécifique. Ces résultats pourraient permettre son utilisation à domicile.