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Clostridioides difficile infection (CDI) is a disease with high morbidity and mortality rates. The objective of this study was to describe CDI epidemiology and patient characteristics over a 5-year period in Switzerland and assess risk factors for mortality, recurrence and severe CDI.We retrospectively included all consecutive CDI cases having occurred in adult patients hospitalized in two tertiary centers: the Lausanne University Hospital (1000 beds) and the University Hospital of Zurich (900 beds), between 2014 and 2018. Suspected cases of CDI were identified from the microbiology laboratory database on the basis of a positive test and confirmed by records review.During first CDI episodes, the median age was 67 years and the median Charlson comorbidity index (CCI) score was 5. All in all, 299 out of 826 patients (36.2%) had severe infection based on the Infectious Diseases Society of America criteria. In the multivariable analysis, CCI was associated with increased risk of mortality. None of the factors recorded on admission were significantly associated with increased risk of recurrence. In the multivariable analysis, male sex and CCI were associated with severity, while immunosuppression was associated with less severe presentation.If we did not identify any criteria on admission that could be predictive of recurrences, this could be explained the retrospective nature of the study. A higher comorbidity index is a key driver for severe CDI and mortality. Reporting of CDI is not mandatory in Switzerland; structuration of CDI reporting should be a short-term priority.

While NLRC4-dependent sensing of intracellular Gram-negative pathogens such as Salmonella enterica serovar typhimurium is a beneficial host response, NLRC4-dependent sensing of the Pseudomonas aeruginosa type 3 secretion system (T3SS) has been shown to be involved in pathogenicity. In mice, different pathogen-associated microbial patterns are sensed by the combination of the NLRC4-inflammasome with different neuronal apoptosis inhibitory proteins (NAIPs). NAIP2 is involved in sensing PscI, an inner-rod protein of the P. aeruginosa T3SS. Surprisingly, only a single human NAIP (hNAIP) has been found. Moreover, there is no description of hNAIP-NLRC4 inflammasome recognition of T3SS inner-rod proteins in humans. Here, we show that the P. aeruginosa T3SS inner-rod protein PscI and needle protein PscF are both sensed by the hNAIP-NLRC4 inflammasome in human macrophages and PBMCs from healthy donors, allowing caspase-1 and IL-1β maturation and resulting in a robust inflammatory response. TLR4 and TLR2 are involved in redundantly sensing these two T3SS components.

Background Vascular thromboembolism (VTE) complicating cytomegalovirus (CMV) primary infection is increasingly reported in immunocompetent adults. No guideline is, however, currently available for the management of these infections and particularly for the antiviral therapy indication. Methods We performed a literature review of VTE complicating CMV primary infection in immunocompetent adults using PubMed. Results Sixty-nine case patients of VTE complicating CMV primary infection were reported. The main sites of venous thrombosis were the splanchnic veins (30 patients) or those of the lower limbs (18 patients). One-third of patients presented with pulmonary embolism (25 patients). Forty-nine patients (76%) had at least one VTE risk factor, inherited or acquired thrombophilia for 37 patients (58%), and another risk factor for 27 patients (42%). Only 11 patients received an antiviral therapy. A positive outcome was observed in all patients. Conclusion We suggest that antiviral therapy should be considered for patients presenting with severe VTE, VTE with a negative outcome despite anticoagulation, severe organ involvement, or for patients managed in the intensive care unit.

Introduction L’endocardite infectieuse est associee a un important risque d’embolisation, notamment au niveau cerebral. Le but de cette etude est de determiner les facteurs de risque d’embolisation cerebrale. Materiels et methodes Cette etude observationnelle prospective est effectue dans un hopital universitaire. Tous les patients avec suspicion d’endocardite ont ete inclus sur une duree de deux ans (de janvier 2018 a decembre 2019). L’endocardite infectieuse (prouvee et probable) est definie selon les criteres proposes par les recommandations de la Societe europeenne de cardiologie du 2015. Resultats Sur les 515 patients inclus, 105 ont eu un diagnostic d’endocardite prouvee et 34 d’endocardite probable (total = 139). Parmi eux, 124 (89,2 %) ont ete bacteriemiques, dont 47 a Staphylococcus aureus, 43 a streptocoques et 20 a enterocoques. Une embolisation systemique a ete retrouvee chez 70 patients (50,4 %), et la localisation cerebrale etait la plus frequente avec 44 patients. L’embolisation cerebrale etait plus frequente dans les situations d’endocardite mitrale (47,7 % vs 20,0 % ; p 0,001), d’endocardite sur prothese mecanique (38,6 % vs 15,8 % ; p 0,005), de vegetation du cœur gauche ≥ 10 mm (47,7 % vs 20,0 % ; p 0,001), d’embolisations spleniques (22,7 % vs 2,1 % ; p 0,001), et d’embolisation des membres (31,8 % vs 12,6 % ; p 0,010). Ni la presence d’une bacteriemie, le type de germe, la severite de l’infection, la presence de phenomenes immunologiques, ou les comorbidites n’ont ete associes a l’embolisation cerebrale. En analyse multivariee, seules la mise en evidence de vegetations du cœur gauche ≥ 10 mm (p 0,001 ; OR : 1,1, IC : 1,1–1,2) et l’embolisation des membres (p 0,035 ; OR : 12,7, IC : 1,2–33,9) ont ete independamment associees a l’embolisation cerebrale. Conclusion L’embolisation cerebrale est une complication frequente de l’endocardite infectieuse. La presence d’une grande vegetation (≥ 10 mm) et l’embolisation des membres sont independamment associees a presence des emboles cerebrales.

Introduction Les patients immunosupprimes (IS) presentent une incidence elevee d’infection a Clostridioides difficile (ICD) et un risque accru d’infection severe et de recurrences. Les donnees prospectives pour cette population sont rares. Nous avons compare le traitement et l’evolution de patients IS par rapport a des patients immunocompetents (IC). Materiels et methodes Cette etude prospective observationnelle a inclus tous les cas consecutifs d’ICD chez des adultes entre decembre 2018 et novembre 2019 dans un hopital universitaire. L’ICD a ete definie par la presence des diarrhees ou d’ileus avec un test positif pour C. difficile. Les tests utilises etaient une polymerase chain reaction (PCR) Xpert C. difficile (Cepheid Xpert® C. difficile BT) suivi d’un test immunochromatographique (C.DIFF QUIK CHEK COMPLETE® enzyme immunoassay, Labolife). La recurrence etait definie comme un nouvel episode dans les 8 semaines suivantes l’episode initial. Les criteres de severite ont ete definis selon les recommandations ESCMID (2014) et IDSA (2018). L’immunosuppression etait definie par la presence d’un des facteurs suivants : pathologie maligne hemato-oncologique ou d’organe solide active, transplantation d’organe solide ou de mœlle osseuse, infection VIH en stade SIDA, chimiotherapie active ou traitement immunosuppresseur. L’analyse statistique a ete realisee selon le test exact de Fischer (two-tailed) et un p Resultats Parmi les 87 cas inclus, au moins un facteur d’immunosuppression etait present dans 43 cas (49 %) et > 1 facteur dans 4 cas. Une pathologie maligne hematologique etait presente dans 18 cas, une tumeur solide dans 20 cas, une transplantation d’organe solide dans 3 cas, et un autre facteur d’immunosuppression dans 18 cas. Les recurrences etaient plus frequentes dans le groupe IS (10/43, 23,3 %) par rapport aux immunocompetents (5/44, 11,4 %) mais ceci n’etait pas statistiquement significatif (p 0,16). Au moins un critere de severite (selon IDSA et ESCMID) etait present pour 40 episodes (sur 56 episodes au total, comprenant 1ers episodes et recurrences, 71,4 %) chez les IS par rapport a 29 sur 50 (58 %) chez les IC, mais ceci n’etait pas statistiquement significatif. Enfin, la fidaxomicine etait plus frequemment administree en cas de premier episode chez les patients IS (17 sur 51 par rapport a 5 sur 50, p 0,007). Conclusion Meme si les recurrences et les infections severes etaient plus frequentes en chiffre dans le groupe des IS, ceci n’etait pas statistiquement significatif dans notre etude, probablement du au petit nombre des cas. La fidaxomicine est un traitement qui diminue le risque des recurrences mais coute plus cher. Ce traitement etait plus frequemment administre au groupe des IS qui semble constituer un groupe cible raisonnable pour une utilisation rationalisee de la molecule.

Résumé La dernière décennie a été marquée par l’incidence croissante des infections émergentes avec, pour principale conséquence, la nécessité de faire évoluer notre pratique et notre système de santé pour s’y adapter. Cette revue rassemble les principales crises auxquelles nous avons été confrontés ces dix dernières années avec une emphase particulière sur Ebola et les conséquences sur notre politique de prise en charge.

Clostridium difficile est devenu, en l’espace d’une dizaine d’annees, un enteropathogene de toute premiere importance, en raison de l’evolution des infections qui sont devenues plus frequentes, plus severes et plus difficiles a traiter. Pour tenir compte des avancees therapeutiques recentes, les recommandations europeennes pour le traitement des infections a C. difficile (ICD) ont ete actualisees en 2013. Le metronidazole (MTZ) [500 mg × 3/j, 10 jours] per os reste toujours la molecule de choix pour le traitement des formes peu a moderement severes d’ICD. Pour les formes severes, la vancomycine (VA) [125 mg × 4/j, 10 jours] per os est toujours preconisee, et la fidaxomicine (FDX) [200 mg × 2/j, 10 jours] represente une alternative a la VA. La chirurgie (colectomie) doit etre envisagee en cas de complications (megacolon ou choc septique). Le traitement de la premiere recidive ou des patients a risque de recidive repose principalement sur l’utilisation de la VA (125 mg × 4/j, 10 jours) ou de la FDX (200 mg × 2/j, 10 jours). La transplantation fecale devient le traitement de premiere intention des recurrences multiples (grade A-I). Les doses degressives et intermittentes de VA ou l’utilisation de FDX sont des alternatives (grade B-II).

Les enjeux energetiques du Syndicat des eaux d’Ilede-France (Sedif), premier service public d’eau potable en France, sont particulierement importants, puisque ses ouvrages de production et de distribution d’eau potable, specialement le pompage, consomment l’equivalent electrique d’une ville de 25 000 habitants (200 GWh par an environ). Cette consommation genere annuellement 15 700 tonnes en equivalent CO2. Par ailleurs, le territoire du Sedif presente de nombreux sites de fort potentiel de production d’energie renouvelable : 21 photovoltaiques, quatre eoliens, 15 geothermiques et 10 proches d’un reseau de chaleur.Afin de repondre a ces enjeux, la collectivite souhaite integrer dans sa politique energetique les objectifs europeens de diminuer de 20% les rejets de gaz a effet de serre (GES), d’augmenter de 20% l’efficacite energetique et de porter a 20% de la consommation globale la part des energies renouvelables d’ici 2020. Pour cela, le syndicat a decline ces objectifs, d’une part, dans le perimetre de sa maitrise d’ouvrage et, d’autre part, dans celui de l’exploitation deleguee a Veolia Eau d’Ile-de-France SNC.La consommation energetique de 20 sites, objets de travaux de renovation entre 2011 et 2015, sera mieux maitrisee par l’installation de moteurs ou de transformateurs a haut rendement et le remplacement de destructeurs thermiques d’ozone. Cinq projets pilotes pour produire ou utiliser de l’energie renouvelable ont ete etudies des 2010 : la mise en oeuvre d’installations de production d’energie photovoltaique sur les toitures des usines principales, l’installation de panneaux photovoltaiques sur les reservoirs de Châtillon et sur le nouveau reservoir de Villejuif, la mise en place d’une eolienne sur le nouveau reservoir de Palaiseau, et la substitution des moyens de chauffage dans l’usine de production de Choisy-le-Roi.Les leviers d’amelioration restants sont ceux que le Sedif impose a son delegataire Veolia Eau d’Ile-de-France SNC, dans le cadre du nouveau contrat d’une duree de 12 ans (a partir du 1er janvier 2011).

Objectives Adults with hematological malignancies are at high-risk of Clostridium difficile infection (CDI), but no guidelines for CDI treatment are available in this population. Our primary objective was to evaluate the clinical outcomes in CDI patients with hematological malignancies. Our secondary objectives were to describe CDI severity using the main clinical guidelines and to evaluate the compliance of treatment choice with published guidelines. Patients and methods Single-center, retrospective, observational case series including every consecutive adult patient with a confirmed diagnosis of CDI admitted in the hematology unit of our teaching hospital. Each CDI episode was classified as moderate, severe, or complicated according to the main clinical guidelines (IDSA 2010, AJG 2013, ESCMID 2014). Results Twenty-three episodes of CDI in 19 patients admitted to the hematology unit occurred between June 2012 and October 2013. Clinical cure was achieved for 20 episodes (87%). Ten weeks after diagnosis, global cure was reached for 14 episodes (61%) whereas recurrence occurred in two episodes (10%). The mortality rate reached 37% (7/19) but the attributable mortality rate was 5% (1/19). ESCMID criteria more frequently classified patients in the severe category compared with the two other classifications. Prescription compliance with clinical guidelines was observed in 61% of episodes with IDSA criteria, 43% with AJG, and 9% with ESCMID. Conclusions IDSA and AJG assessment may underestimate the potential risk of unfavorable clinical outcome. Further prospective studies on a larger cohort are needed to develop adequate treatment guidelines for CDI in hematology settings.

Tularaemia is an emerging anthropozoonosis transmitted by contact with infected animals and through arthropod bites, inhalation, or ingestion. We describe a pulmonary nodule suggesting cancer in a 70-year-old man. Histological analysis excluded neoplasia, and bacteriological culture excluded tuberculosis. Serological testing and PCR Francisella were positive for this hunter patient, then treated by ciprofloxacin with a favourable outcome.

Resume Pseudomonas aeruginosa est un bacille a Gram-negatif, responsable d’infections bronchopulmonaires chroniques. Il synthetise de nombreux facteurs de virulence dont l’expression est coordonnee par plusieurs systemes de regulation genique, dont l’interaction et l’intervention sequentielle lors d’une infection pulmonaire sont encore peu etablies. Objectif Le but de notre etude etait d’analyser l’evolution de l’expression pulmonaire de trois genes de virulence de P. aeruginosa (exoS, lasI et algD) appartenant a des systemes de regulation differents les sept premiers jours de l’infection. Des souris C57BL/6 ont ainsi ete instillees par un inoculum de P. aeruginosa inclut dans des billes d’agarose. Resultats Nos resultats montrent une diminution progressive de l’expression du gene exoS et une augmentation de l’expression des genes algD et lasI durant l’infection. Cette evolution dynamique corrobore les observations cliniques demontrant que les souches de P. aeruginosa isolees de patients atteints de la mucoviscidose presentent une perte progressive de la fonctionnalite du systeme de secretion de type III et un developpement de phenotype mucoide avec production d’alginate. Conclusion L’installation d’une infection chronique pulmonaire a P. aeruginosa associe une diminution de l’expression des genes associes au systeme de secretion de type III et une augmentation de la production d’alginate.

Several studies evidenced a pathogenic interaction between P. aeruginosa and C. albicans. P. aeruginosa is one of the most frequent microorganisms responsible for ventilator-associated pneumonia (VAP) and C. albicans usually colonize tracheo-bronchial tract of patients undergoing mechanical ventilation in the intensive care unit. In vitro, P. aeruginosa exploits filamentous fungi resulting in fungal killing and limitation of C. albicans growth in the host. Biofilm also play an important role as a persistent source of infectious material for recurrent episodes of VAP. Indeed, Candida spp and P. aeruginosa are the most common pathogens retrieved from endotracheal tube biofilm and tracheal secretions in patients with VAP. Finally, it has been demonstrated that previous tracheo-bronchial C. albicans colonization enhanced the incidence of P. aeruginosa pneumonia in a murine model. A recent study performed in patients requiring intubation and mechanical ventilation identified Candida spp tracheo-bronchial colonization as a risk factor for P. aeruginosa VAP. In addition, a retrospective study suggested that antifungal treatment might reduce P. aeruginosa VAP or tracheo-bronchial colonization in intubated patients with Candida spp tracheo-bronchial colonization. These interactions have major environmental and medical consequences. Experimental studies providing a better understanding of the mechanisms of interaction and clinical studies evaluating the necessity of a antifungal treatment might improve the management of these opportunistic infections.

Resume La survenue probable d’une pandemie grippale liee au virus H5N1 va entrainer un afflux massif de patients a l’hopital, notamment en reanimation. Ce texte, redige par des experts des 7 societes savantes les plus impliquees, rappelle les principes generaux de l’organisation des hopitaux en situation pandemique. Les points particuliers concernant la reanimation concernent le risque majeur de debordement et la necessite imposee pas les autorites de tutelle d’un doublement de la capacite d’accueil. La reanimation pediatrique semble particulierement exposee, les jeunes enfants, particulierement les petits nourrissons, devant etre les plus affectes par les formes graves de grippe aviaire, dans le contexte actuel de penurie relative de lits de reanimation pediatrique. Il est donc propose que les enfants de plus de 20 kg soient admis en reanimation adulte. Il est souhaitable que les unites de reanimation neonatales restent a basse densite virale. Les services de reanimation mixtes (neonatale et pediatrique) pourraient n’accueillir que les enfants. La baisse de la capacite d’admission en reanimation neonatale devrait amener a s’interroger sur une limitation des admissions de grands prematures en situation de crise. Le doublement des capacites d’admission en reanimation pediatrique pourrait se faire grâce a l’utilisation des unites de soins continus, des salles de reveil et le renforcement par du personnel, medical et non medical, libere par les deprogrammations d’activites. Ces personnels seraient encadres par les personnels habituels des unites. Des actions de formations specifiques sont a mettre en œuvre pour les personnels destines a renforcer les unites de reanimation.

La Seine, largement utilisee pour assurer l’alimentation en eau potable des Franciliens, est une ressource fragile. Et elle merite toute l’attention des producteurs d’eau qui mettent en place des partenariats pour mieux la proteger. L’une des pollutions preoccupantes au niveau des prises d’eau concerne les pesticides, dont l’origine urbaine est importante, en proche couronne de Paris.Lance en janvier 2007 a l’initiative du Syndicat des eaux d’Ile-de-France (Sedif), responsable de la production et de la distribution de l’eau potable pour 144 communes de la region parisienne, Phyt’Eaux Cites vise a limiter l’emploi de produits phytosanitaires de 73 communes et d’autres usagers urbains, dans les bassins de la Seine, l’Orge aval et l’Yvette. Ces bassins contribuent a l’alimentation de six prises d’eau potable sur la Seine en amont de Paris. Cette action, se deroule entre 2007 et 2010. Elle federe dix partenaires, publics et prives. 2007, premiere annee du programme, a permis la mise en place de l’organisation de l’action, une forte mobilisation des communes et le demarrage des actions de terrain (audits et formations). Les resultats des six premiers mois d’analyses, realisees sur quatre stations et portant sur 189 molecules phytosanitaires, ont confirme l’impact important de l’usage de phytosanitaires d’origine urbaine sur la qualite de l’eau des bassins de l’Orge aval et de l’Yvette. Des outils de communication ont ete etablis pour faciliter l’implication des communes et des habitants dans l’action.Phyt’Eaux Cites demontre la reussite d’un partenariat entre les producteurs d’eau potable pour proteger leurs ressources. Cependant, des difficultes sont encore a lever, notamment ameliorer l’implication des elus des communes dans la demarche.

Le polmoniti comunitarie rappresentano una patologia frequente. Tra i germi implicati, lo pneumococco e ancora oggi quello che predomina. La diagnosi associa una sintomatologia respiratoria con febbre e, soprattutto, una immagine alla radiografia del torace. La documentazione batteriologica e un elemento fondamentale e riposa nella maggior parte dei casi sull’esame citobatteriologico dell’espettorato. La gestione deve essere precoce e si basa sull’uso degli antibiotici. Tra le molecole utilizzate, la scelta si fa essenzialmente sul contesto clinico, la gravita del quadro e l’esistenza o meno di una terapia antibiotica precedente. A eccezione di un ricovero in rianimazione, e generalmente sufficiente una monoterapia. Schematicamente, si utilizzano come prima scelta due grandi famiglie: nella maggior parte dei casi le s-lattamine (amoxicillina), quando la clinica si orienta verso lo pneumococco, o i macrolidi nel caso si sospetti un germe intracellulare. Le nuove molecole restano attualmente delle alternative alla s-lattamina.

International audience; Background: The sequence of the beta-subunit of human chorionic gonadotropin (hCG beta varies depending on whether hCG beta is encoded by type I or type II genes. Type II genes are upregulated in trophoblast and cancer but hCG beta can be detected in the serum of nonpregnant women and healthy individuals. We aimed to determine whether monoclonal antibody (mAb) FBT11-II specifically detects hCG beta encoded by type II genes (type II hCG beta). Methods: Competitive inhibition assays with synthetic peptides, immunocytochemical and immunohistochemical studies, type II hCG beta dosing immunoassays and sequencing of CGB genes were performed. Results: Competitive inhibition assays determined that mAb FBT11-II recognizes the type II hCG beta derived peptide. CGB mRNA sequencing of JEG-3 (trophoblastic) and 124 (bladder) cell lines confirmed that JEG-3 expresses type II genes while T24 expresses exclusively type I. FBT11-II only recognizes JEG-expressed hCG beta. Placenta immunohistochemical studies confirmed that type II hCG beta expression is restricted to the syncytiotrophoblast. Immunoassays detected type II hCG beta in serum of patients with either nontrophoblastic cancers or fetal Down syndrome. Conclusion: Type II gene expression can be detected using FBT11-II. This specific recognition could improve the clinical usefulness of assays aimed at either managing aggressive tumors or screening for Down syndrome.

Pseudomonas aeruginosa is an opportunistic bacteria causing a wide variety of infections. The bacterial virulence depends on a large panel of cell-associated and extracellular factors. Quorum sensing (QS) allows cell-to-cell communication: sensing the environment, this system coordinates the expression of various genes within the bacterial population. QS is based on an interaction between a small diffusible molecule, an acylhomoserine lactone (AHL), and a transcriptionnal activator. Two QS systems, the las and rhl systems, have been identified in P. aeruginosa. The las system associates the transcriptionnal activator protein LasR and LasI responsible for the synthesis of a specific AHL: C12-HSL. This system was shown to activate the expression of a large number of virulence factors. Similarly, the rhl system associates the transcriptionnal activator protein RhlR with RhlI, which is responsible for the synthesis of another AHL: C4-HSL. Synthesis and secretion of a number of virulence factors are controlled by QS. Utilization of different animals models showed the crucial role of QS in the pathogenesis of P. aeruginosa infections. The discovery of QS has given a new opportunity to treat bacterial infection by another means than growth inhibition. New drugs inhibiting QS were recently discovered: furanone compounds can repress a large number of QS-regulated genes, including numerous P. aeruginosa virulence factor genes. Furanone administration to mice infected with P. aeruginosa significantly reduced lung bacterial load compared with the control group.

Highlights • Lower respiratory tract excretion of MERS-CoV can be observed for more than one month. • Viral excretion in multiple organs is possible, including viraemia. • Prolonged infection prevention and control measures are necessary. • Prolonged monitoring of respiratory excretion seems necessary., Background Middle East respiratory syndrome coronavirus (MERS-CoV) is an emerging coronavirus involved in severe acute respiratory distress syndrome (ARDS) and rapid renal failure. Hospital outbreak and nosocomial transmission were reported, however, several issues remain on the viral excretion course. Objectives Describe the kinetics and pattern of viral excretion in two infected patients. Study design After the initial diagnosis, blood, urine, rectal and respiratory samples were collected regularly, aliquoted and stored at −80 °C. Real-time reverse transcriptase polymerase chain reaction assay targeted the UpE and Orf1a regions of the MERS-CoV genome. Results In patient 1, who died of refractory ARDS and renal failure, MERS-CoV RNA was detected in pharyngeal and tracheal swabs, as well blood samples and urine samples until the 30th day. Rectal swabs were negative. Patient 2 also developed multiple-organ failure, but survived, with persisting renal insufficiency (creatinine clearance at 30 mL/min) and persistent interstitial syndrome albeit weaned off mechanical ventilation and no longer requiring oxygen. Tracheal aspirations were positive until the 33rd day, while nasopharyngeal swabs were negative. All other biological samples were negative. Discussion Lower respiratory tract excretion of MERS-CoV could be observed for more than one month. The most severely ill patient presented an expression of the virus in blood and urine, consistent with a type-1 interferon mediated immunological response impaired in patient 1, but developed by patient 2. These results suggest that infection control precautions must be adequately evaluated in clinical wards and laboratories exposed to MERS-CoV.

Pneumonia with septicemia caused by Pasteurella multocida was diagnosed in an immunocompetent patient exposed to a dog. This case is remarkable by two aspects: first the absence of visible cutaneous lesion, and second the localization and severity of the infection caused by P. multocida even though the patient was immunocompetent. P. multocida can cause respiratory and systemic infection, and it is a possible diagnosis in case of exposure to animals, even without history of bite or scratch. Furthermore, severe infections caused by this pathogen can occur in immunocompetent patients, so that the implication of specific host factors in the severity of the disease can be suspected. Genetic features could be one of these.

An epidemic of Ebola haemorrhagic fever (EHF) began in Guinea during December 2013, and the World Health Organization was officially notified on 23 March 2014. Since then, as of 3 December 2014, a total of 17 145 suspected, probable and confirmed EHF cases and 6070 deaths have been reported. Exposure of healthcare workers (HCWs) has resulted in more than 592 of them becoming infected, and at least 340 have died since the start of the outbreak (http://www.who.int/csr/disease/ebola/situation-reports/en/). As of this writing, three hospital-acquired infections have been documented in HCW in Western countries, one in Spain and two in the United States, both in Texas. In France, two humanitarians were infected with EHF and cared for. Preparedness to treat imported EHF relies on 12 referral centres, nine within French national territory and three in overseas territories. Preparation started after 2001; referral centres were already in use for other crises, including severe acute respiratory syndrome, H1N1 pandemic flu and Middle East respiratory syndrome coronavirus. Training and preparedness at these centres have been evaluated among European centres in several studies [1], [2] (http://epp.eurostat.ec.europa.eu/portal/page/portal/population/data/main_tables). However, EHF poses new problems, as it is the first time that such a highly contagious, untreatable and fatal epidemic disease (class 4 agent) has been imported into Europe. Several previous studies have dealt with the preparation undertaken by referral units and the possibilities of outbreaks of EHF in northern countries [3], [4], [5], but only a few studies address HCWs [3]. We thus evaluated the current feelings of HCWs in France towards their state of preparedness to treat patients with EHF. In order to be fast and up to date, we focussed on only five of the nine referral centres in France (two in Paris and one each in Lille, Lyon and Marseille). One of us (CT) went to meet the HCWs and ask them to fill a short multiple-choice questionnaire, followed by open discussion. After receipt of participant agreement, CT recorded each interview and transcribed them. CT met 83 HCWs (17 auxiliary nurses, 46 nurses and 20 physicians), 47 from infectious disease units (IDUs) and 36 from intensive care units. Overall, only 48 HCWs (58%) thought that they had received the necessary training to work with patients infected with EHF (74% among the IDU personnel), 53 (64%) felt ready to receive an infected patient in their unit (81% among the IDU personnel) and 60 (73%) wished to be personally involved in their care (83% among the IDU personnel) (Table 1). These results reveal these HCWs’ habits of working under restrictive protocols at a high risk of infection in a sanitary-crisis context in IDUs. Moreover, practice in these units is often the HCW’s personal choice; these HCWs consider it an opportunity to care for patients with rare diseases. However, it is necessary to moderate these results. Firstly, the answers to open questions reflected the gap between feeling prepared and the wish to care for a contagious patient—the latter mainly due to a sense of duty and medical ethics [6], [7] (for example, the duty to provide care despite the risks)—as well as the intellectual and professional stimulation caused by an extraordinary situation with an uncommon disease of which the medical profession has little knowledge. Secondly, the continual evolution of protocols and measures fuels the feeling of unpreparedness, although this continual evolution also justifies the opinion shared by many HCWs that protocols and measures improve each day and that they are on the right track. Table 1 Responses to questionnaire administered to HCWs at French Ebola referral healthcare centres There were significant differences in feeling prepared among auxiliary nurses (82%), physicians (80%) and nurses (50%). It is important to note that auxiliary nurses are not involved in intensive care. Physicians are more involved in the protocols process and may consequently be more confident. Nurses are the personnel who provide direct care, while auxiliary nurses are second-line personnel. Our results thus indicate that the most involved and exposed HCWs are also those who feel the least prepared and who report having the least faith in the protocols process. These outcomes may explain why 47 HCWs (58%) said that they felt unsafe concerning the potential transmission of EHF from patient to HCW. Eighty percent of these HCWs were in intensive care units and 42.6% in IDUs. Regarding occupational status, auxiliary nurses were the least likely to feel unsafe (35%), while the rates for nurses (67%) and physicians (60%) were approximately the same. HCW habits according to occupational status probably also play an important role in risk perception, but a more detailed study would be necessary to confirm this hypothesis. We have to take into consideration the fact that all interviewed auxiliary nurses worked in IDUs, where HCWs are used to working under constraining protocols and practicing in situations that place them at high risk of infection, which probably inures them to feelings of risk. Concerning HCW occupational surveillance during the provision of care for a patient with confirmed EHF, 56% of HCWs thought that surveillance was adequate. Medical and psychological monitoring was thought to be adequate in 60% and 35%, respectively, but 22% and 29% of the HCWs hesitated to answer. If we note a low confidence level regarding HCW occupational surveillance, the high rate of “don’t know” responses clearly reveals the feeling of an important lack of information on this subject. To conclude, French HCWs, especially auxiliary nurses and nurses, express concerns and doubts regarding EHF-related protocols and measures, but they retain their desire to provide care. We observed differences between units; we also found that the perception of risk is partly dependent on HCWs’ being used to working under constraining protocols and practicing in situations that place them at high risk of infection. Occupation also plays a major role in HCWs’ feelings about the Ebola crisis and the measures adopted. Occupational hierarchy, involvement and exposure influence HCWs’ speech and practices.

Resume Un echantillon de 489 medecins (263 generalistes et 215 dermatologues) a ete interroge sur les modalites de prise en charge du zona en pratique de ville. Le nombre moyen de cas de zona par medecin est de 5,6/an (98 % des medecins). Le motif principal de consultation est la douleur (80 %). Les patients beneficient d'une seule consultation (53 % des cas), de plusieurs consultations le premier mois (44 % des cas), et de plusieurs consultations pour douleurs postzosteriennes (DPZ) au-dela du premier mois (11 % des cas). Soixante pour cent des medecins ont declare prescrire un antiviral en cas de zona, surtout les medecins âges de 45 ans ou plus. Pour 60 % des medecins, le cout du traitement ne constitue pas un frein, surtout pour les medecins âges de plus de 45 ans. A la phase aigue, 93 % des medecins prescrivent antalgiques (87 %), antiseptiques (32 %), AINS (8 %), psychotropes (7 %). Les medecins attendent de l'antiviral une reduction de la frequence et de l'intensite des douleurs aigues et des DPZ. Efficacite clinique (66 %), bonne tolerance (61 %), specificite pour la cellule infectee (73 %) et absence d'effet indesirable biologique (60 %) constituent les elements determinants pour le choix d'un antiviral. La douleur associee au zona, element moteur du diagnostic et des prescriptions (traitement et prevention des douleurs aigues et des DPZ), occupe une place centrale dans la prise en charge de cette pathologie.

Flateau, C. et al.-- 16 pages, 2 figures, 26 references., We report the first case of cerebral abscess due to a novel species of Nocardia in a heart transplanted patient, and describe antimicrobial susceptibility of this isolate. As our patient was intolerant to trimethoprim-sulfamethoxazole, we also discuss alternative therapeutic options in brain abscess due to Nocardia sp.

Organisation Travail realise sous la direction de B. Guery. Introduction Candida albicans ( C. albicans ) est un champignon commensal de l’etre humain potentiellement pathogene. A l’heure actuelle, il n’existe aucun examen diagnostique fiable permettant de distinguer la colonisation de l’infection fongique invasive. Le but de ce travail est d’etudier l’implication de la reponse immunitaire dans la distinction entre colonisation et infection fongique invasive et de proposer un potentiel biomarqueur diagnostique d’infection fongique invasive. Materiels et methodes Des souris C57BL/6J âgees de 6 a 8 semaines sont instillees par voie intra-nasale avec du C. albicans (souche SC5314) a la dose de 1,5 × 10 5 UFC/souris et 3 × 10 6 UFC/souris respectivement pour le groupe colonisation pulmonaire et infection fongique invasive pulmonaire. La lesion pulmonaire, le recrutement cellulaire et le taux de cytokines dans le surnageant du lavage broncho-alveolaire sont etudies a 12, 24 et 36 heures de l’instillation. Resultats La colonisation pulmonaire a C. albicans n’induit pas de lesion pulmonaire, ni de recrutement cellulaire a 12, 24 et 36 heures et induit une secretion d’IL-22. L’infection fongique invasive pulmonaire a C. albicans induit une lesion pulmonaire, un recrutement cellulaire a type de polynucleaires neutrophiles a 12, 24 et 36 heures et induit une secretion importante d’IL-6. Un taux d’IL-6 eleve distingue l’infection fongique invasive de la colonisation pulmonaire a C. albicans avec une sensibilite et une specificite de 100 % dans notre modele. Conclusion La colonisation et l’infection fongique invasive pulmonaire a C. albicans n’induisent pas le meme type de reponse immunitaire chez l’hote. Un taux eleve d’IL-6 au niveau pulmonaire permet de distinguer l’infection fongique invasive de la colonisation pulmonaire a C. albicans .

Infection prophylaxis in high-risk patients has been evaluated in a variety of diseases. Both bacteria and fungi may be targeted. Among the most extensively studied populations are patients with hematological malignancies and those admitted to the intensive care unit. The effectiveness and ecological impact of infection prophylaxis remain actively debated.

Des etudes cliniques ont demontre pour les patients atteints d'infections compliquees de la peau et des tissus mous fortement suspectees a Staphylococcus aureus resistant a la methiciline (SARM) et traites par le linezolide (versus la vancomycine), des taux de guerison similaires et des durees de sejour plus courtes. Objectif. - Determiner le ratio cout-efficacite du linezolide versus la vancomycine selon la perspective du systeme de sante francais. Methodes. - Un modele de decision analytique a ete applique a un patient-type, de l'initiation du traitement empirique jusqu'a guerison, mort ou echec du traitement de deuxieme ligne. Les probabilites cliniques provenaient des essais cliniques. Les donnees d'utilisation de ressources (incluant la duree de traitement et la duree de sejour) et les taux de prevalence SARM etaient fournis par un panel d'expert. Les couts etaient apprecies a partir de publications. Resultats. ― Le taux de guerison en premiere ligne etait de 90,7 % pour le linezolide versus 85,5 % pour la vancomycine (apres deux lignes de traitement 98,5 % et 98 %, respectivement). Le cout total moyen etait de 7778 ?pour le linezolide versus 8777 ?pour la vancomycine pour une duree de sejour moyenne de 10,7 jours et 13,3 jours, respectivement. La prescription de linezolide etait la strategie dominante. La conclusion ne changeait pas apres realisation des analyses de sensibilite. Conclusion. ― Le linezolide peut etre considere comme une strategie cout-efficace en France dans le traitement des infections compliquees de la peau et des tissus mous suspectees a SARM.

Résumé La survenue probable d’une pandémie grippale liée au virus H5N1 va entraîner un afflux massif de patients à l’hôpital, notamment en réanimation. Ce texte, rédigé par des experts des 7 sociétés savantes les plus impliquées, rappelle les principes généraux de l’organisation des hôpitaux en situation pandémique. Les points particuliers concernant la réanimation concernent le risque majeur de débordement et la nécessité imposée pas les autorités de tutelle d’un doublement de la capacité d’accueil. La réanimation pédiatrique semble particulièrement exposée, les jeunes enfants, particulièrement les petits nourrissons, devant être les plus affectés par les formes graves de grippe aviaire, dans le contexte actuel de pénurie relative de lits de réanimation pédiatrique. Il est donc proposé que les enfants de plus de 20 kg soient admis en réanimation adulte. Il est souhaitable que les unités de réanimation néonatales restent à basse densité virale. Les services de réanimation mixtes (néonatale et pédiatrique) pourraient n’accueillir que les enfants. La baisse de la capacité d’admission en réanimation néonatale devrait amener à s’interroger sur une limitation des admissions de grands prématurés en situation de crise. Le doublement des capacités d’admission en réanimation pédiatrique pourrait se faire grâce à l’utilisation des unités de soins continus, des salles de réveil et le renforcement par du personnel, médical et non médical, libéré par les déprogrammations d’activités. Ces personnels seraient encadrés par les personnels habituels des unités. Des actions de formations spécifiques sont à mettre en œuvre pour les personnels destinés à renforcer les unités de réanimation.

Chronic allergic asthma is associated with marked inflammatory reaction, microvascular leakage and epithelium injury. As previously shown in a rat model of chronic asthma, these alterations increase lung permeability and distal airway fluid clearance. Keratinocyte growth factor (KGF) has been shown to induce epithelial cell proliferation and to protect from acute lung injuries. Therefore, the current authors evaluated the potential role of KGF treatment on lung permeability and airway inflammation in rats with chronic asthma. KGF (1 mg x kg(-1)) was administered intravenously before the last ovalbumin (OVA) challenge in sensitised rats. Permeability was assessed by the leak of radiolabelled albumin from the alveolar and systemic compartments. Histopathological analysis was also performed. Treatment with KGF decreased the leak of both markers and decreased the level of extravascular lung water in sensitised rats challenged with OVA. KGF treatment also reduced the inflammatory cell number in bronchoalveolar lavage fluid but not in bronchial mucosa. KGF markedly limited the allergen-induced alterations in epithelium integrity and the expression of the intercellular junction proteins beta-catenin and zonula occludens protein-1. In conclusion, keratinocyte growth factor administration markedly limits lung permeability and airway inflammation, an effect associated with a decrease in epithelium alterations during chronic allergic asthma. These data open new prospects in the therapeutic strategy of asthma.

The type III secretion system (TTSS) is a specialized cytotoxin-translocating apparatus of gram-negative bacteria which is involved in lung injury, septic shock, and a poor patient outcome. Recent studies have attributed these effects mainly to the ExoU effector protein. However, few studies have focused on the ExoU-independent pathogenicity of the TTSS. For the present study, we compared the pathogenicities of two strains ofPseudomonas aeruginosain a murine model of acute lung injury. We compared the CHA strain, which has a functional TTSS producing ExoS and ExoT but not ExoU, to an isogenic mutant with an inactivatedexsAgene, CHA-D1, which does not express the TTSS at all. Rats challenged with CHA had significantly increased lung injury, as assessed by the wet/dry weight ratio for the lungs and the protein level in bronchoalveolar lavage fluid (BALF) at 12 h, compared to those challenged with CHA-D1. Consistent with these findings, the CHA strain was associated with increased in vitro cytotoxicity on A549 cells, as assessed by the release of lactate dehydrogenase. CHA was also associated at 12 h with a major decrease in polymorphonuclear neutrophils in BALF, with a proinflammatory response, as assessed by the amounts of tumor necrosis factor alpha and interleukin-1β, and with decreased bacterial clearance from the lungs, ultimately leading to an increased mortality rate. These results demonstrate that the TTSS has a major role inP. aeruginosapathogenicity independent of the role of ExoU. This report underscores the crucial roles of ExoS and ExoT or other TTSS-related virulence factors in addition to ExoU.

Surgical antimicrobial prophylaxis is used to decrease postoperative wound infection. We assessed the compliance to surgical antimicrobial prophylaxis guidelines in our hospital and the impact of an information program.Observational study of clean or clean contamined surgery, during two 3-week periods, separated by a targeted information period. The following data were collected prospectively: prophylaxis indication, antimicrobial agent, timing, dose, route and duration of prophylaxis. Chi square test was used for analysis or Fischer test when available.Four hundred seventy-seven patients were enrolled - 270 and 207 for each period respectively. For both periods only 49% of prophylaxis was appropriated. When prophylaxis should be administered - 15 and 13% of patients for each period - it was antibioprophylaxy was strictly adequate with recommandations. The most common error was administration timing. Only the choice of antimicrobial agent was optimized after information period.These results are consistent with previous studies. Information program alone have no effect on the good use of antimicrobial for surgical prophylaxis. Only a policy associating organization, restriction and education could improve practices.

In their initial work published in 1972, Kerr and Currie described a new type of cell death characterized by morphological changes distinct from the features observed in necrosis [1]. The term apoptosis, from the Greek word meaning ‘falling off’, was adopted to describe this highly conserved genetic program leading to regulated cellular self-destruction. Subsequent investigations showed that this programmed cell death was crucial during fetal development and critical for controlling harmful mechanisms triggered by environmental stresses. Recent literature has defined new roles for apoptosis in the normal and injured lung. Apoptosis plays an important role not only during postnatal lung development [2] but also in the remodeling of the lung after acute lung injury (ALI) for both the elimination of excess alveolar epithelial and mesenchymal cells from resolving lesions [3, 4].

Introduction – objectifs La prise en charge des infections a enterobacteries productrices de BLSE (EBLSE) repose frequemment sur les penemes et represente ainsi un enjeu en raison des risques d’impasse therapeutique et d’emergence de carbapenemases. En France les regions Nord-pas-de-Calais et Ile de France sont les plus touchees. La cefoxitine est une cephalosporine de 2e generation caracterisee par un large spectre sur les bacilles Gram negatif et dotee in vitro d’une remarquable stabilite vis-a-vis des BLSE. Les objectifs ce travail etaient d’evaluer l’efficacite et la tolerance de la cefoxitine dans les infections urinaires a EBLSE. Materiels et methodes Il s’agit d’une etude observationnelle prospective multicentrique concernant les patients ayant presente une infection urinaire a EBLSE traitees par cefoxitine. Resultats Au total, 10 patients ont ete inclus entre juin 2012 et janvier 2014. Cinq patients presentaient une prostatite aigue, 3 une pyelonephrite compliquee tandis que 2 patients presentaient une cystite compliquee. Tous les patients ont recu la cefoxitine apres documentation microbiologique, 3 d’entre eux avaient recu initialement des carbapenemes. Aucun des patients ne presentait de bacteriemie ni de sepsis severe, toutes les souches (E. coli pour 5 patients, K. pneumoniae pour 5 patients) etaient sensibles avec une CMI ≤8 mg/L. La totalite des patients ont evolue favorablement, avec une bonne tolerance (survenue d’une eruption cutanee sans signes de gravite pour 1 patient). Conclusion La cefoxitine semble donc etre une alternative aux carbapenemes dans les infections urinaires documentees a EBLSE sans criteres de gravite.

Endogenous production of nitric oxide (NO) plays an important role in regulating vascular tone, platelet adhesion and aggregation, white cell adhesion to endothelial cells, and host defense against infection. Inhaled NO gas has been shown to be effective as a selective pulmonary vasodilator in animal models of pulmonary hypertension and in adult and infant patients with pulmonary hypertension. Inhaled NO decreases pulmonary arterial pressure and pulmonary vascular resistance and improves oxygenation. This principle has been used sucessfully to treat acute respiratory distress syndrome (ARDS), persistent pulmonary hypertension of the newborn, and pulmonary hypertension in patients undergoing cardiac surgery. These applications take advantage of the physiological effect of NO endogenously synthesized by the vascular endothelium from the amino acid L-arginine in response to stimuli such as the activation of muscarinic receptors by acetylcholine. NO diffuses from endothelium to vascular smooth muscle, where it acts as a signal-transducing factor which activates soluble guanylate cyclase in smooth muscle cells, leading to vascular relaxation.