[Ebola and others, those viruses coming from far away]. / Ebola et autres, ces virus venus d'ailleurs.

In the last decade, we faced a large number of emerging pathogens. As a consequence we had to adapt our medical practice as well as our health system. This review summarizes the main features of the recent emerging pathogens with a particular focus on the recent and ongoing Ebola outbreak, we tried to evaluate the consequences on our national health management.

First case of cerebral abscess due to a novel Nocardia species in an immunocompromised patient.

We report the first case of cerebral abscess due to a novel species of Nocardia in a heart transplant patient and describe the 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.

First cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infections in France, investigations and implications for the prevention of human-to-human transmission, France, May 2013.

In May 2013, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection was diagnosed in an adult male in France with severe respiratory illness, who had travelled to the United Arab Emirates before symptom onset. Contact tracing identified a secondary case in a patient hospitalised in the same hospital room. No other cases of MERS-CoV infection were identified among the index case's 123 contacts, nor among 39 contacts of the secondary case, during the 10-day follow-up period.

Factors associated with recurrence of catheter-related bloodstream infections in home parenteral nutrition patients.

Blood cultures from outpatients receiving home parenteral nutrition (HPN) via long-term central venous access (CVA) were retrospectively analyzed from January 2003 to May 2009. When infection of the CVA was not due to Staphylococcus aureus, Pseudomonas aeruginosa, or Candida, catheter salvage was attempted for a maximum of three consecutive infections on the same CVA. Factors influencing the time-to-next-infection were studied, whether the catheter was changed after the last infection or not. Neither the McCabe score, age, history of cancer, diabetes mellitus nor immunosuppression, curative antibiotic lock, type of bacteria, type or duration of treatment had an influence on the time-to-next-infection. The time-to-next-infection was significantly associated with the status of CVA (saved or changed) and its type (tunneled catheter with or without a cuff, or implanted port catheter).

Clostridioides difficile infection (CDI) epidemiology and patient characteristics in Switzerland.

OBJECTIVES: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

FITC-albumin as a marker for assessment of endothelial permeability in mice: comparison with 125I-albumin.

Transvascular transport of labeled-albumin is used to study endothelial permeability in experimental murine models of pulmonary infections. But radio-tagged albumin necessitates heavy safety procedures in terms of storage, manipulation and evacuation. The authors tested fluorescein isothiocyanate-tagged albumin (FITC-albumin) as a new marker for determination of endothelial permeability in a murine model of lung infection by Pseudomonas aeruginosa PAO1, in comparison with a standard method with (125)I-albumin. The mean permeability +/- SEM measured with (125)I-albumin was 2.45%/2 h +/- 0.37 for the control mice and 6.65%/2 h +/- 0.77 for the infected ones (P < .0001). With FITC-albumin, results obtained for both groups were respectively 4.96%/2 h +/- 0.64 and 11.5%/2 h +/- 1.2 (P < .0001). Spearman's rank coefficient was equal to .88 (P < .0001), showing a very strong correlation between both methods of measurement. The Bland-Altman analysis of bias revealed that there was no significant bias between FITC-albumin-derived and (125)I-albumin-derived values. The correction of the values obtained in plasma and lung homogenate supernatants by the subtraction of natural spontaneous fluorescence measured in these samples was crucial for the calculation of endothelial permeability in this new method. We believe that FITC-albumin can be useful for assessment of endothelial permeability in murine models of pulmonary diseases.

Cost-effectiveness of linezolid versus vancomycin for hospitalized patients with complicated skin and soft-tissue infections in France.

UNLABELLED: Studies have shown similar clinical cure rates and shorter length of hospitalization when using linezolid compared to vancomycin in patients with complicated skin and soft-tissue infections due to suspected or proven methicillin-resistant Staphylococcus aureus (MRSA). OBJECTIVE: This study had for aim to compare the cost-effectiveness of linezolid versus vancomycin in French healthcare settings. METHOD: A decision-analytic model followed an average patient from the initiation of an empiric treatment until cure, death or second-line treatment failure. A clinical data probability was obtained from clinical trials, resource utilization data (including treatment duration and length of hospitalization) and prevalence of MRSA was obtained from a Delphi panel, and costs from published sources. RESULTS: First-line cure rate for linezolid-treated patients was 90.7% versus 85.5% for vancomycin; the total cure rates after two lines of treatment were 98.5% and 98.0%, respectively. The average total cost was 7,778euro for linezolid versus 8,777euro for vancomycin. The mean estimated length of hospitalization after two lines of treatment was 10.7 days for linezolid versus 13.3 days for vancomycin. The increased effectiveness and reduced cost lead to more frequent prescription. This did not change after one-way sensitivity analyses. CONCLUSION: Linezolid may be considered as a cost-effective treatment for patients with complicated skin and soft-tissue infections suspected to be MRSA related in France.

Quorum-sensing activity and related virulence factor expression in clinically pathogenic isolates of Pseudomonas aeruginosa.

Respiratory isolates of Pseudomonas aeruginosa were collected from 58 critically-ill patients with ventilator-associated pneumonia. Expression of elastase and pyocyanin was assessed semi-quantitatively, while quorum-sensing activity was assessed by quantifying the levels of the autoinducers N-3-oxododecanoyl-L-homoserine lactone (C12-HSL) and N-butanoyl-L-homoserine lactone (C4-HSL). Correlations were sought between quorum-sensing activity and the expression of these two virulence factors, and all results were compared to those obtained with the laboratory reference strains PA103, a strain defective in quorum-sensing, and PAO1, a functional quorum-sensing strain. More than two-thirds of clinically pathogenic isolates had increased levels of elastase and/or pyocyanin, and high quorum-sensing activity, as assessed by autoinducer levels. However, a strong correlation between quorum-sensing activity and virulence factor production was revealed only for elastase and not for pyocyanin (C12-HSL/elastase, r = 0.7, p 2 x 10(-9); C4-HSL/elastase, r = 0.7, p 2 x 10(-9)). These data suggest that the pathogenicity of P. aeruginosa isolates from critically-ill patients with ventilator-associated pneumonia is caused, at least in part, by an increase in elastase production regulated by quorum-sensing, while increased pyocyanin production in these isolates may be regulated predominantly by mechanisms other than quorum-sensing.

[Organization of intensive care in situation of avian flu pandemic]. / Organisation de la réanimation en situation de pandémie de grippe aviaire.

The influenza pandemic will create a major increase in demand for hospital admissions, particularly for critical care services. The recommendations detailed herein have been elaborated by experts from medical societies potentially involved in this situation and focus on general hospital organization. Intensive care units will initially face high demand for admission; the Healthcare Authorities must therefore study how ICU capacity can be expanded. Pediatric intensive care units will be particularly affected by this situation of relative bed shortage, since young children, particularly infants, are expected to be affected by severe clinical forms of avian flu. Therefore, the weight threshold for admission to the adult ICU was lowered to 20 kg. Neonatal intensive care units (NICU) should remain, if possible, low viral density areas. Mixed (neonatal and pediatric) intensive care units could be dedicated to infants and children only. NICU admission of extreme premature babies should be limited in this difficult situation. Pediatric intensive care units (PICU) admission capacity could be doubled by using intermediate care and postoperative care units. The staff could be increased by doctors and nurses involved in canceled programmed activities. Healthcare workers transferred to PICU should be given special training.

[The organisation of intensive care in a situation of pandemic avian influenza]. / Organisation de la réanimation en situation de pandémie de grippe aviaire.

The development of an epidemic of avian influenza will have a major impact on the organisation and structure of the facilities for treatment. This paper, the product of collaboration between the six learned societies concerned, analyses the impact of a possible pandemic on the various aspects of management of patients requiring intensive care. It describes the organisation of hospital pathways for flu and non-flu patients with, in particular, the necessary actions in terms of separation of care facilities, the triage of patients and the cancellation of non-urgent activities. It analyses the preconditions necessary for the efficient functioning of intensive care and the predictable limiting factors. It underlines the importance of training of medical and paramedical personnel. Finally, it tackles the specific problems of paediatric intensive care: organisation, capacity for admissions and training.

[Kinetics of Pseudomonas aeruginosa virulence gene expression during chronic lung infection in the murine model]. / Cinétique d'expression des gènes de virulence de Pseudomonas aeruginosa au cours d'une infection pulmonaire chronique dans le modèle murin.

UNLABELLED: Pseudomonas aeruginosa is a Gram-negative bacillus frequently encountered in human diseases. P. aeruginosa produces a large number of secreted and cell associated virulence factors. Their production is coordinated by various systems of gene regulation. The correlation and sequential intervention of regulation systems during a pulmonary infection have not been determined yet. OBJECTIVE: The aim of this study was to analyze the expression of three P. aeruginosa virulence genes (exoS, lasI, and algD) during the first seven days of chronic lung infection. To do so, mice were infected intratracheally with agarose beads containing P. aeruginosa. RESULTS: The results were a progressive decrease of exoS transcription and an increase of algD, and lasI transcription during infection. This dynamic evolution was consistent with the clinical observation, which demonstrated a progressive loss of type III secretion system function and an increase in the mucoid phenotype development in P. aeruginosa strains from cystic fibrosis patients. CONCLUSION: The development of a P. aeruginosa pulmonary chronic infection associates a decrease of gene expression related to a type III secretion system and an increase of alginate production.

Exploring ways to improve CDI outcomes.

Clostridium difficile is an anaerobic spore-forming Gram-positive bacillus recognized as an evolving international health problem. Metronidazole and vancomycin were - until recently - the only drugs available to treat C. difficile infection (CDI). Better knowledge of the pathophysiology and the development of new drugs completely modified the management of initial episodes and recurrences of CDI. Fidaxomicin significantly reduced recurrences compared with vancomycin. New drugs are also currently evaluated (cadazolid, surotomycin, ridinilazole, rifaximin). Gut microbiota homeostasis was clearly shown to be a key determinant in recurrences as demonstrated by the development of gut microbiota transplantation and alternative microbiota substitution. Passive immunotherapy and vaccinal approaches are also currently being evaluated. In conclusion, CDI treatment has evolved with the development of new therapeutic pathways which now need to be implemented in international guidelines.

Biphasic lung injury during Streptococcus pneumoniae infection in a murine model.

OBJECTIVES: Streptococcus pneumoniae is the leading cause of community-acquired pneumonia. We aimed to analyze the epithelial response to S. pneumoniae-induced lung injury. METHODS: Using an in vitro model with 16HBE cells and experimental in vivo murine model of acute lung injury, we analyzed the epithelial response to S. pneumoniae. Lung epithelial cell monolayers were exposed to S. pneumoniae and permeability was assessed by transepithelial resistance (TER) measurement and organization and expression of junction proteins. Functional consequences were studied with an in vivo murine model measuring alveolar permeability, distal alveolar fluid clearance (DAFC), and the alveolar inflammatory response. RESULTS: In vitro, S. pneumoniae induced a dose-dependent decrease in transepithelial resistance, which was associated with significant modifications in the organization of junction proteins assessed by immunofluorescence staining and expression after 6hours of exposure. In vivo, S. pneumoniae induced a transient increase in alveolar permeability with an adequate increase in DAFC 6hours post infection. In a second phase, a permanent increased permeability was associated with a major decrease in DAFC. CONCLUSION: Overall, the epithelial response to S. pneumoniae followed a biphasic pattern with an initial reversible increase in permeability related to the alteration of tight and adherens junctions and a second phase associated with an epithelial injury with a major increase in permeability with a decreased DAFC reflecting an injured alveolar capillary barrier.

[Pneumonia with septicemia caused by Pasteurella multocida in an immunocompetent patient]. / Pneumonie à Pasteurella multocida compliquée de choc septique chez un patient non immunodéprimé

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.

Treating Clostridium difficile infection in patients presenting with hematological malignancies: Are current guidelines applicable?

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.

Proposal for shorter antibiotic therapies.

OBJECTIVES: Reducing antibiotic consumption has now become a major public health priority. Reducing treatment duration is one of the means to achieve this objective. Guidelines on the therapeutic management of the most frequent infections recommend ranges of treatment duration in the ratio of one to two. The Recommendation Group of the French Infectious Diseases Society (SPILF) was asked to collect literature data to then recommend the shortest treatment durations possible for various infections. METHODS: Analysis of the literature focused on guidelines published in French and English, supported by a systematic search on PubMed. Articles dating from one year before the guidelines publication to August 31, 2015 were searched on the website. RESULTS: The shortest treatment durations based on the relevant clinical data were suggested for upper and lower respiratory tract infections, central venous catheter-related and uncomplicated primary bacteremia, infective endocarditis, bacterial meningitis, intra-abdominal, urinary tract, upper reproductive tract, bone and joint, skin and soft tissue infections, and febrile neutropenia. Details of analyzed articles were shown in tables. CONCLUSION: This work stresses the need for new well-conducted studies evaluating treatment durations for some common infections. Following the above-mentioned work focusing on existing literature data, the Recommendation Group of the SPILF suggests specific study proposals.

Effect of different stabilized preparations of peracetic acid on biofilm.

The effect of three stabilized peracetic acid (PAA) preparations (Bioxal M), with or without surfactants, on an Escherichia coli biofilm model was studied. The biofilm was prepared in glass tubes, and was evaluated indirectly using spectrophotometry. The ability of the products to fix or remove the biofilm was determined by their detergent activity (DA). None of the preparations tested fixed the biofilm. The effect of Bioxal M-1 on the biofilm was equivalent to the control (sterile water). Bioxal M-2 and Bioxal M-3 displayed slightly positive DAs. Non-ionic surfactant improved the DA of the products. Regardless of disinfectant activity, PAA agents display different DAs depending on their formulation. This criterion could be used to select the weakest biofilm-fixing agents. Users should therefore be concerned about the efficiency of the cleaning stage of medical devices. When choosing PAA products, non-fixing ability should be considered in addition to antimicrobial activity.

[Acute invasive pulmonary aspergillosis in chronic lung disease--a review]. / Aspergillose pulmonaire aiguë invasive et pathologies pulmonaires chroniques.

INTRODUCTION: Apart from malignancies and solid organ transplant, chronic lung disease, in particular chronic obstructive pulmonary disease (COPD), is a third important predisposing factor for acute invasive pulmonary aspergillosis. STATE OF THE ART: COPD is present in 2% of patients dying from invasive aspergillosis. This opportunistic infection occurs because of an immunodeficiency linked both to altered local immunity and to systemic factors such as long term steroid treatment and malnutrition. In patients whose sputum and/or endotracheal aspirate specimens contain hyphal forms of filamentous Aspergillus, half will have a clinically significant aspergillus infection. Diagnostic tests include serum galactomannan antigen test, serum antibody titre, thoracic CT scan and bronchoalveolar lavage (BAL). The identification of fungal hyphae in BAL fluid by microscopy and/or on culture is critical for a positive diagnosis. The mortality rate for acute invasive pulmonary aspergillosis in chronic lung diseases reaches almost 100%. Antifungal monotherapy is still recommended as a first line treatment. Combined treatment can be used in refractory aspergillosis as a salvage therapy. The question of maintaining, decreasing or interrupting steroid treatment must be considered. PERSPECTIVES: Prospective studies are needed to evaluate a standardised diagnostic strategy such as exists for patients with haematological disease. Whether this will improve prognosis remains to be seen. CONCLUSION: Acute invasive pulmonary aspergillosis complicating chronic lung disease is not rare. Improved diagnosis procedures and recent therapeutic advances may have a positive impact on patient prognosis.

[Pseudomonas aeruginosa and Surfactant-associated Proteins A and D]. / Pseudomonas aeruginosa et surfactant rôle de SP-A et SP-D.

Surfactant-associated proteins A and D (SP-A and SP-D) are two pulmonary collectins that bind to bacterial, fungal and viral pathogens and have multiples classes of receptors on pneumocyte and macrophage membrane. They are chemoattractant for phagocytes, enhance uptake and killing of bacteria by macrophages and neutrophils. These molecules also act as activation ligand on macrophages and neutrophils to enhance phagocytosis, resulting in an increased bacterial clearance. Depending on activation of cells by stimuli, SP-A and SP-D modulate production of antimicrobial free radicals by phagocytes and secretion of cytokines. In vivo, SP-A deficient mice infected with Pseudomonas aeruginosa (P. aeruginosa) have decreased bacterial clearance and exacerbated inflammatory response in the lungs. Serious alterations in macrophages and increased production of reactive oxygen species were found in non-infected SP-D deficient mice. Patients with cystic fibrosis are frequently colonized by P. aeruginosa. Decreased levels of SP-A and SP-D have been measured in bronchoalveolar lavage fluid of these patients, as well as patients with acute pneumonia but no chronic lung disease. P. aeruginosa secretes various proteases, among them, elastase and protease IV have been found to degrade SP-A and SP-D and abrogate their immune function. However, further investigations are necessary to examine whether these deficiencies facilitate P. aeruginosa infections or stand as consequences.