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Background: Patients on maintenance haemodialysis (HD) have an increased risk of severe coronavirus disease 2019 (COVID-19) and a reduced response to vaccines. Data are needed to identify immune correlates of protection in this population., Methods: Following a COVID-19 outbreak among vaccinated patients in a HD unit, clinical data and serological response to BNT162b2 vaccine were retrospectively recorded., Results: Among 53 patients present in the dialysis room, 14 were infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (COVID&#95;Pos) and 39 were not. Compared with uninfected patients, COVID&#95;Pos patients more frequently had additional causes of immunosuppression (50% versus 21%; P = .046) and were more often scheduled on the Monday-Wednesday-Friday (MWF) shift (86% versus 39%; P = .002). Moreover, COVID&#95;Pos had lower anti-spike (S) immunoglobulin G (IgG) titres than uninfected patients {median 24 BAU/mL [interquartile range (IQR) 3-1163] versus 435 [99-2555]; P = .001} and lower neutralization titres [median 108 (IQR 17-224) versus 2483 (481-43 908); P = .007]. Anti-S and neutralization antibody titres are correlated (r = 0.92, P < .001). In multivariable analysis, an MWF schedule {odds ratio [OR] 10.74 [95% confidence interval (CI) 1.9-93.5], P = .014} and anti-S IgG titres 1 month before the outbreak [<205 BAU/mL: OR 0.046 (95% CI 0.002-0.29), P = .006] were independently associated with COVID-19 infection. None of the patients with anti-S IgG >284 BAU/mL got infected. Ten of 14 COVID&#95;Pos patients were treated with casirivimab and imdevimab. No patient developed severe disease., Conclusions: Anti-S IgG titre measured prior to exposure correlates to protection from SARS-CoV-2 infection in HD patients. BNT162b2 vaccination alone or in combination with monoclonal antibodies prevented severe COVID-19., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed., Objectives: To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors., Participants: Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative)., Design: Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics., Main Measures: Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey., Key Results: The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16), and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms., Conclusions: More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society., (© 2022. The Author(s) under exclusive licence to Society of General Internal Medicine.)

Objectives: To describe the therapeutic drug monitoring (TDM) of cefepime in non-critically ill adults and compare four different ways of dosing: conventional table-based; empirically adjusted following TDM; individualized based on a population pharmacokinetic (PopPK) model without TDM; and TDM-adjusted with a Bayesian approach integrating TDM and PopPK., Methods: We conducted a retrospective study in a tertiary centre to examine the current practice of TDM and to evaluate the potential for improvement by PopPK-based software individualization. The prediction of trough concentrations and the total daily doses (TDD) prescribed according to each approach were compared by calculating the mean logarithmic bias and the root mean squared error, complemented by linear regression and variance analysis., Results: Among 168 trough concentrations in 119 patients (median: 12 mg/L), 38.6% of measurements exceeded 15 mg/L, the reported threshold for neurotoxicity. Nine patients developed neurotoxicity. The prediction performance of PopPK alone for trough concentrations was moderate, but clearly improved after integration of TDM. Accordingly, TDD were significantly lower for a priori PopPK-based dosage (mean: 2907 mg/24 h) compared with actual table-based dosage (4625 mg/24 h, P  < 0.001). They were also lower for a posteriori dosage based on PopPK and TDM (3377 mg/24 h) compared with actual dosage after empirical TDM (4233 mg/24 h, P  < 0.001), as model-based adjustment privileged more frequent administrations., Conclusions: Our observations support routine TDM of cefepime to prevent overdosing and subsequent toxicity in the non-critically ill. Software-based individualization seems promising to optimize the benefits of TDM, but has little potential to replace it., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Objectives: We aimed to evaluate the impact of the 10th version of European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints table, where most antipseudomonal drugs but meropenem are now categorised as "Susceptible, increased exposure" and labelled I, on meropenem prescription for Pseudomonas aeruginosa infections., Methods: In this retrospective single-centre observational study, we analysed antimicrobial therapies prescribed after susceptibility testing in all consecutive adult patients treated for P. aeruginosa infections between 01.08.2019 and 30.07.2020 in Lausanne University Hospital, Switzerland. We collected epidemiological, microbiological, clinical data, antimicrobial therapy, and infectious diseases specialists (IDs) consultations' data. The primary outcome was the prescription of meropenem to treat P. aeruginosa infections after release of susceptibility testing results. Secondary outcomes were: the use of increased dosage for non-meropenem anti-pseudomonal drugs, and IDs' consultations rates after susceptibility testing was made available., Results: Among the 264 patients included, 40 (15.2%) received meropenem, 3.4% (5/148) before EUCAST update versus 30.2% (35/116) after (p < 0.001). Supervision and counselling from IDs and the use of increased dosages of non-carbapenem antibiotics also increased respectively (40.5% (60/148) vs 62.9% (73/116), P < 0.001); (55.5% (76/148) vs 88.9% (72/116), P < 0.001). Factors associated with these increments could not be adequately modelled., Conclusions: The change to 2020 EUCAST criteria might be associated with increased odds of meropenem prescription for the treatment of P. aeruginosa infections stressing the need of prescribers' education and the importance of antibiotic stewardship interventions., (Copyright © 2021 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Pseudomonas aeruginosa is a pathogen frequently encountered in healthcare-associated infections and immunocompromised patients. In bacteremia, this pathogen is associated with higher mortality than other Gram-negative pathogens. This increase in mortality was also found globally for multi-resistant compared to susceptible strains. Several factors have been associated with the development of resistance: previous ICU stay, use of carbapenems, and comorbidities were identified in multivariate analysis. In the therapeutic choice, previous antibiotic treatment remains the strongest driver suggesting a potential resistant strain. These risk factors will decide whether multi-resistant strains must be considered in the empiric coverage. For susceptible strains, a single agent can be used, β-lactams are usually the first choice. Associations do not provide any advantage on mortality. Optimization of pharmacokinetic/pharmacodynamic parameters, such as prolonged infusion (for time-dependent antibiotics), increased dosage (for concentration-dependent antibiotics), and therapeutic drug monitoring, also influences the outcome. The increasing number of resistant strains led the clinician to use either recently approved new molecules but also associations. For multi-resistant strains, new molecules such as ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol have shown an adequate activity against P. aeruginosa. Older molecules like colistin and fosfomycin are also used in this indication. The complexity of the resistance and consequences on a larger scale of antibiotic prescription will probably lead to more individualized prescriptions., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Scope: In 2009, the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) published the first treatment guidance document for Clostridioides difficile infection (CDI). This document was updated in 2014. The growing literature on CDI antimicrobial treatment and novel treatment approaches, such as faecal microbiota transplantation (FMT) and toxin-binding monoclonal antibodies, prompted the ESCMID study group on C. difficile (ESGCD) to update the 2014 treatment guidance document for CDI in adults., Methods and Questions: Key questions on CDI treatment were formulated by the guideline committee and included: What is the best treatment for initial, severe, severe-complicated, refractory, recurrent and multiple recurrent CDI? What is the best treatment when no oral therapy is possible? Can prognostic factors identify patients at risk for severe and recurrent CDI and is there a place for CDI prophylaxis? Outcome measures for treatment strategy were: clinical cure, recurrence and sustained cure. For studies on surgical interventions and severe-complicated CDI the outcome was mortality. Appraisal of available literature and drafting of recommendations was performed by the guideline drafting group. The total body of evidence for the recommendations on CDI treatment consists of the literature described in the previous guidelines, supplemented with a systematic literature search on randomized clinical trials and observational studies from 2012 and onwards. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) system was used to grade the strength of our recommendations and the quality of the evidence. The guideline committee was invited to comment on the recommendations. The guideline draft was sent to external experts and a patients' representative for review. Full ESCMID endorsement was obtained after a public consultation procedure., Recommendations: Important changes compared with previous guideline include but are not limited to: metronidazole is no longer recommended for treatment of CDI when fidaxomicin or vancomycin are available, fidaxomicin is the preferred agent for treatment of initial CDI and the first recurrence of CDI when available and feasible, FMT or bezlotoxumab in addition to standard of care antibiotics (SoC) are preferred for treatment of a second or further recurrence of CDI, bezlotoxumab in addition to SoC is recommended for the first recurrence of CDI when fidaxomicin was used to manage the initial CDI episode, and bezlotoxumab is considered as an ancillary treatment to vancomycin for a CDI episode with high risk of recurrence when fidaxomicin is not available. Contrary to the previous guideline, in the current guideline emphasis is placed on risk for recurrence as a factor that determines treatment strategy for the individual patient, rather than the disease severity., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The magnitude and scope of Clostridioides difficile infection (CDI) has changed with an increase in incidence and severity. The epidemiology of CDI is not well known in France due to difficulties to conduct large continuous surveillance. The objectives were to compare the characteristics of patients with CDI collected through repeated point prevalence survey via DIFTEC™, a free electronic tool, with those from previous French or European studies., Methods: DIFTEC™ was developed to evaluate epidemiological burden, diagnostic strategies and management of CDI in France. National and European guidelines were used for definitions. A literature review of studies conducted in Western Europe on CDI and published between January 2008 and May 2018 was done to compare their data with those included in the DIFTEC™ database., Results: From January 2016, to December 2017, 455 CDI episodes from 22 French hospitals were included. Most of CDI cases were health-care associated (HCA) (78%). The comparison between included patients and French literature data showed that the rates of previous antibiotics exposure, crude mortality and recurrence were not statistically different. However HCA-CDI was significantly more frequent in the DIFTEC™ study. Gender distribution, recurrence and crude mortality rates were not statistically different compared to European data. HCA-CDI was more frequent in the DIFTEC™ study whereas previous treatment with proton pump inhibitors and antibiotics were significantly higher in European studies., Discussion: These results illustrated the added value of a new tool for increasing the reliable knowledge of CDI in France based on epidemiological surveillance implemented in health-care settings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: In the last 36 months: AH had non conflict of interest to declare; AG, AMR and AV declared non-financial support from Astellas; BG received a grant from MSD and personal fees from Astellas; DB declared personal fees from Astellas; FB received grant from Astellas, Sanofi Pasteur, Anios, MSD, Biomérieux, Quidel Buhlman and Diasorin, personal fees from Astellas, Pfizer, Sanofi Pasteur and MSD, and non-financial support from Astellas, Anios and MSD; NK declared a grant from FINOVI, personal fees from Astellas and Alere, and non-financial fees from Astellas and Anios; PV obtained a grant from MSD and received personal fees from Astellas, Sanofi Pasteur and Bioscience., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: To describe the characteristics, management and outcomes of hospitalised patients with Clostridioides difficile infection (CDI) treated with and without fidaxomicin., Methods: This prospective, multicentre, observational study (DAFNE) enrolled hospitalised patients with CDI, including 294 patients treated with fidaxomicin (outcomes recorded over a 3-month period) and 150 patients treated with other CDI therapies during three 1-month periods. The primary endpoint was baseline and CDI characteristics of fidaxomicin-treated patients., Results: At baseline, the fidaxomicin-treated population included immunocompromised patients (39.1%) and patients with severe (59.2%) and recurrent (36.4%) CDI. Fidaxomicin was associated with a high rate of clinical cure (92.2%) and low CDI recurrence (16.3% within 3 months). Clinical cure rates were ≥90% in patients aged ≥65 years, those receiving concomitant antibiotics and those with prior or severe CDI. There were 121/296 (40.9%) patients with adverse events (AEs), 5.4% with fidaxomicin-related AEs and 1.0% with serious fidaxomicin-related AEs. No fidaxomicin-related deaths were reported., Conclusions: Fidaxomicin is an effective and well-tolerated CDI treatment in a real-world setting in France, which included patients at high risk of adverse outcomes.Trial registration: Description of the use of fidaxomicin in hospitalised patients with documented Clostridium difficile infection and the management of these patients (DAFNE), NCT02214771, www.ClinicalTrials.gov.

The Swiss societies of Infectious Diseases, Pediatric Cardiology and Cardiology and the Pediatric Infectious Disease Group of Switzerland present the current update on infective endocarditis prophylaxis in a joint initiative. The major focus of the revised recommendations is a comprehensive prevention campaign for all patients at risk for infective endocarditis. Antibiotic prophylaxis is recommended only for individuals at high risk. Within this high-risk group there is a ranking order, and the conditions are presented accordingly. Antibiotic prophylaxis is no longer recommended for patients with unrepaired ventricular septal defects and patent ductus arteriosus. Recommendations for antibiotic prophylaxis for the prevention of infective endocarditis are categorized in dental and non-dental interventions.

Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.

Background: Coronavirus disease 2019 (COVID-19) can result in profound changes in blood coagulation. The aim of the study was to determine the incidence and predictors of venous thromboembolic events (VTE) among patients with COVID-19 requiring hospital admission. Subjects and Methods . We performed a retrospective study at the Lausanne University Hospital with patients admitted because of COVID-19 from February 28 to April 30, 2020., Results: Among 443 patients with COVID-19, VTE was diagnosed in 41 patients (9.3%; 27 pulmonary embolisms, 12 deep vein thrombosis, one pulmonary embolism and deep vein thrombosis, one portal vein thrombosis). VTE was diagnosed already upon admission in 14 (34.1%) patients and 27 (65.9%) during hospital stay (18 in ICU and nine in wards outside the ICU). Multivariate analysis revealed D-dimer value > 3,120 ng/ml ( P < 0.001; OR 15.8, 95% CI 4.7-52.9) and duration of 8 days or more from COVID-19 symptoms onset to presentation ( P 0.020; OR 4.8, 95% CI 1.3-18.3) to be independently associated with VTE upon admission. D-dimer value ≥ 3,000 ng/l combined with a Wells score for PE ≥ 2 was highly specific (sensitivity 57.1%, specificity 91.6%) in detecting VTE upon admission. Development of VTE during hospitalization was independently associated with D-dimer value > 5,611 ng/ml ( P < 0.001; OR 6.3, 95% CI 2.4-16.2) and mechanical ventilation ( P < 0.001; OR 5.9, 95% CI 2.3-15.1)., Conclusions: VTE seems to be a common COVID-19 complication upon admission and during hospitalization, especially in ICU. The combination of Wells ≥ 2 score and D - dimer ≥ 3,000 ng/l is a good predictor of VTE at admission., Competing Interests: All authors state that they have no conflict of interest to report., (Copyright © 2020 Eleftheria Kampouri et al.)

Background: Gut dysbiosis due to the adverse effects of antibiotics affects outcomes of lung infection. Previous murine models relied on significant depletion of both gut and lung microbiota, rendering the analysis of immune gut-lung cross-talk difficult. Here, we study the effects of antibiotic-induced gut dysbiosis without lung dysbiosis on lung immunity and the consequences on acute P. aeruginosa lung infection., Methods: C57BL6 mice received 7 days oral vancomycin-colistin, followed by normal regimen or fecal microbial transplant or Fms-related tyrosine kinase 3 ligand (Flt3-Ligand) over 2 days, and then intra-nasal P. aeruginosa strain PAO1. Gut and lung microbiota were studied by next-generation sequencing, and lung infection outcomes were studied at 24 h. Effects of vancomycin-colistin on underlying immunity and bone marrow progenitors were studied in uninfected mice by flow cytometry in the lung, spleen, and bone marrow., Results: Vancomycin-colistin administration induces widespread cellular immunosuppression in both the lung and spleen, decreases circulating hematopoietic cytokine Flt3-Ligand, and depresses dendritic cell bone marrow progenitors leading to worsening of P. aeruginosa lung infection outcomes (bacterial loads, lung injury, and survival). Reversal of these effects by fecal microbial transplant shows that these alterations are related to gut dysbiosis. Recombinant Flt3-Ligand reverses the effects of antibiotics on subsequent lung infection., Conclusions: These results show that gut dysbiosis strongly impairs monocyte/dendritic progenitors and lung immunity, worsening outcomes of P. aeruginosa lung infection. Treatment with a fecal microbial transplant or immune stimulation by Flt3-Ligand both restore lung cellular responses to and outcomes of P. aeruginosa following antibiotic-induced gut dysbiosis.

Background: We report the results of an observational study of arteriovenous fistula (AVF) cannulation and haemostasis practices in France., Methods: The study (sponsored by Brothier Pharmaceutical Inc.) was conducted in 150 dialysis units. Data obtained from 150 supervisory nurses, 1538 nurses and 3588 patients with an AVF were analysed., Results: The nurses reported using rope-ladder, area or buttonhole cannulation techniques in 68, 26 and 6% of cases, respectively. Metal needles were used most frequently (64%), with mainly a diameter of 15 G or 16 G. The needle was introduced with the bevel up in 56% of cases. Compression applied using dressings (in particular, pure calcium alginate dressings) was the method of choice for haemostasis of the puncture sites and was assessed as being strong by most of the nurses and very strong in cases of prolonged bleeding. Most (82%) of the patients reported the use of local anaesthetic before cannulation and 23% reported an allergic skin reaction to the anaesthetic. Bleeding of the puncture sites lasted for >10 min for 48% of the patients and it reappeared between two sessions for 29% of the patients. Whereas the nurses appeared to have a good understanding of AVF, more than half of the patients did not know how to care for it, with 55% requiring more information., Conclusions: This study underlines the lack of national consensus concerning AVF cannulation practices. It suggests that haemostasis methods of the puncture sites can be improved and it highlights the need to improve patient knowledge., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Purpose of Review: The purpose of the review is to provide all the recent data focusing on the diagnostic and treatment of Clostridioides difficile infection in patients admitted in the ICU., Recent Findings: In the ICU, diagnosis remains complicated with a large number of alternative diagnosis. The treatment classically relies on vancomycin but fidaxomicin and fecal microbiota transplantation are now potential solutions in selected indications., Summary: Data on ICU-related CDI remain limited and conflicting. To date, there is no unique and simple way to obtain a diagnosis for CDI, the combination of clinical signs and a two-step testing algorithm remains the recommended gold-standard. Two molecules can be proposed for first line treatment: vancomycin and fidaxomicin. Although metronidazole may still be discussed as a treatment option for mild CDI in low-risk patients, its use for ICU-patients does not seem reasonable. Several reports suggest that fecal microbiota transplantation could be discussed, as it is well tolerated and associated with a high rate of clinical cure. CDI is a dynamic and active area of research with new diagnostic techniques, molecules, and management concepts likely changing our approach to this old disease in the near future.

Background: Infectious endocarditis is a life-threatening disease, requiring prompt and accurate diagnosis. The aim of this article is to perform a systematic review and meta-analysis of the literature to estimate the performance of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) for the diagnosis of native valve endocarditis (NVE)., Methods: Selected articles evaluating the diagnostic accuracy of 18 F-FDG PET/CT in patients with suspected NVE, resulting from a comprehensive literature search through the PubMed/MEDLINE and Cochrane library databases until April 2020, were included for the systematic review and meta-analysis., Results: Seven studies (351 episodes of suspected NVE) were included. 18 F-FDG PET/CT yielded a pooled sensitivity of 36.3% and a pooled specificity of 99.1% for the diagnosis of NVE. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 8.3, 0.6, and 15.3, respectively. The sensitivity increased using contemporary PET/CT device with state-of-the-art patient preparation as well as innovative image acquisitions or adding the results of 18 F-FDG PET/CT in a multimodality strategy., Conclusions: In our systematic review and meta-analysis, 18 F-FDG PET/CT yielded a poor pooled sensitivity with an otherwise excellent pooled specificity for the diagnosis of NVE; however, several factors may increase the sensitivity without affecting the specificity and these factors should be better evaluated in future studies.

Since its emergence in December 2019, scientific knowledge about the SARS-CoV-2 virus has evolved rapidly but, due to the complexity and novelty of this infection and its political and economic stakes, much remains to be clarified. Thousands of studies have already been published and scientific research is constantly evolving. In this multitude of information, we offer an update of the knowledge currently available. A limitation of the propagation, the understanding of the functioning of the virus and its clinical manifestations, the administration of specific treatments, rapid and reliable diagnostic tools are the basis of the fight against this germ, which is still little known today., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Antibiotic resistance has become a major medical problem of our time. In 2015, the World Health Organisation (WHO) endorsed a global action plan in response. One of the main axes of this plan has been the sustained development of new antimicrobials. Despite its challenges, over half a dozen new substances have become clinically available in the last decade. Here, we review a selection of these novel antimicrobial and their applications and discuss their possible use in the clinical setting., Competing Interests: Sylvain Meylan est consultant pour Antimicrobial Memory Recovery Initiative (Global Antibiotic Research & Development Partnership (GARDP) – Drugs for Neglected Diseases Initiative (DNDi)). Benoît Guery: participation à l’advisory board d’Astellas Pharma, et Merck Sharp and Dohme (MSD). Vera Portillo n’a déclaré aucun conflit d’intérêts en relation avec cet article.

Background: Fidaxomicin is a recommended treatment for Clostridioides difficile infection (CDI) and reduces CDI recurrence incidence versus vancomycin. An extended-pulsed fidaxomicin (EPFX) regimen further reduces recurrence frequency. However, the pharmacokinetic profile of fidaxomicin in an EPFX regimen is unknown., Objectives: To evaluate plasma and stool concentrations of fidaxomicin and its metabolite, OP-1118, after EPFX administration for CDI., Methods: In the Phase 3b/4 EXTEND trial, patients aged ≥60 years with toxin-confirmed CDI were randomized to receive EPFX (oral fidaxomicin twice daily, Days 1-5; once daily on alternate days, Days 7-25). Fidaxomicin and OP-1118 concentrations were determined using post-dose plasma samples obtained on Days 5 ± 1, 12 ± 1 and 25/26, and post-dose stool samples obtained on Days 5 ± 1, 12 ± 1 and 26 ± 1., Results: Plasma samples from 14 patients were included in the pharmacokinetic analysis; 12 of these patients provided stool samples. Median (range) plasma concentrations of fidaxomicin on Day 5 ± 1 and Day 25/26 were 0.0252 (0.0038-0.1220) mg/L and 0.0069 (0-0.0887) mg/L, respectively, and those of OP-1118 were 0.0648 (0.0142-0.3250) mg/L and 0.0206 (0-0.3720) mg/L, respectively. Median (range) stool concentrations of fidaxomicin and OP-1118 on Day 26 ± 1 were 272.5 (0-524) mg/kg and 280.5 (0-1120) mg/kg, respectively., Conclusions: EPFX treatment maintained fidaxomicin stool concentrations above the C. difficile MIC90 until Day 26 ± 1. Systemic exposure to fidaxomicin and OP-1118 was low throughout and there was no evidence of accumulation in plasma or stool during treatment., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The gut and lungs are anatomically distinct, but potential anatomic communications and complex pathways involving their respective microbiota have reinforced the existence of a gut-lung axis (GLA). Compared to the better-studied gut microbiota, the lung microbiota, only considered in recent years, represents a more discreet part of the whole microbiota associated to human hosts. While the vast majority of studies focused on the bacterial component of the microbiota in healthy and pathological conditions, recent works have highlighted the contribution of fungal and viral kingdoms at both digestive and respiratory levels. Moreover, growing evidence indicates the key role of inter-kingdom crosstalks in maintaining host homeostasis and in disease evolution. In fact, the recently emerged GLA concept involves host-microbe as well as microbe-microbe interactions, based both on localized and long-reaching effects. GLA can shape immune responses and interfere with the course of respiratory diseases. In this review, we aim to analyze how the lung and gut microbiota influence each other and may impact on respiratory diseases. Due to the limited knowledge on the human virobiota, we focused on gut and lung bacteriobiota and mycobiota, with a specific attention on inter-kingdom microbial crosstalks which are able to shape local or long-reached host responses within the GLA., (Copyright © 2020 Enaud, Prevel, Ciarlo, Beaufils, Wieërs, Guery and Delhaes.)

Background: While respiratory viral infections are recognized as a frequent cause of illness in hematopoietic stem cell transplantation (HSCT) recipients, HCoV-OC43 infections have rarely been investigated as healthcare-associated infections in this population., Objectives: In this report, HCoV-OC43 isolates collected from HSCT patients were retrospectively characterized to identify potential clusters of infection that may stand for a hospital transmission., Study Design: Whole-genome and S gene sequences were obtained from nasal swabs using next-generation sequencing and phylogenetic trees were constructed. Similar identity matrix and determination of the most common ancestor were used to compare clusters of patient's sequences. Amino acids substitutions were analysed., Results: Genotypes B, E, F and G were identified. Two clusters of patients were defined from chronological data and phylogenetic trees. Analyses of amino acids substitutions of the S protein sequences identified substitutions specific for genotype F strains circulating among European people., Conclusions: HCoV-OC43 may be implicated in healthcare-associated infections., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Clostridioides ( Clostridium ) difficile infection (CDI) is diagnosed using clinical signs and symptoms plus positive laboratory tests. Recurrence of CDI after treatment is common, and coinfection with other enteric pathogens may influence clinical outcomes., Methods: We aimed to assess rates of C difficile positivity, by enzyme-linked immunosorbent assay (ELISA) toxin A/B and BioFire FilmArray, and the effect of enteric coinfection on clinical outcomes, using samples from the EXTEND study of extended-pulsed fidaxomicin (EPFX) versus standard vancomycin., Results: All 356 randomized and treated patients tested positive for C difficile toxin A/B by local tests; a majority (225 of 356, 63.2%) also tested positive by both ELISA and BioFire. Most stool samples taken at screening tested positive for C difficile only using BioFire (EPFX: 112 of 165, 69.7%; vancomycin: 118 of 162, 72.8%). Of the 5 patients who failed treatment and had stool samples available, all (1) had tested negative for C difficile by BioFire at screening and (2) were negative by ELISA at time of treatment failure. When analyzed by BioFire results at screening, rates of sustained clinical cure at 30 days after end of treatment were numerically higher with EPFX than with vancomycin for almost all patients, except for those who tested negative for C difficile but positive for another pathogen. However, these outcome differences by presence of coinfection did not reach statistical significance. Whole-genome sequencing analysis determined that 20 of 26 paired samples from patients with recurrence were reinfections with the same C difficile strain., Conclusions: Testing for presence of copathogens in clinical trials of antibiotics could help to explain clinical failures., (© The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Clostridioides difficile (formerly Clostridium ) is a major cause of healthcare associated diarrhea, and is increasingly present in the community. Historically, C difficile infection was considered easy to diagnose and treat. Over the past two decades, however, diagnostic techniques have changed in line with a greater understanding of the physiopathology of C difficile infection and the use of new therapeutic molecules. The evolution of diagnosis showed there was an important under- and misdiagnosis of C difficile infection, emphasizing the importance of algorithms recommended by European and North American infectious diseases societies to obtain a reliable diagnosis. Previously, metronidazole was considered the reference drug to treat C difficile infection, but more recently vancomycin and other newer drugs are shown to have higher cure rates. Recurrence of infection represents a key parameter in the evaluation of new drugs, and the challenge is to target the right population with the adapted therapeutic molecule. In multiple recurrences, fecal microbiota transplantation is recommended. New approaches, including antibodies, vaccines, and new molecules are already available or in the pipeline, but more data are needed to support the inclusion of these in practice guidelines. This review aims to provide a baseline for clinicians to understand and stratify their choice in the diagnosis and treatment of C difficile infection based on the most recent data available., Competing Interests: Declaration of interests We have read and understood the BMJ policy on declaration of interests and declare the following interests: BG reports personal fees, and non-financial support from Astellas, personal fees and non-financial support from MSD TG reports personal fees, and non-financial support from Astellas, personal fees and non-financial support from MSD FB reports grants, personal fees, and non-financial support from Astellas, personal fees from Pfizer, grants, personal fees and non-financial support from MSD Further details of The BMJ policy on financial interests is here: https://www.bmj.com/about-bmj/resources-authors/forms-policies-and-checklists/declaration-competing-interests, (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

For the last decades, the timing of antimicrobial therapy has remained a hotly debated topic in sepsis as well as other infectious diseases like community-acquired pneumonia (CAP) or bacterial meningitis (CABM). In CAP, a relationship between the time to antibiotic administration and mortality was found only in the largest cohort, but all these studies were retrospective and of low quality. In CABM, the level of evidence remains also limited, but there is now a good body of evidence linking the delay to antibiotic administration to unfavorable outcome. The European guidelines strongly suggest that time period should not exceed 1 hour. Finally, in sepsis, if the 1-hour cut-off remains debatable for sepsis patients, early administration (within 3 hours) is recommended in sepsis and sepsis shock as suggested by the surviving sepsis campaign recommendations. To conclude, all these data are in favor of a potential link between the time to antibiotic administration and survival, but we still miss randomized controlled studies to give a definite answer., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Poor outcomes following Clostridium difficile infection (CDI) have been associated with advanced age, presence of cancer and C. difficile PCR-ribotype 027. The impact of baseline risk factors on clinical outcomes was evaluated using data from the EXTEND study, in which rate of sustained clinical cure (SCC) in the overall population was significantly higher with an extended-pulsed fidaxomicin (EPFX) regimen than with vancomycin. Patients aged ≥ 60 years received EPFX (fidaxomicin 200 mg twice daily, days 1-5; once daily on alternate days, days 7-25) or vancomycin (125 mg four times daily, days 1-10). We analysed outcomes by advanced age, cancer diagnosis, CDI severity, prior CDI occurrence and infection with PCR-ribotype 027. The primary endpoint was SCC 30 days after end of treatment (EOT; clinical response at test-of-cure with no subsequent recurrence). SCC rates 30 days after EOT did not differ significantly between EPFX (124/177, 70.1%) and vancomycin (106/179, 59.2%) regardless of age, cancer diagnosis, CDI severity and prior CDI. In patients with PCR-ribotype 027, SCC rate 30 days after EOT was significantly higher with EPFX (20/25, 80%) than with vancomycin (9/22, 40.9%) (treatment difference, 39.1%; 95% CI, 13.2-64.9; P = 0.006). Subgroup analyses from the EXTEND study suggest that EPFX is efficacious as a potential treatment for CDI regardless of age, cancer diagnosis, infection with PCR-ribotype 027, CDI severity or prior CDI. ClinicalTrials.gov identifier: NCT02254967.

Fecal microbiota transplantation (FMT) raised, in the recent years, a growing interest, mostly in Clostridioides difficile infections (CDI). The concept of FMT is quite simple based on the administration of fecal matter from a healthy donor to a patient with a disease related to the gut microbiota imbalance (dysbiosis). Although the theory seems straightforward, the fine mechanisms are multiple and not yet completely understood. In Switzerland, FMT is considered as a drug under the pharmacist responsibility. The only official indication for FMT is multi-recurrent CDI. For practical reasons, most of the FMT are performed with fresh stools, but development of frozen forms and capsules should considerably enhance treatment delivery. Other indications are currently investigated but not yet in the clinical routine., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Purpose of Review: This review details the management of Pseudomonas aeruginosa infections covering both current and future treatment options that are and may be available for the clinicians., Recent Findings: Pseudomonas aeruginosa infections are a great concern in hospital-acquired infections with very limited therapeutic options. The increasing antibiotic resistance has led to a need for different treatment choices that range from the use of new antibiotics to new nonantibiotic alternative agents to kill or disarm the pathogen., Summary: New molecules such as ceftolozane-tazobactam, ceftazidime-avibactam, and imipenem-relebactam have shown an adequate activity against P. aeruginosa, especially against multidrug resistance strains. Other nonantibiotic alternative treatments, such as antibodies, bacteriocins or phage therapy, have shown promising results, but future clinical studies are needed.

Respiratory tract infections represent a major cause of morbidity and mortality despite the progress made in their diagnosis and treatment. Since the clinical presentation of a viral or bacterial infection is often similar, the identification of a biomarker that could guide the clinician whether or not to introduce an antibiotic therapy is crucial. C-reactive protein and procalcitonin are the most commonly used biomarkers as a diagnostic tool for respiratory tract infections. New biomarkers show promising results for assessing the severity of infection and identifying patients at risk for complications. However, the use of biomarkers has limitations and the diagnosis of a bacterial infection should not be based solely on the measurement of a biomarker., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Infections with Pseudomonas aeruginosa have become a real concern in hospital-acquired infections, especially in critically ill and immunocompromised patients. The major problem leading to high mortality lies in the appearance of drug-resistant strains. Therefore, a vast number of approaches to develop novel anti-infectives is currently pursued. Diverse strategies range from killing (new antibiotics) to disarming (antivirulence) the pathogen. In this review, selected aspects of P. aeruginosa antimicrobial resistance and infection management will be addressed. Many studies have been performed to evaluate the risk factors for resistance and the potential consequences on mortality and attributable mortality. The review also looks at the mechanisms associated with resistance - P. aeruginosa is a pathogen presenting a large genome, and it can develop a large number of factors associated with antibiotic resistance involving almost all classes of antibiotics. Clinical approaches to patients with bacteremia, ventilator-associated pneumonia, urinary tract infections and skin soft tissue infections are discussed. Antibiotic combinations are reviewed as well as an analysis of pharmacokinetic and pharmacodynamic parameters to optimize P. aeruginosa treatment. Limitations of current therapies, the potential for alternative drugs and new therapeutic options are also discussed., Competing Interests: Disclosure and potential conflicts of interest: The authors declare no conflicts of interest. The International Committee of Medical Journal Editors (ICMJE) Potential Conflicts of Interests form for the authors are available for download at http://www.drugsincontext.com/wp-content/uploads/2018/04/dic.212527-COI.pdf

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., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Clostridium difficile infection causes severe complications and frequently recurs. An extended-pulsed fidaxomicin regimen might facilitate sustained clinical cure by prolonging C difficile suppression and supporting gut microbiota recovery. We aimed to compare clinical outcomes of extended-pulsed fidaxomicin with standard vancomycin., Methods: In this randomised, controlled, open-label, superiority study, we recruited hospitalised adults aged 60 years and older with confirmed C difficile infection at 86 European hospitals. Patients were randomly assigned (1:1) using an interactive web response system to receive extended-pulsed fidaxomicin (200 mg oral tablets, twice daily on days 1-5, then once daily on alternate days on days 7-25) or vancomycin (125 mg oral capsules, four times daily on days 1-10), stratified by baseline C difficile infection severity, cancer presence, age (≥75 years vs <75 years), and number of previous C difficile infection occurrences. The primary endpoint was sustained clinical cure 30 days after end of treatment (day 55 for extended-pulsed fidaxomicin and day 40 for vancomycin), assessed in all randomised patients who met the inclusion criteria and received at least one dose of study medication (modified full analysis set). Adverse events were assessed in all patients who received at least one dose of study drug. The study is registered with ClinicalTrials.gov, number NCT02254967., Findings: Between Nov 6, 2014, and May 5, 2016, 364 patients were enrolled and randomly assigned to receive extended-pulsed fidaxomicin or vancomycin. 362 patients received at least one dose of study medication (181 in each group). 124 (70%) of 177 patients in the modified full analysis set receiving extended-pulsed fidaxomicin achieved sustained clinical cure 30 days after end of treatment, compared with 106 (59%) of 179 patients receiving vancomycin (difference 11% [95% CI 1·0-20·7], p=0·030; odds ratio 1·62 [95% CI 1·04-2·54]). Incidence of treatment-emergent adverse events did not differ between extended-pulsed fidaxomicin (121 [67%] of 181) and vancomycin (128 [71%] of 181) treatment arms. One death in the vancomycin arm was considered by the investigator to be related to study drug., Interpretation: Extended-pulsed fidaxomicin was superior to standard-dose vancomycin for sustained cure of C difficile infection, and, to our knowledge, extended-pulsed fidaxomicin recurrence rates in this study are the lowest observed in a randomised clinical trial of antibiotic treatment for C difficile infection., Funding: Astellas Pharma, Inc., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

For the last few decades, multidrug resistance has become an increasing concern for both Gram-positive and Gram-negative bacteria. The number of new molecules has dramatically decreased and antibiotic resistance is now a priority in the international community. Facing this new threat, a large number of new as well as "old" solutions are now being discussed in the medical community to propose an alternative to antibiotic treatments. A first option is to potentiate the effect of existing molecules through combinations to circumvent the individual molecule resistance. The second option is to neutralise either the infectious agent itself or its by-products using specific antibodies. A third option is to use the pathogen signaling mechanism and inhibit the production of virulence factor through quorum sensing inhibition. A fourth pathway would be to interact with the patient's microbiota using either probiotics or faecal transplantation to modulate the innate immune response and improve response to the infectious challenge, but also to act directly against colonisation by resistant bacteria by replacing the flora with susceptible strains. The last option is to target the bacteria using phage therapy. Phages are natural viruses that specifically infect target bacteria independently of any antibiotic-susceptibility profile. In this review, we will discuss each of these options and provide the scientific rationale and the available clinical data. In the majority of cases, these treatments represent an interesting approach but not the ultimate solution to multiresistance. Well-performed clinical trials are still missing and the major priority remains to promote good use and appropriate stewardship of antibiotics to decrease resistance.

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., (© The Japanese Society for Immunology. 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: Two randomized controlled trials (RCTs) showed the non-inferiority of fidaxomicin compared with vancomycin for Clostridium difficile infection (CDI) treatment and its superiority regarding recurrence rate. The aim of this study was to evaluate fidaxomicin's efficacy in clinical practice., Methods: This single-center prospective cohort study included hospitalized patients treated with fidaxomicin for CDI. Demographic, clinical and biological data were collected. Primary outcome was efficacy of fidaxomicin (clinical cure, recurrence and global cure) at 10 weeks. Secondary outcome was efficacy among different subgroups., Results: Ninety-nine patients were included: 42 severe CDI, 16 complicated CDI and 41 recurrent CDI. Rates of clinical cure, recurrence and global cure were 87, 15 and 59%, respectively. Subgroup analysis showed a higher recurrence rate for patients with recurrent CDI compared with first episode (8 vs. 26%; p = 0.04). Binary toxin was associated with severe/complicated CDI (80 vs. 50%; p < 0.01) and recurrence (32 vs. 7%; p < 0.01). Fidaxomicin was used as a first line for 83% of the patients with recurrence and for only 52% of first episodes even though 86% had recurrence's risk factors., Conclusion: Compared with RCTs, fidaxomicin in real world is used for patients with more severe and recurrent CDI, but clinical cure and recurrence rates were similar. Comparative studies are needed in these specific subgroups. Our data also illustrate clinicians' difficulty to define a "patient at risk for recurrence" among the first episodes. Finally, we showed that binary toxin could be important in the screening for severity and recurrence risks.

Bacterial pathogens often subvert the innate immune system to establish a successful infection. The direct inhibition of downstream components of innate immune pathways is particularly well documented but how bacteria interfere with receptor proximal events is far less well understood. Here, we describe a Toll/interleukin 1 receptor (TIR) domain-containing protein (PumA) of the multi-drug resistant Pseudomonas aeruginosa PA7 strain. We found that PumA is essential for virulence and inhibits NF-κB, a property transferable to non-PumA strain PA14, suggesting no additional factors are needed for PumA function. The TIR domain is able to interact with the Toll-like receptor (TLR) adaptors TIRAP and MyD88, as well as the ubiquitin-associated protein 1 (UBAP1), a component of the endosomal-sorting complex required for transport I (ESCRT-I). These interactions are not spatially exclusive as we show UBAP1 can associate with MyD88, enhancing its plasma membrane localization. Combined targeting of UBAP1 and TLR adaptors by PumA impedes both cytokine and TLR receptor signalling, highlighting a novel strategy for innate immune evasion., (© 2017 The Authors. Published under the terms of the CC BY 4.0 license.)

Background: Nasendoscopes are widely used in the outpatient ENT setting. Their reprocessing requires high-level disinfection (HLD). Recently, a wiping procedure using chlorine dioxide (ClO 2 ) has been proposed as an alternative to HLD traditional procedures., Objective: To assess the effectiveness of the HLD wiping procedure versus soaking procedure on a contaminated nasendoscope., Method: A nasendoscope was contaminated with four strains of bacteria and Bacillus subtilis spores. After HLD either with the wiping procedure or with the soaking procedure (PA), the reduction of the initial contamination was determined., Findings: The wiping procedure with ClO 2 displayed more than 5 log reduction for vegetative bacteria after 30 s contact time (CT) and 4 log reduction on B. subtilis spores after 2 min CT. The soaking procedure with PA displayed similar results on planktonic bacteria after 10 min CT but the log reduction of B. subtilis remained below 4., Conclusion: The ClO 2 wiping procedure showed bactericidal and sporicidal efficacy on a contaminated nasendoscope in a shorter time compared to the PA soaking procedure. Thus, ClO 2 wiping procedure might be considered as an alternative to the traditional HLD procedure for nasendoscopes., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

We have previously shown that the eukaryotic C-type natriuretic peptide hormone (CNP) regulates Pseudomonas aeruginosa virulence and biofilm formation after binding on the AmiC sensor, triggering the amiE transcription. Herein, the involvement of the aliphatic amidase AmiE in P. aeruginosa virulence regulation has been investigated. The proteome analysis of an AmiE over-producing strain (AmiE + ) revealed an expression change for 138 proteins, including some that are involved in motility, synthesis of quorum sensing compounds and virulence regulation. We observed that the AmiE + strain produced less biofilm compared to the wild type, and over-produced rhamnolipids. In the same line, AmiE is involved in P. aeruginosa motilities (swarming and twitching) and production of the quorum sensing molecules N-acyl homoserine lactones and Pseudomonas Quinolone Signal (PQS). We observed that AmiE overproduction reduced levels of HCN and pyocyanin causing a decreased virulence in different hosts (i.e. Dictyostelium discoideum and Caenorhabditis elegans). This phenotype was further confirmed in a mouse model of acute lung infection, in which AmiE overproduction resulted in an almost fully virulence decrease. Taken together, our data suggest that, in addition to its role in bacterial secondary metabolism, AmiE is involved in P. aeruginosa virulence regulation by modulating pilus synthesis and cell-to-cell communication.

Background: Clostridium difficile infection (CDI) is characterized by high rates of recurrence, resulting in substantial health care costs. The aim of this study was to analyze the cost-effectiveness of treatments for the management of second recurrence of community-onset CDI in France., Methods: We developed a decision-analytic simulation model to compare 5 treatments for the management of second recurrence of community-onset CDI: pulsed-tapered vancomycin, fidaxomicin, fecal microbiota transplantation (FMT) via colonoscopy, FMT via duodenal infusion, and FMT via enema. The model outcome was the incremental cost-effectiveness ratio (ICER), expressed as cost per quality-adjusted life year (QALY) among the 5 treatments. ICERs were interpreted using a willingness-to-pay threshold of €32,000/QALY. Uncertainty was evaluated through deterministic and probabilistic sensitivity analyses., Results: Three strategies were on the efficiency frontier: pulsed-tapered vancomycin, FMT via enema, and FMT via colonoscopy, in order of increasing effectiveness. FMT via duodenal infusion and fidaxomicin were dominated (i.e. less effective and costlier) by FMT via colonoscopy and FMT via enema. FMT via enema compared with pulsed-tapered vancomycin had an ICER of €18,092/QALY. The ICER for FMT via colonoscopy versus FMT via enema was €73,653/QALY. Probabilistic sensitivity analysis with 10,000 Monte Carlo simulations showed that FMT via enema was the most cost-effective strategy in 58% of simulations and FMT via colonoscopy was favored in 19% at a willingness-to-pay threshold of €32,000/QALY., Conclusions: FMT via enema is the most cost-effective initial strategy for the management of second recurrence of community-onset CDI at a willingness-to-pay threshold of €32,000/QALY., Competing Interests: The authors of this manuscript have read the journal's policy and have the following competing interests: TG reports personal fees from Astellas and MSD, outside the submitted work. All authors report no competing interests relevant to this article. This does not alter our adherence to PLOS ONE policies on sharing data and materials.