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OBJECTIVE: Yersinia pseudotuberculosis causes ileitis and mesenteric lymphadenitis by mainly invading the Peyer’s patches that are positioned in the terminal ileum. Whereas toll-like-receptor 2 (TLR2) controls mucosal inflammation by detecting certain microbiota-derived signals, its exact role in protecting Peyer’s patches against bacterial invasion has not been defined. DESIGN: Wild-type, Tlr2-, Nod2- and MyD88-deficient animals were challenged by Y pseudotuberculosis via the oral or systemic route. The role of microbiota in conditioning Peyer’s patches against Yersinia through TLR2 was assessed by delivering, ad libitum, exogenous TLR2 agonists in drinking water to germ-free and streptomycin-treated animals. Bacterial eradication from Peyer’s patches was measured by using a colony-forming unit assay. Expression of cryptdins and the c-type lectin Reg3β was quantified by quantitative reverse transcriptase polymerase chain reaction analysis. RESULTS: Our data demonstrated that Tlr2-deficient mice failed to limit Yersinia dissemination from the Peyer’s patches and succumbed to sepsis independently of nucleotide-binding and oligomerisation domain 2 (NOD2). Recognition of both microbiota-derived and myeloid differentiation factor 88 (MyD88)-mediated elicitors was found to be critically involved in gut protection against Yersinia-induced lethality, while TLR2 was dispensable to systemic Yersinia infection. Gene expression analyses revealed that optimal epithelial transcript level of the anti-infective Reg3β requires TLR2 activation. Consistently, Yersinia infection triggered TLR2-dependent Reg3β expression in Peyer’s patches. Importantly, oral treatment with exogenous TLR2 agonists in germ-free animals was able to further enhance Yersinia-induced expression of Reg3β and to restore intestinal resistance to Yersinia. Lastly, genetic ablation of Reg3β resulted in impaired clearance of the bacterial load in Peyer’s patches. CONCLUSIONS: TLR2/REG3β is thus an essential component in conditioning epithelial defence signalling pathways against bacterial invasion. [ABSTRACT FROM AUTHOR]

In 2016, only 7% of French women had received an influenza vaccination during their pregnancy. In this vaccine-averse country, the possibility of reaching the rates of 50% observed in other countries remains unknown. To measure the rate of influenza vaccination in a French university maternity. To study its evolution and determinants over the last 5 years. Single-center observational study of all women who gave birth during March 2020 in this maternity. Comparison with rates observed in 2015 in the same conditions. Of the 337 women included in the study, 202 received a vaccination during pregnancy (59.9%). After logistic regression, the factors significantly associated with achieving vaccination were the offer of vaccination during pregnancy, odds ratio (ORa) 26.2 [7.0; 98.2]; previous vaccination, ORa 20.3 [9.6; 42.6]; high education level, ORa 2.9 [1.3; 6.2]; delivery of a CERFA government reimbursement form, ORa 2.5 [1.3; 4.8]; a vaccination offer made by a general practitioner, ORa 2.1 [1.0; 4.4] and not by a hospital midwife, ORa 0.3 [0.1; 0.6]. The rate of vaccination increased from 35% to 59.9% between 2015 and 2020 ( p  < .001), with a significant increase in the offer of vaccination during pregnancy (+14.6%) - especially by a general practitioner (+17.2%) - and in the rate of women with earlier vaccination (+13.6%). In France, vaccination rates above 50% are possible at a center level. A proposal of vaccination during pregnancy - especially by the general practitioner - seems to be a determining factor in this development.

Background: For the past three decades, researchers have proposed an association between bacterial vaginosis (BV) and preterm birth. This association has been questioned since treating BV with antibiotics during pregnancy hasn't led to a decreased risk of preterm birth., Objective: To re-assess the connection between BV and preterm birth by reviewing existing literature., Search Strategy: A systematic search was conducted on PubMed and Web of Science using the keywords "bacterial vaginosis" and "preterm birth" up to November 2020. The protocol followed PRISMA guidelines and was registered with PROSPERO (CRD42022337806)., Selection Criteria: Studies were included if they: 1) explored the link BV and preterm birth, 2) used diagnostic criteria based on Nugent, Amsel or Spiegel methods, 3) defined preterm birth at <37, 35, or 32 weeks, and 4) involved patients without impending preterm labor symptoms when sampled., Data Collection and Analysis: Data were extracted and analyzed by region, BV diagnosis method, study period, and quality score., Mains Results: A total of 28 studies were included in the analysis (comprising 50,466 patients). There was a significant link between BV and preterm birth, with an overall OR of 1.60 [95% CI, 1.36-1.89]. Heterogeneity was high (I²=67%). The elevated risk remained consistent across geographic areas, diagnostic procedures, study periods, and study quality scale (Newcastle-Ottawa score)., Conclusion: Our meta-analysis confirms the association between bacterial vaginosis and preterm birth. However, the connection appears to be weaker than previously documented. This observation may offer insight into the ineffectiveness of BV treatments in reducing preterm birth risk., Competing Interests: Declarations of interest None., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Carbapenemase-producing Enterobacterales (CPE) are spreading rapidly in hospital settings. Asymptomatic CPE gut colonisation may be associated with dysbiosis and gut-lung axis alterations, which could impact lung infection outcomes. In this study, in male C57BL/6JRj mice colonised by CPE, we characterise the resulting gut dysbiosis, and analyse the lung immune responses and outcomes of subsequent Pseudomonas aeruginosa lung infection. Asymptomatic gut colonisation by CPE leads to a specific gut dysbiosis and increases the severity of P. aeruginosa lung infection through lower numbers of alveolar macrophages and conventional dendritic cells. CPE-associated dysbiosis is characterised by a near disappearance of the Muribaculaceae family and lower levels of short-chain fatty acids. Faecal microbiota transplantation restores immune responses and outcomes of lung infection outcomes, demonstrating the involvement of CPE colonisation-induced gut dysbiosis in altering the immune gut-lung axis, possibly mediated by microbial metabolites such as short-chain fatty acids., (© 2023. The Author(s).)

We report in vivo development of cefiderocol (FDC) resistance among four sequential Pseudomonas aeruginosa clinical isolates ST244 recovered from a single patient, without exposure to FDC, which raises concern about the effectiveness of this novel drug. The first recovered P. aeruginosa isolate (P-01) was susceptible to FDC (2 μg/mL), albeit this MIC value was higher than that of a wild-type P. aeruginosa (0.12-0.25 μg/ml). The subsequent isolated strains (P-02, P-03, P-04) displayed increasing levels of FDC MICs (8, 16, and 64 μg/ml, respectively). Those isolates also showed variable and gradual increasing levels of resistance to most β-lactams tested in this study. Surprisingly, no acquired β-lactamase was identified in any of those isolates. Whole-genome sequence analysis suggested that this resistance was driven by multifactorial mechanisms including mutational changes in iron transporter proteins associated with FDC uptake, ampC gene overproduction, and mexAB-oprM overexpression. These findings highlight that a susceptibility testing to FDC must be performed prior to any prescription., (© 2022. The Author(s).)

Bacteria of the genus Achromobacter are environmental germs, with an unknown reservoir. It can become opportunistic pathogens in immunocompromised patients, causing bacteremia, meningitis, pneumonia, or peritonitis. In recent years, Achromobacter xylosoxidans has emerged with increasing incidence in patients with cystic fibrosis (CF). Recent studies showed that A. xylosoxidans is involved in the degradation of the respiratory function of patients with CF. The respiratory ecosystem of patients with CF is colonized by bacterial species that constantly fight for space and access to nutrients. The type VI secretion system (T6SS) empowers this constant bacterial antagonism, and it is used as a virulence factor in several pathogenic bacteria. This study aimed to investigate the prevalence of the T6SS genes in A. xylosoxidans isolated in patients with CF. We also evaluated clinical and molecular characteristics of T6SS-positive A. xylosoxidans strains. We showed that A. xylosoxidans possesses a T6SS gene cluster and that some environmental and clinical isolates assemble a functional T6SS nanomachine . A. xylosoxidans T6SS is used to target competing bacteria, including other CF-specific pathogens. Finally, we demonstrated the importance of the T6SS in the internalization of A. xylosoxidans in lung epithelial cells and that the T6SS protein Hcp is detected in the sputum of patients with CF. Altogether, these results suggest for the first time a role of T6SS in CF-lung colonization by A. xylosoxidans and opens promising perspective to target this virulence determinant as innovative theranostic options for CF management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Le Goff, Vastel, Lebrun, Mansuelle, Diarra, Grandjean, Triponney, Imbert, Gosset, Dessein, Garnier and Durand.)

Many countries with a high perinatal level have started a policy of vaccination of pregnant women against pertussis. To date, France has not chosen this policy. The objective was to review knowledge on pertussis mortality in infants. Compare the strategies available to protect the infant before his first vaccination, scheduled for two months of age. We proceeded to a litterature analysis, from January 1998 to 2021. Search by the following keywords used ; "Whooping cough, vaccination, pregnancy, strategy, cocooning", on the scientific basis of "Pubmed", as well as French and foreign vaccination recommendations. Currently 90% of whooping cough deaths are concerning infants under six months of age and this mortality represents 2% of mortality in the first year of life. Vaccination at birth is not effective. The cocooning strategy, which consists of vaccinating those around the child, is expensive and difficult to implement. A systematic vaccination policy for pregnant women is effective and reasonably expensive when compared to the cocooning strategy. In England, it was recently accompanied by a 78% reduction in confirmed cases of pertussis in infants under six months of age. In conclusion, compared to cocooning strategy, pertussis vaccination of pregnant women appears more effective and cost-effective, and this with each pregnancy., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Colonization resistance by gut microbiota is a fundamental phenomenon in infection prevention and control. Hospitalized patients may be exposed to multi-drug-resistant bacteria when hand hygiene compliance among healthcare workers is not adequate. An additional layer of defence is provided by the healthy gut microbiota, which helps clear the exogenous bacteria and acts as a safety net when hand hygiene procedures are not followed. This narrative review focuses on the role of the gut microbiota in colonization resistance against multi-drug-resistant bacteria, and its implications for infection control. The review discusses the underlying mechanisms of colonization resistance (direct or indirect), the concept of resilience of the gut microbiota, the link between the antimicrobial spectrum and gut dysbiosis, and possible therapeutic strategies. Antimicrobial stewardship is crucial to maximize the effects of colonization resistance. Avoiding unnecessary antimicrobial therapy, shortening the antimicrobial duration as much as possible, and favouring antibiotics with low anti-anaerobe activity may decrease the acquisition and expansion of multi-drug-resistant bacteria. Even after antimicrobial therapy, the resilience of the gut microbiota often occurs spontaneously. Spontaneous resilience explains the existence of a window of opportunity for colonization of multi-drug-resistant bacteria during or just after antimicrobial therapy. Strategies favouring resilience of the gut microbiota, such as high-fibre diets or precision probiotics, should be evaluated., (Copyright © 2021 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Chlamydia trachomatis (CT) is the most common sexually transmitted bacterial infection worldwide. It is asymptomatic in most cases and mainly affects young women, with potential long term sequelae (pelvic inflammatory disease, tubal infertility, obstetric complications). The impact on male fertility is controversial. Screening methods as well as antibiotics use have recently been reassessed due to resistance phenomena and the negative effect on the urogenital microbiota. Positive CT serology may be indicative of tuboperitoneal pathology, which may not be noticed on hysterosalpingography. New research on single-nucleotide polymorphisms (SNPs) aims to establish a patient profile at higher risk of infectious tubal damage due to CT. CT seropositivity is also associated with decreased spontaneous pregnancy rates and is a predictive factor for obstetrical complications., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

A recently developed, automated blood culture system and medium improve the time-to-positivity (TTP) for bacteremia. However, there have thus far been no genus-level analyses using this novel system. We evaluated and compared the changes in blood culture TTP between two systems: BacT/Alert 3D with a blood culture medium containing activated charcoal versus the more recent BacT/Alert Virtuo with a blood culture medium containing polymeric beads. This before-and-after study included blood cultures collected between July 2010 and April 2014 (3D, activated charcoal) and between July 2015 and April 2018 (Virtuo, polymeric beads). A total of 554,732 blood cultures were included, 267,935 (48.30%) during the first period and 286,797 (51.70%) during the second period. Overall, 55,611 (10.02%) tested positive for at least one microorganism. The incubation of the blood culture medium in the Virtuo system was associated with reduced TTP for the most prevalent bacteria, those representing 91.72% (n=51,006) of all the positive blood cultures. The median TTP was reduced by 0.99 h for Staphylococcus, Enterococcus, Streptococcus, Pseudomonadales, and most of the genera within the order Enterobacterales (except the family Morganellaceae). However, strictly anaerobic bacteria belonging to the genus Bacteroides, representing 0.85% (n=474) of all positive blood cultures, were detected 4.53 h later using the Virtuo system. Virtuo was associated with a shorter TTP for most bacteria, but this improvement was heterogeneous to the genus level.

Bacterial vaginosis (BV) diagnosis in pregnancy is based on the Nugent score, which consists of semiquantitation of bacterial morphotypes. Limited data exist concerning molecular-based diagnosis in asymptomatic pregnant women. Using high-throughput quantitative PCR, 34 microorganisms were screened in asymptomatic pregnant women and compared with the Nugent score. Three-hundred and four vaginal samples had a Nugent score <7 (69.9%) and 131, a Nugent score ≥7 (30.1%), consistent with BV. More pregnant women with BV share Atopobiumvaginae, bacterial vaginosis associated bacteria-2, Gardnerella spp., Mobiluncus curtisii, Mo. mulieris, Mycoplasma hominis, Ureaplasma urealyticum, Prevotella bivia, Megasphaera 1, and Megasphaera 2 in their vaginal sample. Fewer pregnant women with BV share Lactobacillus crispatus, L. gasseri, L. jensenii, and Enterococcus faecalis in their vaginal sample (P < 0.001). Classification and regression tree analysis was performed to determine which combinations of detected bacteria optimally diagnose BV in this population. A set of only four bacteria of 34 microorganisms (A. vaginae, Gardnerella spp., L. crispatus, and P. bivia) was the best combination to identify BV in a cohort of asymptomatic pregnant women, with a sensitivity of 77.1%, and specificity of 97.0% compared with the Nugent score. The quantitative PCR in the present study responds to the limits of the Nugent score by implementing an easily reproducible quantitative assay to assess the absence of BV in pregnancy., (Copyright © 2021 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

This study aimed to analyse the frequency of occurrence of spontaneous decolonization in intensive care unit patients colonized by extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) in order to assess the added value of continuing weekly ESBL-E rectal carriage screening in these patients. In total, 49,468 weekly rectal screening samples taken from 20,846 patients over 12 years were included. Among the 4280 ESBL-E carriers, only 109 patients (2.5%) could be considered decolonized at the end of their hospitalization with at least three consecutive negative samples. Overall, 7957 samples (16.1%) were requested for patients already identified as ESBL-E carriers. Avoiding unnecessary weekly screening following positive ESBL-E colonization results could decrease nursing and laboratory work loads., (Copyright © 2020 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

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.

Exacerbations are a main characteristic of asthma. In childhood, the risk is increasing with severity. Exacerbations are a strong phenotypic marker, particularly of severe and therapy-resistant asthma. These early-life events may influence the evolution and be involved in lung function decline. In children, asthma attacks are facilitated by exposure to allergens and pollutants, but are mainly triggered by microbial agents. Multiple studies have assessed immune responses to viruses, and to a lesser extend bacteria, during asthma exacerbation. Research has identified impairment of innate immune responses in children, related to altered pathogen recognition, interferon release, or anti-viral response. Influence of this host-microbiota dialog on the adaptive immune response may be crucial, leading to the development of biased T helper (Th)2 inflammation. These dynamic interactions may impact the presentations of asthma attacks, and have long-term consequences. The aim of this review is to synthesize studies exploring immune mechanisms impairment against viruses and bacteria promoting asthma attacks in children. The potential influence of the nature of infectious agents and/or preexisting microbiota on the development of exacerbation is also addressed. We then discuss our understanding of how these diverse host-microbiota interactions in children may account for the heterogeneity of endotypes and clinical presentations. Finally, improving the knowledge of the pathophysiological processes induced by infections has led to offer new opportunities for the development of preventive or curative therapeutics for acute asthma. A better definition of asthma endotypes associated with precision medicine might lead to substantial progress in the management of severe childhood asthma., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Preschool asthma/recurrent wheeze is a heterogeneous condition. Different clinical phenotypes have been described, including episodic viral wheeze (EVW), severe intermittent wheeze (SIW), and multiple-trigger wheeze (MTW)., Objective: To compare clinical, viral, and inflammatory/immune profiling at exacerbation between MTW, SIW, and EVW phenotypes., Methods: Multicenter, prospective, observational cohort (VIRASTHMA-2). Children (1-5 years) with preschool asthma were enrolled during hospitalization for a severe exacerbation. History and anamnestic data, plasma, and nasal samples were collected at exacerbation (T1) and at steady state, 8 weeks later (T2), and sputum samples were collected at T1., Results: A total of 147 children were enrolled, 37 (25%) had SIW, 18 (12.2%) EVW, and 92 (63%) MTW. They were atopic (47%), exposed to mold (22%) and cigarette smoke (50%), and prone to exacerbations (≥2 in the previous year in 70%). At exacerbation, at least one virus was isolated in 94% and rhinovirus in 75%, with no difference between phenotypes. Children with MTW and SIW phenotypes displayed lower plasma concentrations of IFN-γ (P = .002), IL-5 (P = .020), TNF-α (P = .038), IL-10 (P = .002), IFN-β (P = .036), and CXCL10 (P = .006) and lower levels of IFN-γ (P = .047) in sputum at exacerbation than children with EVW. At T2, they also displayed lower plasma levels of IFN-γ (P = .045) and CXCL10 (P = .013)., Conclusion: Among preschool asthmatic children, MTW and SIW, prone to exacerbations, display lower systemic levels of Th1, Th2 cytokines, pro- and anti-inflammatory cytokines, and antiviral responses during severe virus-induced exacerbation., (© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.)

Introduction: Although influenza can lead to adverse outcomes during pregnancy, the level of influenza vaccine coverage among pregnant women remains very low. According to the literature, a high level of knowledge about influenza disease and the influenza vaccine is one of the main determinants of vaccination coverage. The objective of the present study was to describe pregnant women's level of knowledge of these topics and to identify any corresponding determinants., Material and Methods: A prospective, observational, hospital-based study of women having given birth in our university medical centre during the 2014-2015 influenza season. Data were collected through a self-questionnaire or extracted from medical records. Determinants of highest knowledge were identified using logistic regression., Results: Of the 2069 women included in the study, 827 (40%) did not know that influenza can lead to severe adverse outcomes for the mother, and 960 (46%) did not know about possible severe adverse outcomes for the baby. Two hundred and one women (9.8%) stated that the vaccine was "contraindicated" or "unnecessary" during pregnancy. Only 205 women (17%) had been vaccinated during a previous pregnancy. Determinants of the highest level of knowledge were age over 24, a high educational level, previous influenza vaccination, nulliparity, and the recommendation of vaccination by a healthcare professional., Conclusions: Recommending vaccination during pregnancy appears to increase knowledge about influenza and its vaccine among pregnant women., Competing Interests: The authors have declared that no competing interests exist.

Clostridium spp. are recovered from 25% of the blood culture positive with anaerobes. However, the clinical relevance of Clostridium bacteremia has been controverted in the literature, particularly for C. perfringens. We aimed to evaluate the clinical relevance of Clostridium bacteremia, either due to C. perfringens or other Clostridium species, and to identify the risk factors of mortality in these patients. A retrospective cohort study was conducted from January 2010 to April 2018. All the patients with at least one blood culture positive with any Clostridium species were included. Eighty-one patients with a least one blood culture positive with any Clostridium species were included. Seventy patients (86.4%) fulfilled the criteria for clinically relevant bacteremia. Bacteremia due to C. perfringens tended to be less clinically relevant than other Clostridium species but this was not statistically significant (76% vs 91.2%, P = 0.09). In case of clinically relevant bacteremia, the 30-day mortality rate was 31.4%. In multivariate analysis, adequate empiric antimicrobial therapy was significantly associated with survival (P = 0.03). In conclusion, bacteremia due to C. perfringens or other Clostridium species is usually clinically relevant. This finding was also supported by an improved survival at 30 days when adequate empiric antimicrobial therapy was administered., Competing Interests: Declaration of competing interest No conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Although vaccination of pregnant women against influenza is recommended, the vaccination rate remains low. We conducted a study to identify determinants of influenza vaccination uptake in pregnancy in order to identify strategies to improve seasonal influenza vaccination rates., Methods: Prospective observational hospital-based study in the French hospital performing the highest number of deliveries, located in the city of Lille, among all women who had given birth during the 2014-2015 influenza season. Data were collected through a self-completed questionnaire and from medical files. The vaccination uptake was self-reported. Determinants of vaccination uptake were identified using logistic regression analysis., Results: Of the 2045 women included in the study, 35.5% reported that they had been vaccinated against influenza during their pregnancy. The principal factors significantly associated with greater vaccination uptake were previous influenza vaccination (50.9% vs 20.2%, OR 4.1, 95% CI 3.1-5.5), nulliparity (41.0% vs 31.3%, OR 2.5, 95% CI 1.7-3.7), history of preterm delivery < 34 weeks (43.4% vs 30.3%, OR 2.3, 95% CI 1.1-4.9), the mother's perception that the frequency of vaccine complications for babies is very low (54.6% vs 20.6%, OR 1.1, 95% CI 0.5-2.2), the mother's good knowledge of influenza and its vaccine (61.7% vs 24.4%, OR 3.1, 95% CI 2.2-4.4), hospital-based prenatal care in their first trimester of pregnancy (55.0% vs 30.2%, OR 2.1, 95% CI 1.2-3.7), vaccination recommendations during pregnancy by a healthcare worker (47.0% vs 2.7%, OR 18.8, 95% CI 10.0-35.8), receipt of a vaccine reimbursement form (52.4% vs 18.6%, OR 2.0, 95% CI 1.5-2.7), and information from at least one healthcare worker about the vaccine (43.8% vs 19.1%, OR 1.8, 95% CI 1.3-2.6)., Conclusions: Our findings suggest that in order to increase flu vaccination compliance among pregnant women, future public health programmes must ensure cost-free access to vaccination, and incorporate education about the risks of influenza and the efficacy/safety of vaccination and clear recommendations from healthcare professionals into routine antenatal care.

Clostridium ventriculi (formerly Sarcina ventriculi) is a Gram-positive, obligate anaerobic coccus. Human infections due to this bacterium have rarely been reported, its involvement in the development of gastric ulcers and perforation has been suggested. We present a case of bacteremia due to C. ventriculi following acute colonic pseudo-obstruction., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Pneumococcal meningitis (PM) is a serious disease that can rarely recur at a later time after the initial episode., Methods: A retrospective multicenter case-control study was conducted with data for children 18 years of age or younger obtained from the National Observatory of Bacterial Meningitis in Children between January 2001 and September 2015. Cases were all patients with RPM. Each case was matched with 2 randomized controls with a single PM episode in the year of the first episode of PM in the case and born the same year. Case and control data were compared., Results: Among the 1634 PM episodes in children 18 years of age or younger, 24 (1.5%) children had RPM. RPM cases were significantly less frequent than single PM cases in winter (27% vs. 48%; P=0.03) and showed significantly less concomitant ear, nose and throat infections when considering the first episode (30% vs. 56%, P = 0.04) and all episodes (28% vs. 56%, P < 0.01). Cerebrospinal fluid leakage was frequent in RPM cases versus controls (83% vs. 10%, P < 0.01), including 25% discovered after the third PM episode. Immune deficiency was absent in cases and present in 15% of controls. Cases and controls did not differ in death rate or neurologic outcome., Conclusions: RPM is rare in children. Cerebrospinal fluid leakage must be considered.

Objective: To describe and analyze the differences between infections in children with febrile neutropenia (FN) treated for solid tumor or blood cancer., Methods: A prospective study included all episodes of FN in children from April 2007 to April 2016 in 2-pediatric cancer centers in France. Medical history, clinical and laboratory data available at admission and final microbiological data were collected. The proportion of FN, severe infection, categories of microorganisms and outcomes were compared between the two groups. The presumed gateway of the infection was a posteriori considered and evaluated., Results: We analyzed 1197 FN episodes (mean age: 8 years). 66% of the FN episodes occurred in children with blood cancer. Severe infections were identified in 23.4% of episodes overall. The rate of severe infection (28.4% vs. 10.4%), types of microorganisms and the need for a management in intensive care unit (2.6% vs. 0.5%) was significantly different between children with blood cancer and solid tumor. Digestive or respiratory presumed gateway of the infections was less frequent for patients with solid tumor., Conclusion: Given these important microbiological and clinical differences, it may be appropriate to consider differently the risk of severe infection in these two populations and therefore the management of FN., (Copyright © 2019 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

While antibiotic use is a risk factor of carbapenemase-producing Enterobacteriaceae (CPE) acquisition, the importance of timing of antibiotic administration relative to CPE exposure remains unclear. In a murine model of gut colonization by New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae , a single injection of clindamycin within at most 1 week before or after CPE exposure induced colonization persisting up to 100 days. The timing of antibiotic administration relative to CPE exposure may be relevant to infection control and antimicrobial stewardship approaches., (Copyright © 2019 American Society for Microbiology.)

Postpartum endometritis accounts for 2% of postpartum infections in developed countries. In France, 2.3% of deaths are attributed to puerperal infections. The most important risk factor is cesarean delivery, especially if it is done after the start of labor. Bacteria of the vaginal microbiota are associated with postpartum endometritis. Symptoms are abdomino-pelvic pain, hyperthermia and abnormal lochia. The diagnosis is confirmed by uterine mobilization pain. The first-line antibiotic therapy is amoxicillin-clavulanic acid 3 to 6 grams per day depending on the weight, intravenously or orally. In case of impossibility to use penicillins (anaphylaxis for example), the combination of clindamycin 600mg×4/d plus gentamicin 5mg/kg×1/d may be use, it must be a specialized decision in case of maternal breastfeeding. The treatment is continued until obtaining 48hours of apyrexia and the disappearance of pelvic pain. In case of persistence of fever and/or pelvic pain after 72hours of antibiotic therapy, pelvic imaging should be performed for placental retention, septic thrombophlebitis, deep abscess or any other surgical complication and eliminate differential diagnoses. It is important to highlight the difficulties of interpreting endo-uterine images in ultrasound. Hypocoagulant heparin therapy should be started in case of septic thrombophlebitis for 6 weeks, or longer if there are complications such as embolism or thrombotic risk factors. Regarding prevention, during a caesarean section, a vaginal swab with iodinated polividone or chlorhexidine is recommended before caesarean if possible, and extraction of the placenta must be spontaneous., (Copyright © 2019 CNGOF, SPILF. Published by Elsevier Masson SAS.. All rights reserved.)

Tetraphenylethylene (TPE) is fluorescent through aggregation induced emission (AIE) in water. Herein, TPE was used as the core of glycoclusters that target the bacterial lectins LecA and LecB of Pseudomonas aeruginosa. Synthesis of these TPE-based glycoclusters was accomplished by using azide-alkyne "click" chemistry. The AIE properties of the resulting glycoclusters could be readily verified, but imaging could not be pursued due to the overlap of the fluorescence signals from cells and bacteria. Nonetheless, the glycoclusters displayed nanomolar affinities toward LecA and LecB. Further evaluation in a cell-based anti-adhesive assay highlighted a limited decrease in adhesion (20%) for the fucosylated glycocluster. This confirmed that these TPE-based glycoclusters are indeed LecA and LecB high-affinity ligands. Nevertheless, the hypotheses involving their application in imaging or anti-adhesive therapy could not be verified.

Background: Preterm delivery during pregnancy (<37 weeks' gestation) is a leading cause of perinatal mortality and morbidity. Treating bacterial vaginosis during pregnancy can reduce poor outcomes, such as preterm birth. We aimed to investigate whether treatment of bacterial vaginosis decreases late miscarriages or spontaneous very preterm birth., Methods: PREMEVA was a double-blind randomised controlled trial done in 40 French centres. Women aged 18 years or older with bacterial vaginosis and low-risk pregnancy were eligible for inclusion and were randomly assigned (2:1) to three parallel groups: single-course or triple-course 300 mg clindamycin twice-daily for 4 days, or placebo. Women with high-risk pregnancy outcomes were eligible for inclusion in a high-risk subtrial and were randomly assigned (1:1) to either single-course or triple-course clindamycin. The primary outcome was a composite of late miscarriage (16-21 weeks) or spontaneous very preterm birth (22-32 weeks), which we assessed in all patients with delivery data (modified intention to treat). Adverse events were systematically reported. This study is registered with ClinicalTrials.gov, number NCT00642980., Findings: Between April 1, 2006, and June 30, 2011, we screened 84 530 pregnant women before 14 weeks' gestation. 5630 had bacterial vaginosis, of whom 3105 were randomly assigned to groups in the low-risk trial (n=943 to receive single-course clindamycin, n=968 to receive triple-course clindamycin, and n=958 to receive placebo) or high-risk subtrial (n=122 to receive single-course clindamycin and n=114 to receive triple-course clindamycin). In 2869 low-risk pregnancies, the primary outcome occurred in 22 (1·2%) of 1904 participants receiving clindamycin and 10 (1·0%) of 956 participants receiving placebo (relative risk [RR] 1·10, 95% CI 0·53-2·32; p=0·82). In 236 high-risk pregnancies, the primary outcome occurred in 5 (4·4%) participants in the triple-course clindamycin group and 8 (6·0%) participants in the single-course clindamycin group (RR 0·67, 95% CI 0·23-2·00; p=0·47). In the low-risk trial, adverse events were more common in the clindamycin groups than in the placebo group (58 [3·0%] of 1904 vs 12 [1·3%] of 956; p=0·0035). The most commonly reported adverse event was diarrhoea (30 [1·6%] in the clindamycin groups vs 4 [0·4%] in the placebo group; p=0·0071); abdominal pain was also observed in the clindamycin groups (9 [0·6%] participants) versus none in the placebo group (p=0·034). No severe adverse event was reported in any group. Adverse fetal and neonatal outcomes did not differ significantly between groups in the high-risk subtrial., Interpretation: Systematic screening and subsequent treatment for bacterial vaginosis in women with low-risk pregnancies shows no evidence of risk reduction of late miscarriage or spontaneous very preterm birth. Use of antibiotics to prevent preterm delivery in this patient population should be reconsidered., Funding: French Ministry of Health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Pseudomonas aeruginosa infections are challenging due to intrinsic and acquired resistance mechanisms. We report here the draft genome sequences of two multidrug-resistant strains-PAL0.1, isolated from the airways of an intensive care unit (ICU) patient with ventilator-associated pneumonia, and PAL1.1, isolated from blood cultures of an ICU patient with sepsis.

Carbapenemase-producing Klebsiella pneumoniae represents an emerging public health issue. Here, we present the draft whole-genome sequences of K. pneumoniae clinical strains KPL0.1 (OXA-48 carbapenemase) and KPL0.2 (NDM-1 carbapenemase). These genome sequences should help in investigating pathophysiological mechanisms of digestive colonization or infection with these highly resistant bacteria.

Objective: To evaluate clinical practices for ESBL-producing urinary tract infection (UTI) in France., Methods: We performed an observational, retrospective, cross-sectional, hospital-based study in 22 pediatric departments of university or secondary care hospitals. We collected data of the last five patients presenting with ESBL-producing UTI in 2012 and the physicians' therapeutic approach to two case vignettes of acute non-septic ESBL-producing pyelonephritis (7-month-old girl) and cystitis (30-month-old girl). The adequacy of the therapeutic decision was analyzed by a panel of independent infectious disease experts., Results: A total of 80 case patients of ESBL-producing UTI were collected: 54 with acute pyelonephritis (mean age: 28 months, female: 66%), of whom 98% received an intravenous ESBL-adapted antibiotic treatment and 55% a two-drug antibiotic therapy. Carbapenems were used in 56% of cases and aminoglycosides in 36%. Of the 26 cystitis patients (mean age: 5 years, female: 73%), 85% were treated with antibiotics, including three intravenously (carbapenems=2). For the case vignettes, physicians (n=85) would have treated the pyelonephritis patient with carbapenems (76%) and/or aminoglycosides (68%); 71% would have used a two-drug antibiotic treatment. The cystitis patient would have been treated intravenously by 29% of physicians; 8% would have used a two-drug antibiotic treatment, 16% would have prescribed carbapenems, and 11% aminoglycosides. Antibiotic treatments were deemed appropriate in 37% of cases., Conclusions: Antimicrobial treatment for ESBL-producing UTI greatly varies, and carbapenems are excessively prescribed. Specific guidelines for ESBL infections are required., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The synthesis of eight perylenediimide-based glycoclusters was readily performed from hexa- and tetra-propargylated cores through azide-alkyne "click" conjugation. Variations in the carbohydrate epitope (Glc, Gal, Man, Fuc) and the linker arm provided molecular diversity. Interactions with LecA and LecB, two proteins involved in the adhesion of Pseudomonas aeruginosa to host tissues, were evaluated by microcalorimetry (ITC). In both cases high affinities were obtained with K d values in the nanomolar range. Further evaluation of their anti-adhesive properties using cultured epithelial cells demonstrated their potent anti-adhesive activities against Pseudomonas aeruginosa with only 30-40% residual adhesion observed. The fluorescence properties of the PDI core were then investigated by confocal microscopy on cell-bacteria cultures. However, the red fluorescence signal of the PDI-based glycocluster was too weak to provide significant data. The present study provides another type of anti-adhesive glycocluster against bacterial infection with a large aromatic PDI core.

Objectives: Screening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults., Methods: Eligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening., Results: The study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively., Conclusion: PID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults., (Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

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.)

Background: Pseudomonas aeruginosa (Pa) is a Gram-negative bacteria frequently involved in healthcare-associated pneumonia with poor clinical outcome. To face the announced post-antibiotic era due to increasing resistance and lack of new antibiotics, new treatment strategies have to be developed. Immunomodulation of the host response involved in outcome could be an alternative therapeutic target in Pa-induced lung infection. Kynurenines are metabolites resulting from tryptophan catabolism and are known for their immunomodulatory properties. Pa catabolizes tryptophan through the kynurenine pathway. Interestingly, many host cells also possess the kynurenine pathway, whose metabolites are known to control immune system homeostasis. Thus, bacterial metabolites may interfere with the host's immune response. However, the kynurenine pathway in Pa, including functional enzymes, types and amounts of secreted metabolites remains poorly known. Using liquid chromatography coupled to mass spectrometry and different strains of Pa, we determined types and levels of metabolites produced by Pa ex vivo in growth medium, and the relevance of this production in vivo in a murine model of acute lung injury., Results: Ex vivo, Pa secretes clinically relevant kynurenine levels (μM to mM). Pa also secretes kynurenic acid and 3-OH-kynurenine, suggesting that the bacteria possess both a functional kynurenine aminotransferase and kynurenine monooxygenase. The bacterial kynurenine pathway is the major pathway leading to anthranilate production both ex vivo and in vivo. In the absence of the anthranilate pathway, the kynurenine pathway leads to kynurenic acid production., Conclusion: Pa produces and secretes several metabolites of the kynurenine pathway. Here, we demonstrate the existence of new metabolic pathways leading to synthesis of bioactive molecules, kynurenic acid and 3-OH-kynurenine in Pa. The kynurenine pathway in Pa is critical to produce anthranilate, a crucial precursor of some Pa virulence factors. Metabolites (anthranilate, kynurenine, kynurenic acid) are produced at sustained levels both ex vivo and in vivo leading to a possible immunomodulatory interplay between bacteria and host. These data may imply that pulmonary infection with bacteria highly expressing the kynurenine pathway enzymes could influence the equilibrium of the host's tryptophan metabolic pathway, known to be involved in the immune response to infection. Further studies are needed to explore the effects of these metabolic changes on the pathophysiology of Pa infection.

Background and Objectives: Infections caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) have become a major public health issue worldwide. Cefoxitin is a second-generation cephalosporin and is associated with a strong in vitro activity against ESBL., Patients and Methods: We conducted a prospective monocentric cohort study from 2012 to 2015 to evaluate the clinical efficacy and safety of cefoxitin in 15 patients treated for urinary tract infection (UTI) caused by ESBL-E, without any severity criteria., Results: We included 15 patients; 11 were male patients with defined risk factors for ESBL-E. Ten patients presented with male UTI, three with pyelonephritis, and two with cystitis. Escherichia coli was the predominant pathogen. All patients had a positive outcome with a good tolerance (a skin rash without any sign of severity was observed in one patient). Microbiological cure was obtained in 9 patients out of 10 at the end of treatment., Conclusion: Cefoxitin is an alternative treatment to carbapenems for urinary tract infections caused by ESBL-producing Enterobacteriaceae., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Objective: Two years after the French guidelines, the objective was to assess the feasibility and efficiency of ultrasound-guided trans-vaginal drainage of tubo-ovarian abscesses (TOA) and to study the responsible germs., Material and Methods: All the patients with a larger abscess than 20mm were included prospectively from May 2011 to July 2014 in the university hospital of Lille., Results: Sixty-nine drainages were performed among 50 patients. Success rate was 94%. No complication occurred. One germ was found in 55% of patients, the TOA was polymicrobian in 20% of cases., Conclusion: Ultrasound-guided trans-vaginal drainage of TOA is safe and effective with more than 90% of success rate., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on the incidence of pneumococcal meningitis (PM) in children is unknown. To determine this impact, a descriptive multicentre retrospective cohort study was conducted from 2008 to 2013 in northern France. All laboratory-confirmed PM in children aged <18 years in all hospitals of the area with paediatric units were included. Two independent databases were used for exhaustive identification of cases: medical plus laboratory records at each hospital and discharge codes. The corrected incidence of PM was determined by a capture-recapture analysis using these two databases. Sixty-two cases were found over the 6-year period. A decrease of the PM corrected incidence was observed in the global population (P = 0·07), significant only for children aged <2 years, from 11·9/100 000 in 2008 in 1·9/100 000 in 2013 [6·4 fold-decrease, 95% confidence interval (CI) 1·4-41, P = 0·01] between years 2008 and 2013. When comparing the pre- and post-PCV13 periods, this decrease was still statistically significant for children aged <2 years [7·32/100 000 (95% CI 4·39-10·25) to 2·78/100 000 (95% CI 0·96-4·60), P = 0·01]. Only three (5%) cases of PM caused by vaccine serotypes could have been prevented. After the introduction of the PCV13 vaccine, a decrease in the incidence of PM cases in children in northern France was observed.

Bacterial vaginosis (BV) is considered as a trigger for an inflammatory response that could promote adverse pregnancy outcome (APO). We hypothesized that BV-related inflammation could be counterbalanced by anti-inflammatory and mucosal homeostatic responses that could participate in pregnancy outcomes.A total of 402 vaginal self-samples from pregnant women in their first trimester were screened by Nugent score. In this population, we enrolled 23 pregnant women with BV but without APO, 5 pregnant women with BV and developing APO, 21 pregnant women with intermediate flora, and 28 random control samples from pregnant women without BV or APO.BV without APO in pregnant women was associated with 28-fold interleukin-8, 5-fold interleukin-10, and 40-fold interleukin-22 increases in expression compared to controls. BV associated with APO in pregnant women shared 4-fold increase in tumor necrosis factor, 100-fold decrease in interleukin-10, and no variation in interleukin-22 expressions compared to controls. Next-generation sequencing of vaginal microbiota revealed a shift from obligate anaerobic bacteria dominance in BV without APO pregnant women to Lactobacillus dominance microbiota in BV with APO.Our results show that the anti-inflammatory and mucosal homeostatic responses to BV may determine outcome of pregnancy in the setting of BV possibly through effects on the vaginal microbiota.

Introduction: Patients with advanced chronic obstructive pulmonary disease (COPD) are at risk for developing invasive pulmonary aspergillosis. A clinical algorithm has been validated to discriminate colonization from putative invasive pulmonary aspergillosis (PIPA) in Aspergillus-positive respiratory tract cultures of critically ill patients. We focused on critically ill patients with COPD who met the criteria for PIPA., Methods: This matched cohort study included critically ill patients with COPD from two university hospital intensive care units (ICUs). We studied the risk factors for PIPA as well as the impact of PIPA on short- and long-term outcomes. Whether PIPA was associated with a pattern of bacterial colonization and/or infection 6 months before and/or during ICU stay was assessed. In addition, antifungal strategies were reviewed., Results: Fifty cases of PIPA in critically ill patients with COPD in the ICU were matched with one hundred control patients with COPD. The ICU short- and the long-term (at 1 year) mortality were significantly increased in the PIPA group (p < 0.001 for all variables). PIPA was a strong independent risk factor for mortality in the ICU (odds ratio 7.44, 95 % confidence interval 2.93-18.93, p < 0.001) before vasopressor therapy, renal replacement therapy, and duration of mechanical ventilation. Before ICU admission, the use of corticosteroids and antibiotics significantly increased the risk of PIPA (p = 0.004 and p < 0.001, respectively). No significant difference in bacterial etiologic agents responsible for colonization and/or infection was found between the groups. Antifungal treatment was started in 64 % of PIPA cases, with a poor impact on the overall outcome., Conclusions: PIPA was a strong death predictor in critically ill patients with COPD. The use of corticosteroids and antibiotics before ICU admission was a risk factor for PIPA. PIPA was not associated with a specific bacterial pattern of colonization or infection. Prompting antifungal treatment in critically ill patients with COPD who have PIPA may not be the only factor involved in prognosis reversal.

The murine norovirus (MNV) is a recently discovered mouse pathogen, representing the most common contaminant in laboratory mouse colonies. Nevertheless, the effects of MNV infection on biomedical research are still unclear. We tested the hypothesis that MNV infection could alter immune response in mice with acute lung infection. Here we report that co-infection with MNV increases survival of mice with Pseudomonas aeruginosa acute lung injury and decreases in vivo production of pro-inflammatory cytokines. Our results suggest that MNV infection can deeply modify the parameters studied in conventional models of infection and lead to false conclusions in experimental models.

The export of bacterial toxins across the bacterial envelope requires the assembly of complex, membrane-embedded protein architectures. Pseudomonas aeruginosa employs type III secretion (T3S) injectisome to translocate exotoxins directly into the cytoplasm of a target eukaryotic cell. This multi-protein channel crosses two bacterial membranes and extends further as a needle through which the proteins travel. We show in this work that PscI, proposed to form the T3S system (T3SS) inner rod, possesses intrinsic properties to polymerize into flexible and regularly twisted fibrils and activates IL-1β production in mouse bone marrow macrophages in vitro. We also found that point mutations within C-terminal amphipathic helix of PscI alter needle assembly in vitro and T3SS function in cell infection assays, suggesting that this region is essential for an efficient needle assembly. The overexpression of PscF partially compensates for the absence of the inner rod in PscI-deficient mutant by forming a secretion-proficient injectisome. All together, we propose that the polymerized PscI in P. aeruginosa optimizes the injectisome function by anchoring the needle within the envelope-embedded complex of the T3S secretome and - contrary to its counterpart in Salmonella - is not involved in substrate switching., (© 2015 John Wiley & Sons Ltd.)

Objective: To determine the rate of therapeutic management satisfying the institutional protocol for children with urinary tract infection (UTI) in the context of the emergence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae., Methods: A retrospective, single-center, observational study was carried out for 1 year (2010-2011). Data from all children admitted to the emergency department with a diagnosis of UTI were analysed. Adherence to the protocol was evaluated for the initial management and at re-evaluation with the definitive result of the urine culture. Risk factors for nonadherence were analysed., Results: Among the children, 393 were included. An ESBL Enterobacteriaceae-related UTI was identified in 2.2% of urine analyses. The initial therapeutic management satisfied the protocol for 95% of children and at re-evaluation for 80%. Nonadherence was related to poorly adapted treatment (59%) and an erroneous indication of dual antibiotic therapy (20%). Variables associated with the inadequacy of the initial management were age less than 3 months (adjusted OR [aOR]: 9.3; 95%CI: 3.5-24.8) and at re-evaluation age under 3 months (aOR: 12.8; 95%CI: 5.5-29.9) and an unconfirmed infection in the final urine culture (aOR: 30.8; 14.7-64.3)., Conclusion: Adherence to the protocol was good but could be increased by a better re-evaluation procedure with the result of the urine culture. ESBL Enterobacteriaceae-related UTIs were still rare enough to influence the efficacy of management., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Pseudomonas aeruginosa lung infections are a major cause of death in cystic fibrosis and hospitalized patients. Treating these infections is becoming difficult due to the emergence of conventional antimicrobial multiresistance. While monosaccharides have proved beneficial against such bacterial lung infection, the design of several multivalent glycosylated macromolecules has been shown to be also beneficial on biofilm dispersion. In this study, calix[4]arene-based glycoclusters functionalized with galactosides or fucosides have been synthesized. The characterization of their inhibitory properties on Pseudomonas aeruginosa aggregation, biofilm formation, adhesion on epithelial cells, and destruction of alveolar tissues were performed. The antiadhesive properties of the designed glycoclusters were demonstrated through several in vitro bioassays. An in vivo mouse model of lung infection provided an almost complete protection against Pseudomonas aeruginosa with the designed glycoclusters.

Rationale: Pseudomonas aeruginosa, a major problem pathogen responsible for severe infections in critically ill patients, triggers, through a functional type-3 secretion system (T3SS), the activation of an intracellular cytosolic sensor of innate immunity, NLRC4. Although the NLRC4-inflammasome-dependent response contributes to increased clearance of intracellular pathogens, it seems that NLRC4 inflammasome activation decreases the clearance of P. aeruginosa, a mainly extracellular pathogen., Objectives: We sought to determine the underlying mechanisms of this effect of the activation of NLRC4 by P. aeruginosa., Methods: We established acute lung injury in wild-type and Nlrc4(-/-) mice using sublethal intranasal inocula of P. aeruginosa strain CHA expressing or not a functional T3SS. We studied 96-hour survival, lung injury, bacterial clearance from the lungs, cytokine secretion in bronchoalveolar lavage, lung antimicrobial peptide expression by quantitative polymerase chain reaction, and flow cytometry analysis of lung cells., Measurements and Main Results: Nlrc4(-/-) mice showed enhanced bacterial clearance and decreased lung injury contributing to increased survival against extracellular P. aeruginosa strain expressing a functional T3SS. The mechanism involved decreased NLRC4-inflammasome-driven IL-18 secretion attenuating lung injury caused by excessive neutrophil recruitment. Additionally, in the lungs of Nlrc4(-/-) mice secretion of IL-17 by innate immune cells was increased and responsible for increased expression of lung epithelial antimicrobial peptides. Furthermore, IL-18 secretion was found to repress IL-17 and IL-17-driven lung antimicrobial peptide expression., Conclusions: We report a new role of the T3SS apparatus itself, independently of exotoxin translocation. Through NLRC4 inflammasome activation, the T3SS promotes IL-18 secretion, which dampens a beneficial IL-17-mediated antimicrobial host response.

One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection.

Pseudomonas aeruginosa and Candida albicans are two pathogens frequently encountered in the intensive care unit microbial community. We have demonstrated that C. albicans airway exposure protected against P. aeruginosa-induced lung injury. The goal of the present study was to characterize the cellular and molecular mechanisms associated with C. albicans-induced protection. Airway exposure by C. albicans led to the recruitment and activation of natural killer cells, innate lymphoid cells (ILCs), macrophages, and dendritic cells. This recruitment was associated with the secretion of interleukin-22 (IL-22), whose neutralization abolished C. albicans-induced protection. We identified, by flow cytometry, ILCs as the only cellular source of IL-22. Depletion of ILCs by anti-CD90.2 antibodies was associated with a decreased IL-22 secretion and impaired survival after P. aeruginosa challenge. Our results demonstrate that the production of IL-22, mainly by ILCs, is a major and inducible step in protection against P. aeruginosa-induced lung injury. This cytokine may represent a clinical target in Pseudomonas aeruginosa-induced lung injury.