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Background Resistance to linezolid has become a worldwide concern since it is one of the last-resort antibiotics to treat multidrug-resistant staphylococcal and enterococcal infections. Objectives We investigated staphylococcal infections caused by 16 cfr-positive linezolid-resistant Staphylococcus epidermidis and Staphylococcus aureus isolates in a French university hospital from 2015 to 2018. Methods Antimicrobial susceptibility of isolates was tested by broth microdilution and gradient strips. Genetic determinants of linezolid resistance (including cfr gene and 23S rRNA mutations) were assessed by PCR and WGS; the latter was also used to characterize the cfr-carrying plasmids in S. epidermidis and S. aureus, and to explore the clonal relationship of isolates. Results All linezolid-resistant staphylococcal isolates harboured the same cfr-carrying plasmid, sharing 99% identity with the previously described pSA737. The three S. aureus isolates belonged to different STs (ST8, ST72, ST2416); the 13 methicillin-resistant S. epidermidis (MRSE) belonged to ST2 and harboured both cfr and mutations in genes encoding 23S rRNA and ribosomal proteins. Phylogenetic analysis grouped the MRSE isolates into two clusters, one of which (n = 12 isolates) belonged to the recently reported multidrug-resistant worldwide-disseminated S. epidermidis lineages. Conclusions The results presented herein highlight the persistence and efficient spread of a cfr-carrying plasmid in a hospital related both to the dissemination of a multidrug-resistant S. epidermidis clone and the in vivo interspecies transfer of cfr between S. epidermidis and S. aureus. The emergence of linezolid-resistant strains should be closely monitored, and the mechanisms involved systematically explored in order to limit the spread of plasmid-mediated resistance.

We investigated the impact of the COVID-19 and national pandemic response on the epidemiology of Extended Spectrum Beta-Lactamase producing E. coli (ESBL-E.coli) in France.Individual microbiology records from clinical laboratories were analyzed between 1 January 2019 to 31 December 2020. The ESBL-E.coli rates from clinical samples of patients in primary care and nursing home residents were compared before and after the general lockdown in March 2020, according to demographic and geographical characteristics. Interrupted time series analyses were performed to detect measurable changes in the trend of ESBL-E.coli rates.Records covering 793,954 E. coli isolates from 1022 clinical laboratories were analyzed. In primary care, 3.1% of E. coli isolates from clinical samples were producing ESBL before March 2020 and 2.9% since May 2020 (p 0.001). The proportion of ESBL-E.coli decreased significantly among urine cultures, females, age categories 5-19, 40-64, 65 year-old, and in the North, West, East and South-East regions. In nursing home, the ESBL-E.coli rate was 9.3% (monthly rate min-max: 6.5-10.5%) before March 2020 and 8.3% (7.2-9.1%) since May 2020 (p 0.001). The reduction rate accelerated from -0.04%/month to -0.22%/month from May 2020 (p 0.001).Investigation of factors that led to the decreased proportion of ESBL-E.coli during the COVID-19 pandemic is urgently needed.

Objectives The prevalence of ESBL-producing Escherichia coli (ESBL-E. coli) in community-acquired urinary tract infections (UTI) has been increasing worldwide since 2000, but with large geographical variations. The aim of this study was to determine whether the ESBL-E. coli rate in urine samples from individuals with community-acquired UTI was associated with the local socio-economic, environmental, agricultural and healthcare characteristics. Methods This was a cross-sectional study in western France using data on antibiotic susceptibility of E. coli isolated from urine samples of individuals with community-acquired UTI analysed in non-hospital laboratories from 2015 to 2017. The ESBL-E. coli rate was calculated for each laboratory. Data on socio-economic characteristics, human antibiotic consumption, hospital bed density, animal farming density and percentage of agricultural land and surface water were retrieved at the municipality level and aggregated by study area. Their association with ESBL-E. coli prevalence was quantified using multivariate linear regression models with a backward selection. Results From 358 291 E. coli isolates from urine samples tested in 92 laboratories, the mean ESBL-E. coli prevalence for the study period was 3.30%. In an adjusted model, the ESBL-E. coli rate was significantly (P 65 years old, third-generation cephalosporin use (DDD/1000 inhabitants), number of hospital beds/km2, poultry density, pig density and percentage of agricultural land. Lower deprivation was associated with a higher ESBL-E. coli rate. Conclusions Several anthropogenic factors (primary care, hospitals and animal farming) are associated with the local ESBL-E. coli rate in community-acquired UTI. These results could contribute to improve risk management, including identification of at-risk patient groups.

Purpose The prevalence of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) has been increasing worldwide since the early 2000s. E. coli is found in 70-90% of community-acquired urinary tract infections (CA-UTIs). We performed a systematic literature review to determine the risk factors for CA-UTI caused by ESBL-EC. Methods We searched the MEDLINE, Cochrane Library, Embase and Web of Science databases without language or date restriction up to March 2019. Two independent reviewers selected studies with quantified risk factors for CA-UTI due to ESBL-EC, and assessed their quality using the Newcastle-Ottawa Scale. Results Among the 5,597 studies identified, 16 observational studies (n=12,138 patients) met the eligibility criteria. The included studies were performed in various countries, and 14/16 were published after 2012. The most relevant risk factors for CA-UTI due to ESBL-EC identified were prior use of antibiotics (odds ratio (OR) from 2.2 to 21.4), previous hospitalization (OR: 1.7 to 3.9), and UTI history (OR: 1.3 to 3.8). Two risk factors were related to environmental contamination: travelling abroad, and swimming in freshwater. Conclusion Our findings could allow adapting empiric antibiotic treatments according to the patient profile. Further studies are needed to quantify the relationships between CA-UTI due to ESBL-EC and the environment.

Diabetic wound infection is a frequent complication that may result in limb amputation. To develop new treatment strategies in response to increasing bacterial resistance, animal models are needed. We created a diabetic mouse model with chronically infected wounds. Diabetes was induced using streptozotocin, and wounds were performed using a biopsy punch, and then infected with a clinical strain of Staphylococcus aureus. Chronification was reached by delaying healing thanks to chemical products (aminotriazole and mercaptosuccinic acid). Overall survival, as well as clinical, bacteriological and immunological data in skin, blood and spleens were collected at days 1, 7, and 14 after wounding. After a transient bacteremia proved by bacteria presence in spleen and kidneys in the first days after wounding, infected mice showed a chronic infection, with a bioburden impairing the healing process, and bacteria persistence compared to control mice. Infected mice showed gradual increasing skin levels of IL-17A compared to control mice that resulted in an IL-17/IFN-γ inbalance, pointing out a localized Th17 polarization of the immune response. Whether infected or not, the skin level of IL-10 decreased dramatically at days 1 and 7 after wounding, with an increase observed only in the control mice at day 14. After a decrease at day 1 in both groups, spleen IL-10 showed a rather steady level at days 7 and 14 in the control group compared with the decrease observed in the infected group. The spleen IL-10/IFN-γ ratio showed a systemic inflammatory response with Th1 polarization. Therefore, this model provides useful data to study wound healing. It is easy to reproduce, affordable and offers clinical and biological tools to evaluate new therapeutics.

Background Antimicrobial resistance (AMR) has been widely recognized as a major public health issue, which can be addressed through effective AMR surveillance systems. In 2018, a national surveillance programme for AMR in the community and nursing homes called Mission PRIMO was established in France. It builds on an existing network called MedQual-Ville that had been monitoring AMR mainly in the west of France community since 2003. Objectives and Methods To evaluate the MedQual-Ville surveillance activities and to formulate practical recommendations for improvement, using a semi-quantitative evaluation framework called OASIS. Results The evaluation showed that MedQual-Ville is overall a well-performing surveillance system. Its major strengths rely on excellent coordination and internal communication with clinical laboratories that participate on a voluntary basis. Surveillance objectives and procedures are clear to all participants. Hence, the quality and reliability of the data being produced is very high. At this stage, the major area for improvement is representativeness, with poor coverage achieved in several densely populated areas. Besides, the utility and impact of surveillance data could be improved by strengthening communication towards end-users, especially local prescribers. Conclusions There is currently no European programme or guidance for AMR surveillance in the community and nursing homes. Our results partly fill this gap, by evaluating how surveillance is being performed in France and providing recommendations that could be applicable to other countries with similar health systems. This work also highlighted the relevance of OASIS for evaluation of surveillance systems in the human sector.

ImportanceExtended-spectrum β-lactamase (ESBL)–producing Escherichia coli is considered a leading pathogen contributing to the global burden of antimicrobial resistance.ObjectiveTo better understand factors associated with the heterogeneity of community-acquired ESBL-producing E coli urinary tract infections (UTIs) in France.Design, Setting, and ParticipantsThis cross-sectional study performed from January 1 to December 31, 2021, was based on data collected via PRIMO (Surveillance and Prevention of Antimicrobial Resistance in Primary Care and Nursing Homes), a nationwide clinical laboratory surveillance system in France. Strains of E coli isolated from community urine samples from January 1 to December 31, 2019, from 59 administrative departments of metropolitan France were included.Main Outcomes and MeasuresQuasi-Poisson regression models were used to assess the associations between several ecological factors available on government and administration websites between 2010 and 2020 (demographic population structure, living conditions, baseline health care services, antibiotic consumptions, economic indicators, animal farming density, and environmental characteristics) and the number of ESBL-producing E coli strains isolated from urine samples of individuals with community-acquired UTI in 2019.ResultsAmong 444 281 E coli isolates from urine samples tested in 1013 laboratories, the mean prevalence of ESBL-producing E coli was 3.0% (range, 1.4%-8.8%). In an adjusted model, the number of community-acquired ESBL-producing E coli UTIs in each department was positively associated with the percentage of children younger than 5 years (adjusted β1 coefficient, 0.112 [95% CI, 0.040-0.185]; P = .004), overcrowded households (adjusted β1 coefficient, 0.049 [95% CI, 0.034 to 0.062]; P 1 coefficient, 0.002 [95% CI, 0.001-0.002]; P 1 coefficient, 0.0002 [0.00004 to 0.00039]; P = .02), and poultry density (adjusted β1 coefficient, 0.0001 [95% CI, 0.0001-0.0002]; P 1 coefficient, −0.115 [95% CI, −0.165 to −0.064]; P 1 coefficient, −0.052 [−0.081 to −0.024]; P = .001) were negatively associated with a higher number of community-acquired ESBL-producing E coli UTIs.Conclusions and RelevanceThe findings of this cross-sectional study suggest that multiple human health, animal health, and environmental factors are associated with the occurence of community-acquired ESBL E coli UTI. Strategies to mitigate ESBL in the community should follow the One Health approach and address the role played by fluoroquinolones, tetracycline use, poultry density, overcrowded households, and preschool-aged children.

Objectives Oral treatment of febrile urinary tract infections (FUTIs) can be impaired by MDR Enterobacterales often combining ESBL and inhibitor-resistant genes. We studied the impact of β-lactamases and Enterobacterales’ genotypes on the cefixime, cefpodoxime and mecillinam ± amoxicillin/clavulanate MICs. Materials and methods In this multicentric study, we included 251 previously whole-genome-sequenced ESBL-producing Enterobacterales, isolated in French children with FUTIs. The MICs of cefixime, cefpodoxime, mecillinam alone and combined with amoxicillin/clavulanate were determined and analysed with respect to genomic data. We focused especially on the isolates’ ST and their type of β-lactamases. Clinical outcomes of patients who received cefixime + amoxicillin/clavulanate were also analysed. Results All isolates were cefixime and cefpodoxime resistant. Disparities depending on blaCTX-M variants were observed for cefixime. The addition of amoxicillin/clavulanate restored susceptibility for cefixime and cefpodoxime in 97.2% (MIC50/90 of 0.38/0.75 mg/L) and 55.4% (MIC50/90 of 1/2 mg/L) of isolates, respectively, whatever the ST, the blaCTX-M variants or the association with inhibitor-resistant β-lactamases (34.2%). All isolates were susceptible to mecillinam + amoxicillin/clavulanate with MIC50/90 of 0.19/0.25 mg/L, respectively. Neither therapeutic failure nor any subsequent positive control urine culture were reported for patients who received cefixime + amoxicillin/clavulanate as an oral relay therapy (n = 54). Conclusions Despite the frequent association of ESBL genes with inhibitor-resistant β-lactamases, the cefixime + amoxicillin/clavulanate MICs remain low. The in vivo efficacy of this combination was satisfying even when first-line treatment was ineffective. Considering the MIC distributions and pharmacokinetic parameters, mecillinam + amoxicillin/clavulanate should also be an alternative to consider when treating FUTIs in children.

Assessment of the quality of initial care is necessary to target priority actions that can reduce the still high morbidity and mortality due to community-onset severe bacterial infections (COSBIs) among children.To study the prevalence, characteristics, and determinants of suboptimal care in the initial management of COSBIs.This prospective, population-based, cohort study and confidential enquiry was conducted between August 2009 and January 2014 in western France, a region accounting for 15% of the French pediatric population (1 968 474 children aged 1 month to 16 years) and including 6 pediatric intensive care units (PICUs) and 35 emergency departments. Participants included all children aged 1 month to 16 years who died before PICU admission or were admitted to a PICU with a COSBI (ie, bacterial sepsis, including meningitis, purpura fulminans, and pulmonary, osteoarticular, intra-abdominal, cardiac, and soft-tissue severe infections). Data were analyzed from March to June 2020.Suboptimal care determined according to evaluation of 8 types of care: (1) the delay in seeking care by family, (2) the physician's evaluation of severity, (3) the patient's referral at the first consultation with signs of severity, (4) the timing and (5) dosage of antibiotic treatment, (6) the timing and (7) volume of fluid bolus administration, and (8) the clinical reassessment after fluid bolus.Two experts assessed the quality of care before death or PICU admission as optimal, possibly suboptimal, or certainly suboptimal. The consequences and determinants of certainly suboptimal care were identified with multinomial logistic regression and generalized linear mixed models.Of the 259 children included (median [IQR] age, 24 [6-66] months; 143 boys [55.2%]), 27 (10.4%) died, and 25 (9.6%) had severe sequelae at PICU discharge. The quality of care was certainly suboptimal in 89 cases (34.4%). Suboptimal care was more frequent in children with sequelae (adjusted odds ratio [aOR], 5.61; 95% CI, 1.19-26.36) and less frequent in children who died (aOR, 0.16; 95% CI, 0.04-0.65) vs those surviving without sequelae. Factors independently associated with suboptimal care were age younger than 5 years (aOR, 3.15; 95% CI, 1.25-7.90), diagnosis of sepsis with no source (aOR, 5.77; 95% CI, 1.64-20.30) or meningitis (aOR, 3.39; 95% CI, 1.15-9.96) vs other severe infections, and care by a primary care physician (aOR, 3.22; 95% CI, 1.17-8.88) vs a pediatric hospital service.This study found that suboptimal care is frequent in the initial management of COSBI and is associated with severe sequelae. The paradoxical association with reduced risk of death may be explained by an insufficient adjustment on bacterial or host intrinsic factors. Management could be optimized by improving the quality of primary care, especially for young children.

The management of diabetic foot infections is frequently a dead end for surgeons and infectious disease specialists. When the pathogen to be treated is not resistant to conventional antibiotics, the latter tend to unbalance the intestinal microbiota, which is linked to multiple pathologies. A local treatment with bacteriophages, in addition to being as much or even more effective than antibiotics from a clinical and microbiological point of view, makes it possible to respect the patient’s microbiota. These results suggest that the use of this therapeutic alternative is a major avenue and that the introduction of recommendations for their use is now necessary., Diabetes is marked by a range of complications, including chronic infections that can lead to limb amputation. The treatment of infected wounds is disrupted by arteriopathies that reduce tissue perfusion as well as by the critical development of bacterial resistance. We evaluated the impact of a local application of bacteriophages compared to that of a per os administration of amoxicillin-clavulanic acid in a mouse model of Staphylococcus aureus wound infection. We found that phage treatment resulted in improved clinical healing and a reduction in local bacterial load at 7 and 14 days postinfection. Unlike antibiotics, phage therapy did not deplete the intestinal microbiota of treated animals. Amoxicillin resulted in a reduction of alpha and beta diversities of the murine microbiota and disturbed architecture even 7 days after the end of treatment, whereas phage treatment did not impinge on the microbiota. IMPORTANCE The management of diabetic foot infections is frequently a dead end for surgeons and infectious disease specialists. When the pathogen to be treated is not resistant to conventional antibiotics, the latter tend to unbalance the intestinal microbiota, which is linked to multiple pathologies. A local treatment with bacteriophages, in addition to being as much or even more effective than antibiotics from a clinical and microbiological point of view, makes it possible to respect the patient’s microbiota. These results suggest that the use of this therapeutic alternative is a major avenue and that the introduction of recommendations for their use is now necessary.

International audience; Objectives: We aimed to evaluate the probability to achieve PK-PD targets in patients with sepsis hospitalized in the intensive care unit (ICU) after a single dose of 30mg/kg of amikacin or 8mg/kg of gentamicin.Patients and methods: This single-center prospective study included 138 ICU patients with severe sepsis or septic shock with an indication for intravenous amikacin (N=89) or gentamicin (N=49). Maximum concentration (Cmax) was measured 30 minutes after infusion completion. PK/PD objectives were respectively Cmax≥60mg/L and ≥30mg/L for amikacin and gentamicin for empirical therapy, and a Cmax/MIC ratio≥8, as per French guidelines.Results: The median Simplified Acute Physiology Score II was 43 and ICU case fatality rate was 34.8%. A causative bacterial agent was identified in 94 patients (68.1%). Three pathogens had acquired aminoglycoside resistance and 15 were naturally resistant. The targeted Cmax for the first dose was achieved in 53 patients (59.6%) receiving amikacin, and one (2.2%) patient receiving gentamicin. Cmax/MIC ratio≥8 was obtained in all patients infected with susceptible pathogens (N=72). Factors associated with Cmax≥60mg/L of amikacin in multivariate analysis were dose per kg of adapted body weight (OR=1.39, P

International audience; Natural killer (NK) cells play a key role in both antibacterial and antitumor immunity. Pseudomonas aeruginosa infection has already been reported to alter NK cell functions. We studied in vitro the effect of P. aeruginosa on NK cell cytotoxic response (CD107a membrane expression) to a lymphoma cell line. Through positive and negative cell sorting and adoptive transfer, we determined the influence of monocytes, lymphocytes, and regulatory T cells (Treg) on NK cell function during P. aeruginosa infection. We also studied the role of the activating receptor natural killer group 2D (NKG2D) in NK cell response to B221. We determined that P. aeruginosa significantly altered both cytotoxic response to B221 and NKG2D expression on NK cells in a Treg-dependent manner and that the NKG2D receptor was involved in NK cell cytotoxic response to B221. Our results also suggested that during P. aeruginosa infection, monocytes participated in Treg-mediated NK cell alteration. In conclusion, P. aeruginosa infection impairs NK cell cytotoxicity and alters antitumor immunity. These results highlight the strong interaction between bacterial infection and immunity against cancer.

Sepsis causes inflammation-induced immunosuppression with lymphopenia and alterations of CD4+ T-cell functions that renders the host prone to secondary infections. Whether and how regulatory T cells (Treg) are involved in this postseptic immunosuppression is unknown. We observed in vivo that early activation of Treg during Staphylococcus aureus sepsis induces CD4+ T-cell impairment and increases susceptibility to secondary pneumonia. The tumor necrosis factor receptor 2 positive (TNFR2pos) Treg subset endorsed the majority of effector immunosuppressive functions, and TNRF2 was particularly associated with activation of genes involved in cell cycle and replication in Treg, probably explaining their maintenance. Blocking or deleting TNFR2 during sepsis decreased the susceptibility to secondary infection. In humans, our data paralleled those in mice; the expression of CTLA-4 was dramatically increased in TNFR2pos Treg after culture in vitro with S. aureus. Our findings describe in vivo mechanisms underlying sepsis-induced immunosuppression and identify TNFR2pos Treg as targets for therapeutic intervention.

Current guidelines recommend cefazolin as an alternative to antistaphylococcal penicillins (ASPs) in methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis despite the lack of comparative study. The objective of this study was to evaluate the comparative outcomes of cefazolin vs. ASPs in MSSA infective endocarditis.This was a retrospective analysis of an observational multicentre cohort study using prospectively collected data from patients with MSSA endocarditis confirmed by endocarditis team and treated either with cefazolin or ASPs between July 2013 and December 2018. Patients were excluded if they received both treatments. The primary outcome was 90-day all-cause mortality.Of 210 patients included, 53 patients (25.2%) received cefazolin and 157 (74.8%) received ASPs. The overall 90-day mortality rate was 27.6% (58/210 patients), 24.5% (13/53) in the cefazolin group vs. 28.7% (45/157) in the ASP group (p 0.561). Premature antimicrobial discontinuation due to adverse events occurred less frequently with cefazolin than with ASPs (0/53 vs. 13/157 patients; p 0.042). In multivariate analysis, there was no difference in 90-day mortality between cefazolin and ASPs (adjusted odds ratio (aOR), 1.2; 95% confidence interval (CI), 0.49-2.91; p 0.681), while age (aOR, 1.06; 95% CI, 1.03-1.09; p 0.001), Charlson comorbidity index (aOR, 1.18; 95% CI, 1.02-1.36 p 0.023), cerebral embolism (aOR, 2.83; 95% CI, 1.33-6.14; p 0.007) and intensive care unit admission (aOR, 4.16; 95% CI, 1.89-9.59; p 0.001) were factors significantly associated with higher mortality.Cefazolin seems to be a possible alternative to ASPs in MSSA endocarditis. More studies are needed to confirm these results and determine which treatment should be recommended as first-line therapy.

Objectives To characterize and compare resistance trends in clinical Escherichia coli isolates from humans, food-producing animals (poultry, cattle and swine) and pets (dogs and cats). Methods Antibiogram results collected between January 2014 and December 2017 by MedQual [the French surveillance network for antimicrobial resistance (AMR) in bacteria isolated from the community] and RESAPATH (the French surveillance network for AMR in bacteria from diseased animals) were analysed, focusing on resistance to antibiotics of common interest to human and veterinary medicine. Resistance dynamics were investigated using generalized additive models. Results In total, 743 637 antibiograms from humans, 48 170 from food-producing animals and 7750 from pets were analysed. For each antibiotic investigated, the resistance proportions of isolates collected from humans were of the same order of magnitude as those from food-producing animals or pets. However, resistance trends in humans differed from those observed in pets and food-producing animals over the period studied. For example, resistance to third-generation cephalosporins and fluoroquinolones was almost always below 10% for both humans and animals. However, in contrast to the notable decreases in resistance observed in both food-producing animals and pets, resistance in humans decreased only slightly. Conclusions Despite several potential biases in the data, the resistance trends remain meaningful. The strength of the parallel is based on similar data collection in humans and animals and on a similar statistical methodology. Resistance dynamics seemed specific to each species, reflecting different antibiotic-use practices. These results advocate applying the efforts already being made to reduce antibiotic use to all sectors and all species, both in human and veterinary medicine.

Objectives To describe the epidemiology of community-onset severe bacterial infections in children and its recent evolution. Design Prospective, observational, population-based study from 2009 to 2014. Setting An administrative area accounting for 13% of the French pediatric population. Patients All children 1 month to 16 years old who died before admission or were admitted to a PICU for a community-onset severe bacterial infection. Interventions None. Measurements and main results The incidence and mortality rate of community-onset severe bacterial infections were compared with data from a reference population-based study conducted between 2000 and 2006, that is, before national recommendations for antimeningococcal C and antipneumococcal generalized vaccinations. Among the 261 children included (median age 25 mo), 28 (10.7%) died. The main diagnoses were meningitis (n = 85; 32%) and purpura fulminans (n = 59; 22%). The most common isolated bacteria were Neisseria meningitidis (n = 75; 29%), including 47 (63%) cases of serogroup B and 15 (20%) serogroup C, Streptococcus pneumoniae (n = 49, 19%), and Staphylococcus aureus (n = 15; 6%). The incidence of community-onset severe bacterial infections was three per 100,000 person-years (95% CI, 2.6-3.3) and had decreased by 53% from the reference period. Mortality rate was 0.3 per 100,000 person-years (95% CI, 0.2-0.4) and had decreased by 73% from the reference period. The incidence of community-onset severe bacterial infections caused by N. meningitidis and S. pneumoniae was 0.8 and 0.5 per 100,000 person-years and had decreased by 70% and 67% from the reference period. The incidence of community-onset severe bacterial infections-related to Staphylococcus aureus was 0.16 per 100,000 person-years and had increased by 220% from the reference period. Conclusions The incidence and mortality rate of community-onset severe bacterial infections, except for S. aureus infection, have decreased in France. N. meningitidis and S. pneumoniae continue to account for many infections, which indicates the need for better vaccination coverage and spectrum.

Background Almost 15% of patients with ulcerative colitis (UC) will require a proctocolectomy with ileal pouch–anal anastomosis (IPAA) as a result of fulminant colitis, dysplasia, cancer, or medical refractory diseases. Around 50% will experience pouchitis, an idiopathic inflammatory condition involving the ileal reservoir, responsible for digestive symptoms, deterioration in quality of life, and disability. Though the majority of initial cases of pouchitis are easily managed with a short course of antibiotics, in about 10% of cases, inflammation of the pouch becomes chronic with very few treatments available. Previous studies have suggested that manipulating the composition of intestinal flora through antibiotics, probiotics, and prebiotics achieved significant results for treating acute episodes of UC-associated pouchitis. However, there is currently no established effective treatment for chronic antibiotic-dependent pouchitis. Fecal microbiota transplantation (FMT) is a novel therapy involving the transfer of normal intestinal flora from a healthy donor to a patient with a medical condition potentially caused by the disrupted homeostasis of intestinal microbiota or dysbiosis. Methods Our project aims to compare the delay of relapse of chronic recurrent pouchitis after FMT versus sham transplantation. Forty-two patients with active recurrent pouchitis after having undergone an IPAA for UC will be enrolled at 12 French centers. The patients who respond to antibiotherapy will be randomized at a ratio of 1:1 to receive either FMT or sham transplantation. Discussion On April 30, 2014, the World Health Organization published an alarming report on antibiotic resistance. Finding an alternative medical treatment to antibiotics in order to prevent relapses of pouchitis is therefore becoming increasingly important given the risk posed by multiresistant bacteria. Moreover, if the results of this study are conclusive, FMT, which is less expensive than biologics, could become a routine treatment in the future. Trial registration ClinicalTrials.gov, NCT03524352. Registered on 14 May 2018.

BACKGROUND: There is currently a lack of evidence for the relative effectiveness of partial resection (PR) and total resection (TR) before managing abdominal aortic graft infection (AGI). Most authorities agree that TR is mandatory for intracavitary AGI in patients with favorable conditions but there is an increasing number of patients with severe comorbidities for whom this approach is not suitable, resulting in a prohibitive mortality rate. The purpose of this study was to determine the most appropriate indication for TR or PR. METHODS: A meta-analysis was conducted on the rates of early/late mortality, amputations and reinfection. A meta-regression was performed with 8 variables: patient age, male prevalence, presence of virulent or nonvirulent organisms, urgency, omentoplasty and follow-up. RESULTS: Twenty-one studies and 1.052 patients were included. For TR and PR the rates of early mortality and reinfection were 16.8% and 10.5%, 11% and 27% respectively. For TR urgency and male gender were associated with increased rate of early mortality and male gender, PDF and virulent organisms were associated with increased risk of reinfection. For PR no statistical correlation was analyzable except for PDF with increased risk of reinfection. CONCLUSIONS: Early mortality rates are higher for TR and reinfection rates are higher for PR. For TR early mortality increases in urgent cases and it is suggested that alternative option must be discussed, reinfection decreases in the presence of nonvirulent organisms and TR seems optimal. For TR and PR reinfection increases in presence of PDF and alternative technique may be more appropriate.

Background Interleukin (IL)-22 is a cytokine involved in tissue protection and repair following lung pathologies. Interferon (IFN)-λ cytokines displayed similar properties during viral infection and a synergy of action between these two players has been documented in the intestine. We hypothesize that during Pseudomonas aeruginosa challenge, IL-22 up-regulates IFN-λ and that IFN-λ exhibits protective functions during Pseudomonas aeruginosa acute pneumonia model in mice. Methods Using an in vitro human alveolar epithelial cell line A549, we assessed the ability of IL-22 to enhance IFN-λ expression during infection. IFN-λ protective function was evaluated in an acute mouse pneumonia model. Results We first demonstrated in murine lungs that only type-II alveolar cells express IL-22 receptor and that IL-22 treatment of A549 cell line up-regulates IFN-λ expression. In a murine acute pneumonia model, IL-22 administration maintained significant IFN-λ levels in the broncho-alveolar fluids whereas IL-22 neutralization abolished IFN-λ up-regulation. In vivo administration of IFN-λ during Pseudomonas aeruginosa pneumonia improves mice outcome by dampening neutrophil recruitment and decreasing epithelium damages. Discussion We show here that IL-22 regulates IFN-λ levels during Pseudomonas aeruginosa pneumonia.

Biofilms produced by Pseudomonas aeruginosa present a serious threat to cystic fibrosis patients. Here, we report the draft genome sequences of four cystic fibrosis isolates displaying various mucoid and biofilm phenotypes. The estimated average genome size was about 6,255,986 ± 50,202 bp with a mean G+C content of 66.52 ± 0.06%.

Background In a context of suboptimal vaccination coverage and increasing vaccine hesitancy, we aimed to study morbidity and mortality in children related to missing or incomplete meningococcal C and pneumococcal conjugate vaccines. Methods We conducted a prospective, observational, population-based study from 2009 to 2014 in a French administrative area that included all children from age 1 month to 16 years who died before admission or were admitted to an intensive care unit for a community-onset bacterial infection. Vaccine-preventable infection was defined as an infection with an identified serotype included in the national vaccine schedule at the time of infection and occurring in a non- or incompletely vaccinated child. Death and severe sequelae were studied at hospital discharge. Frequencies of vaccine-preventable morbidity and mortality caused by meningococcus and pneumococcus were calculated. Results Among the 124 children with serotyped meningococcal (n = 75) or pneumococcal (n = 49) severe infections included (median age 26 months), 20 (16%) died and 12 (10%) had severe sequelae. Vaccine-preventable infections accounted for 18/124 infections (15%, 95% CI 9, 22), 5/20 deaths (25%, 95% CI 9, 49), and 3/12 severe sequelae cases (25%, 95% CI 0, 54). The vaccine schedule for meningococcal C and pneumococcal conjugate vaccinations was incomplete for 71/116 (61%) children targeted by at least one of these two vaccination programs. Conclusions Mortality and morbidity rates related to vaccine-preventable meningococcal or pneumococcal infection could be reduced by one quarter with better implementation of immunisation programs. Such information could help enhance the perception of vaccine benefits and fight vaccine hesitancy.

International audience; Objectives: Achromobacter spp. are emerging pathogens in respiratory samples from cystic fibrosis patients. The current reference methods (nrdA-sequencing or multilocus sequence typing) can identify 18 species which are often misidentified by conventional techniques as A. xylosoxidans. A few studies have suggested that matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF/MS) provides accurate identification of the genus but not of species. The aims of this study were (a) to generate a database for MALDI-TOF/MS Bruker including the 18 species, (b) to evaluate the suitability of the database for routine laboratory identification, and (c) to compare its performance with that of the currently available Bruker default database.Methods: A total of 205 isolates belonging to the 18 species identified by nrdA sequencing were used to build a local database. Main spectra profiles (MSPs) were created according to Bruker's recommendations for each isolate with the Biotyper software. Performance of the default Bruker database and ours for routine use were compared by testing 167 strains (including 38 isolates used from MSP creation) belonging to the 18 species identified by nrdA sequencing directly from colonies cultivated on various media.Results: Our new database accurately identified 99.4% (166/167) of the isolates from the 18 species (score ≥2.0) versus only 50.9% (85/167) with the Bruker database. In the Bruker database 17.3% of the isolates (29/167) were incorrectly identified as another species despite a score of ≥2.0.Conclusions: The use of MALDI-TOF/MS in combination with a database developed with samples from 18 Achromobacter species provides rapid and accurate identification. This tool could be used to help future clinical studies.

Impeding, as well as reducing, the burden of antimicrobial resistance in Gram-negative pathogens is an urgent public health endeavor. Our current antibiotic armamentarium is dwindling, while major resistance determinants (e.g., extended-spectrum β-lactamases [ESBLs]) continue to evolve and disseminate around the world. One approach to attack this problem is to develop novel therapies that will protect our current agents. AAI101 is a novel penicillanic acid sulfone β-lactamase inhibitor similar in structure to tazobactam, with one important difference. AAI101 possesses a strategically placed methyl group that gives the inhibitor a net neutral charge, enhancing bacterial cell penetration. AAI101 paired with cefepime, also a zwitterion, is in phase III of clinical development for the treatment of serious Gram-negative infections. Here, AAI101 was found to restore the activity of cefepime against class A ESBLs (e.g., CTX-M-15) and demonstrated increased potency compared to that of piperacillin-tazobactam when tested against an established isogenic panel. The enzymological properties of AAI101 further revealed that AAI101 possessed a unique mechanism of β-lactamase inhibition compared to that of tazobactam. Additionally, upon reaction with AAI101, CTX-M-15 was modified to an inactive state. Notably, the in vivo efficacy of cefepime-AAI101 was demonstrated using a mouse septicemia model, indicating the ability of AAI101 to bolster significantly the therapeutic efficacy of cefepime in vivo. The combination of AAI101 with cefepime represents a potential carbapenem-sparing treatment regimen for infections suspected to be caused by Enterobacteriaceae expressing ESBLs.

International audience; We previously reported the distribution of Achromobacter spp. (species and Sequence Types (ST)) in our French Cystic Fibrosis (CF) centre. In the present study we collected 109 Achromobacter isolates (1/patient) from 9 other French CF Centres for species identification, antimicrobial susceptibility testings and Multilocus-Sequence-Typing (MLST) analysis. Ten species were detected, A. xylosoxidans being the most predominant one (73.4% of the isolates). Piperacillin-tazobactam, ceftazidime, imipenem, meropenem and ciprofioxacin were respectively active against 88, 70, 79, 72 and 23% of the isolates. Among the 79 A. xylosoxidans isolates, 46 STs were detected. Interestingly, ST 137, recovered in 4 centres (5 patients), was previously detected in our centre (2 patients). The strains from the 7 patients belonged to the same pulsotype (pulsed-field-gel-electrophoresis analysis) and harboured acquired resistance to meropenem, ceftazidime, ciprofioxacin, and except for 2 isolates, to imipenem and piperacillin-tazobactam. This is the first description in France of a circulating multiresistant A. xylosoxidans strain.

The authors regret there were mistakes in Table 12 concerning adjusted risk estimation for surgical site infections of the lower limbs. The authors would like to thank Dr Tresson and colleagues for their careful reading and to apologise for any inconvenience. Table 12 should be read as below

International audience; A polyphasic taxonomic study was performed on two Gram-positive-staining, anaerobic, pleomorphic, rod-shaped strains isolated from human bone and tissue samples. Sequencing of the 16S rRNA genes revealed that the strains belong to a novel species within the genus Propionibacterium, most closely related to Propionibacterium acnes subsp. acnes and Propionibacterium acnes subsp. elongatum with similarity values of 98.4 % and 98.1 %, respectively. In addition, protein-coding genes for rpoB, recA and gyrB clearly separated the novel organism from all species and subspecies of the genus Propionibacterium. However, a DNA–DNA hybridization analysis between the novel organism and the type strain P. acnes ATCC 6919[T] revealed a value of only 61.1 %. Furthermore, whole genome analysis using the program OrthoANI gave a value of 88.5 %, which is significantly below the cutoff value of 95 % for species delineation. The major fatty acids were iso-C 15 : 0 , anteiso-C 15 : 0 and iso-C 17 : 0. The DNA G+C content of the type strain was 59.7 mol%. When taken collectively, phenotypic, molecular genetic, chemotaxonomic and phylogenetic information demonstrate that the organism represents a distinct, albeit close relative of P. acnes On the basis of the results presented, the organism represents a novel member of the genus Propionibacterium for which the name Propionibacterium namnetense sp. nov. is proposed. The type strain is NTS 31307302[T] (=DSM 29427[T] =CCUG 66358[T]).

Staphylococcus aureus bone and joint infection (BJI) is associated with significant rates of chronicity and relapse. In this study, we investigated how S. aureus is able to adapt to the human environment by comparing isolates from single patients with persisting or relapsing BJIs that were recovered during the initial and recurrent BJI episodes. In vitro and in vivo assays and whole-genome sequencing analyses revealed that the recurrent isolates induced a reduced inflammatory response, formed more biofilms, persisted longer in the intracellular compartments of host bone cells, were less cytotoxic and induced less mortality in a mouse infection model compared with the initial isolates despite the lack of significant changes at the genomic level. These findings suggest that S. aureus BJI chronicization is associated with an in vivo bacterial phenotypical adaptation that leads to decreased virulence and host immune escape, which is linked to increased intraosteoblastic persistence and biofilm formation.

Les infections de prothese vasculaire necessitent une prise en charge medicochirurgicale. Une antibiotherapie probabiliste pourra etre instauree avant le traitement chirurgical en cas de sepsis severe, de choc septique ou de menace de complications mecaniques septiques (desunion anastomotique, rupture anevrismale). Elle repose sur une association d’un glycopeptide, d’une betalactamine a large spectre et d’un aminoside. Une fois la ou les bacterie(s) causale(s) identifiee(s) par les hemocultures et/ou les prelevements peroperatoires et les donnees d’antibiogramme connues, une antibiotherapie specifique a spectre le plus etroit possible sera prescrite pour une duree totale de six semaines postoperatoires. En cas de traitement chirurgical non optimal, une antibiotherapie suppressive sera instauree dans les suites du traitement antibiotique usuel. La gestion chirurgicale de ces patients presentant une telle infection est complexe. Elle depend du mode de contamination de la prothese, du germe incrimine, de la localisation de la prothese infectee et de l’etat general du patient.

RESUME L’infection neonatale precoce (INP) reste une preoccupation majeure dans les pays en voie de developpement comme dans les pays industrialises. Parce qu’aucun element clinique ni marqueur biologique n’est assez sensible, ni specifique pour permettre a lui seul d’etablir le diagnostic, la prise en charge repose sur un faisceau d’arguments cliniques et biologiques et expose de nombreux nouveau-nes a des examens complementaires et antibiotherapies neonatales dont les effets deleteres sont aujourd’hui etablis (emergence de bacteries multi resistantes, perturbations du microbiote impliquees dans la survenues de pathologies ulterieures). Alors que la prevalence des infections neonatales precoces a diminue depuis la generalisation de l’antibioprophylaxie per-natale, l’evidence s’impose d’adapter notre strategie medicale a ces modifications epidemiologiques recentes. Une approche basee sur un fort niveau de preuve scientifique, combinant des donnees d’anamnese, cliniques et de biologie comme la procalcitonine semble a ce jour la meilleure strategie pour distinguer la population des nouveau-nes a tres faible risque infectieux de celle a fort risque et limiter ainsi les indications d’antibiotherapie neonatale.

Objectives To assess the meningeal penetration of cefazolin and cloxacillin in individuals treated for methicillin-susceptible staphylococcal meningitis. Methods We retrospectively identified individuals treated for Staphylococcus meningitis with measurements of cefazolin or cloxacillin concentrations in cerebrospinal fluid (CSF) using a validated assay of liquid chromatography coupled with mass spectrometry at the Nantes University Hospital between January 2009 and October 2019. Staphylococcus meningitis was defined by a compatible clinical presentation and a microbiological confirmation (positive CSF culture or positive specific PCR). Medical charts were retrospectively reviewed to collect microbiological and clinical data, and to assess therapeutic success. Results Among the 17 included individuals, eight (47%) were treated with cefazolin and nine (53%) with cloxacillin. Median daily dosages of cefazolin and cloxacillin were 8 g (range 6–12 g) and 12 g (range 10–13 g), respectively. Cefazolin and cloxacillin were mainly administered by continuous infusion. Eleven individuals (65%) were men, median (interquartile range (IQR)) age was 54 years (50; 70), 14 (82%) had postoperative meningitis and 3 (18%) had haematogenous meningitis. Median (IQR) antibiotic CSF concentrations were 2.8 mg/L (2.1; 5.2) and 0.66 mg/L (0.5; 0.9) for cefazolin and cloxacillin groups, respectively. Cloxacillin was discontinued in two individuals for therapeutic failure. Conclusions Patients with staphylococcal meningitis treated with high-dose continuous intravenous infusion of cefazolin achieved therapeutic concentrations in CSF. Cefazolin appears to be a therapeutic candidate that should be properly evaluated in this indication.

Introduction La resistance aux antibiotiques chez les souches de E. coli en soins de ville et dans les Ehpad est suivie depuis 2012. Cette surveillance decrit les caracteristiques ainsi que les tendances temporelles et geographiques des Escherichia coli multiresistants. Materiels et methodes Du 1er janvier 2012 au 31 decembre 2018, les antibiogrammes d’E. coli isoles d’echantillons d’urines ont ete collectes dans un large reseau de laboratoires. Les donnees administratives et microbiologiques ont ete telechargees par les laboratoires sur une e-plateforme dediee a la surveillance (e-outil MedQual-Ville). Les souches isolees de patients vivant a domicile ou de residents d’Ehpad ont ete incluses dans l’analyse. Les souches de patients hospitalises et les echantillons de depistage ont ete exclus. Le taux d’E. coli multiresistants etait represente par le nombre de souches resistantes aux cephalosporines de 3e generation et/ou les souches d’E. coli productrices de betalactamases a spectre etendu (BLSE) divise par le nombre total de souches. Des analyses statistiques ont ete effectuees en utilisant le test de Student. Resultats Le nombre total d’antibiogrammes inclus realises sur des souches d’E. coli variait entre 94 164 en 2012 (147 laboratoires) et 381 141 en 2018 (742 laboratoires repartis sur 11 regions). Quand un hebergement etait notifie, 95,3 % (n = 32 710) des patients residaient a domicile et 4,7 % (n = 1598) etaient residents d’Ehpad en 2012 versus 96,1 % (n = 335 338) et 3,9 % (n = 13 720) respectivement en 2018. Parmi les patients vivant a domicile, la proportion d’E. coli resistants aux C3G etait de 3,0 % en 2012, 4,2 % en 2015 et 3,2 % en 2018 (p Conclusion Cette surveillance met en evidence depuis plusieurs annees une diminution de la multiresistance concernant E. coli, que ce soit en soins de ville ou dans les Ehpad. La mise a disposition de ces indicateurs de surveillance permettra de mieux sensibiliser l’ensemble des acteurs sur l’antibioresistance au niveau regional ainsi qu’au niveau national.

Introduction Les soins en ville ont significativement change au fil du temps, du notamment a la diminution des sejours en milieu hospitalier entrainant une evolution de l’epidemiologie des infections bacteriennes. La resistance aux antibiotiques de Staphylococcus aureus (S. aureus) est surveillee dans les hopitaux alors qu’elle l’est peu dans la communaute. L’objectif de cette surveillance est d’evaluer la proportion de souches de S. aureus resistantes a la meticilline (SARM) isolees dans les hemocultures en soins de ville et de decrire les differents profils de resistances de ces souches de S. aureus. Materiels et methodes Du 1er janvier 2015 au 31 decembre 2018, les antibiogrammes de S. aureus isoles d’hemocultures ont ete collectes dans un vaste reseau de laboratoires. Les donnees administratives et microbiologiques ont ete telechargees par les laboratoires sur une e-plateforme dediee a la surveillance (e-outil MedQual-Ville). Les souches isolees de patients vivant a domicile ou residents d’etablissements d’hebergement pour personnes âgees dependantes (EHPAD) ont ete incluses dans l’etude. Les patients hospitalises ou les echantillons de depistage ont ete exclus. Le taux de resistance aux antibiotiques de S. aureus etait le nombre de souches de S. aureus resistantes divise par le nombre total de souches. Des analyses statistiques ont ete effectuees en utilisant le test de Student. Resultats Le nombre total de 504 antibiogrammes de S. aureus ont ete inclus, variant de 90 en 2015 (147 laboratoires) a 171 en 2018 (742 laboratoires couvrant 11 regions). La proportion de SARM etait de 11 % (n = 90) en 2015, 16 % (n = 86) en 2016, 11 % (n = 157) en 2017 et 10 % (n = 171) en 2018 (p non significatif). Les souches de SARM ont ete isolees de patients vivant a domicile dans 88 % des cas chaque annee (p non significatif). Parmi les souches de S. aureus sensibles a la meticilline (SASM), 4 % etaient resistantes aux fluoroquinolones en 2015, 3 % en 2016, 2 % en 2017 et 3 % en 2018 (p non significatif). La proportion de SASM resistants a l’erythromycine variait de 12 % en 2015 a 18 % en 2018. Parmi les SARM isoles, 90 % etaient resistants aux fluoroquinolones en 2015, 100 % en 2016, 83 % en 2017 et 65 % en 2018 (p non significatif). La proportion de SARM resistants a l’erythromycine variait de 30 % en 2015 a 11 % en 2018 (p non significatif). Conclusion La bacteriemie a S. aureus est une cause importante de morbi-mortalite. Les traitements non optimaux sont associes a de mauvais resultats pour les patients. Dans le but d’optimiser les traitements, les profils de resistance des souches de S. aureus circulant dans la communaute doivent etre etudies. Cette etude suggere que les souches SARM isolees d’hemocultures etaient plus sensibles aux fluoroquinolones et a l’erythromycine au fil du temps.

Introduction Les infections urinaires sont des problemes frequents chez les patients residant en Ehpad et representent une part importante de consultations des medecins. Il existe peu de donnees sur la surveillance des resistances concernant ces patients. La mission nationale PRIMO a suivi en 2018 la resistance aux antibiotiques des enterobacteries (enterobacterales) dans les Ehpad. Cette surveillance est basee sur l’e-outil MedQual-Ville, permettant une collecte prospective des profils d’antibiotiques issus des souches isolees au sein du reseau des laboratoires de biologie medicale. Materiels et methodes Toutes les souches d’enterobacterales urinaires isolees dans ces laboratoires, de janvier 2018 a decembre 2018, ont ete incluses dans l’etude. Tous les patients d’hopitaux prives et venant du service des urgences ont ete exclus. La distribution des especes bacteriennes et l’etude de l’antibioresistance pour les antibiotiques suivants : fosfomycine (FOS), nitrofurantoine (NF), cotrimoxazole (SXT), mecillinam (MEC) et les cephalosporines de 3e generation (C3G) ont ete realisees. Un test exact du Chi2 et un test de Fischer ont ete realises. Resultats En 2018, 15 896 antibiogrammes effectues sur des souches d’enterobacterales urinaires isoles de residents d’Ehpad ont ete fournis par les 742 laboratoires de biologie medicale couvrant 11 regions francaises. Escherichia coli representait la majorite des especes bacteriennes (86,3 %, n = 13 720), suivi par Klebsiella pneumoniae (9,2 %, n = 1459) et 1,9 % d’Enterobacter cloacae complex (n = 304). Les autres enterobacterales isolees comptent pour 2,6 %. Moins de 2,0 % de souches d’E. coli etaient resistantes au NF (1,0 %) et a la FOS (1,8 %). 10,6 % d’E. coli etaient resistantes au MEC, 22,6 % au SXT et 8,6 % aux C3G. Les souches de Klebsiella pneumoniae etaient significativement plus resistantes aux antibiotiques par comparaison avec les souches d’E. coli (23,6 % pour NF, 19,1 % pour FOS, 41,3 % pour MEC, 19,8 % pour SXT et 21,2 % pour les C3G ; p Conclusion La proportion de souches urinaires resistantes aux C3G isolees de patients residant en Ehpad etait plus elevee que celle des souches urinaires isolees de patients vivant a domicile.

International audience; Objectives: To evaluate the significant role played by biofilms during prosthetic vascular material infections (PVMIs).Methods: We developed an in vivo mouse model of Staphylococcus aureus PVMI allowing its direct observation by confocal microscopy to describe: (i) the structure of biofilms developed on Dacron® vascular material; (ii) the localization and effect of antibiotics on these biostructures; and (iii) the interaction between bacteria and host tissues and cells during PVMI.Results: In this model we demonstrated that the biofilm structures are correlated to the activity of antibiotics. Furthermore, live S. aureus bacteria were visualized inside the macrophages present at the biofilm sites, which is significant as antibiotics do not penetrate these immune cells.Conclusions: This intracellular situation may explain the limited effect of antibiotics and also why PVMIs can relapse after antibiotic therapy.

Diagnostic of early neonatal infection remains a serious challenge. Since clinical symptoms and biological markers are neither sensitive nor specific, a lot of newborns suspected of infection, undergo biological analysis and empirical antibiotic treatment awaiting bacteriological results. However the prevalence of the disease has dramatically decreased since the last twenty years, subsequently to the generalization of the per partum antibioprophylaxis strategy. Because the possible deleterious effects of neonatal antibiotic treatment are well described now, it appears very urgent to restrict their use to the infected newborns only. Recent studies underline the benefit of using procalcitonin (PCT) to diferentiate virai infections of bacterial infections. PCT in blood cord could become a new and efficient marker to help neonatologists taking care of infection-suspected newborns. An evidence based approach is necessary, combining anamnestic, clinical and biological data as PCT to identify the very low risk newborns population and to limit the neonatal antibiotic prescriptions.

Objective: To confirm the advantage of in situ reconstruction (ISR) over extra-anatomic reconstruction (EAR) for aortic graft infection and determine the most appropriate conduit including autogenous veins, cryopreserved allografts, and synthetic prosthesis (standard, rifampicin of silver polyesters). Methods: A meta-analysis was conducted with rate of mortality, graft occlusion, amputation, and reinfection. A meta-regression was performed with 4 factors: patients’ age, presence of prosthetic-duodenal fistula (PDF), virulent organisms, or nonvirulent organisms. Results: In situ reconstruction over EAR seems to favor all events. For the 5 conduits used for ISR, according to operative mortality, age of the patients looks to have a positive correlation only for silver polyester and no conduit present any advantage in the presence of PDF. Reinfection seems to be not significantly different for the 5 conduits, and only autogenous veins appear to have a positive correlation with infecting organisms. Conclusion: In situ reconstruction may be considered as first-line treatment. Our results suggest that silver polyesters appear to be most appropriate for older patients, and in order to limit reinfection, autogenous veins are probably the most suitable conduit.

Objective: To determine the most appropriate indication for total resection (TR) or partial resection(PR) of infected aortic grafts.Methods: A meta-analysis was conducted on the rates of early/late mortality, amputations and reinfection. A meta-regression was performed with 8 variables: patient age, male prevalence, presence of prosthetic duodenal fistula (PDF), presence of virulent or nonvirulent organisms, urgency, omentoplasty and follow-up.Results: For TR and PR, the rates of early mortality and reinfection were 16.8% and 10.5%, 11% and 27% respectively.For TR, the rates of early mortality and reinfection for in situ reconstruction with allografts and veins were 23% and 10.7%, 10.5% and 2.8% respectively.For TR, urgency, male gender and omentoplasty all had a negative correlation with early mortality. Omentoplasty had a positive correlation with late mortality. Male gender, PDF and virulent organisms had a negative correlation with reinfection, whereas nonvirulent organisms had a positive correlation. Presence of PDF and follow-up had a negative correlation with amputation, whereas male gender had a positive correlation. For PR, no statistical correlation was analyzable except a negative correlation between PDF and reinfection.Conclusion: For TR, operative mortality increases in males, and in emergencies, so total removal of the infected aortic graft seems not advisable, and alternative interventions should be considered. With regard to the risk of reinfection, TR appears recommendable in the presence of nonvirulent infectious organisms, but there is increased risk in the presence of virulent organisms and PDF, and so other optimal options may be discussed.For PR results were not analyzable except for a negative correlation in the presence of PDF.

Introduction L’infection urinaire est une des infections bacteriennes les plus frequentes en ville. E.coli est l’espece bacterienne la plus isolee. Le but de cette etude est de determiner la place des autres enterobacteries dans les infections urinaires en ville, leur repartition en fonction de l’hebergement des patients et comparer les taux de resistance aux antibiotiques (ATB) a visee urinaire et aux cephalosporines de troisieme generation. Materiels et methodes Recueil de tous les antibiogrammes a partir des ECBU realises dans les laboratoires de biologie medicale en 2018. Les antibiogrammes provenant des etablissements de sante prives et publics ont ete exclus. Description de l’epidemiologie bacterienne des infections urinaires en ville et de la resistance des enterobacteries aux ATB suivants : fosfomycine (FOS), nitrofurantoine (FUR), cotrimoxazole (SXT), mecillinam (MEC), cephalosporines de 3e generation (C3G). Resultats Nous avons analyse 229 844 antibiogrammes de souches urinaires. Escherichia coli est l’espece bacterienne majoritairement retrouvee (86,8 % N = 199 465) puis Klebsiella pneumoniae (8,6 % N = 19 803). Les autres enterobacteries representent moins de 5 %. La repartition des enterobacteries varie de facon significative en fonction de l’hebergement (milieu communautaire versus EHPAD). La proportion de souches d’E.coli est significativement plus elevee en milieu communautaire qu’en EHPAD (86,9 % N = 174 380 vs 83,1 % N = 7036 ; p Moins de 1 % des souches d’E.coli sont resistantes aux FUR (0,6 %) et a FOS (0,9 %). Un peu plus de 7 % d’E.coli sont resistantes au MEC, pres de 20 % au SXT et 3,2 % aux C3G. Les souches de Klebsiella spp sont plus resistantes aux ATB (25 % aux FUR, 20 % a FOS, 23 % au MEC, 10,8 % au SXT et 8 % aux C3G). La resistance d’E.cloacae aux FUR est de 15,9 %, a FOS 22,9 % et au SXT 17,3 %. Seulement 6 % des souches d’E.cloacae sont resistantes au MEC alors que 29 % des souches sont resistantes aux C3G. Conclusion E.coli reste la principale espece bacterienne isolee dans les infections urinaires en milieu communautaire (86,9 %) et en EHPAD (83,1 %). Des differences significatives de la repartition des autres enterobacteries en fonction de l’hebergement ont ete observees. Les souches de Klebsiella et d’E.cloacae, plus frequemment isolees en EHPAD, sont plus resistantes aux C3G et aux autres ATB. Une surveillance reguliere de l’epidemiologie des infections urinaires en EHPAD non adosse a un etablissement sanitaire est indispensable pour une prescription rationnelle des ATB et une amelioration de l’hygiene dans ces structures.