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We conducted a retrospective study on hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli (STEC) in 96 adults enrolled in the cohort of the National Reference Center for Thrombotic Microangiopathies network in France during 2009-2017. Most infections were caused by STEC strains not belonging to the O157 or O104 serogroups. Thirty (31.3%) patients had multiple risk factors for thrombotic microangiopathy. In total, 61 (63.5%) patients required dialysis, 50 (52.1%) had a serious neurologic complication, 34 (35.4%) required mechanical ventilation, and 19 (19.8%) died during hospitalization. We used multivariate analysis to determine that the greatest risk factors for death were underlying immunodeficiency (hazard ratio 3.54) and severe neurologic events (hazard ratio 3.40). According to multivariate analysis and propensity score-matching, eculizumab treatment was not associated with survival. We found that underlying conditions, especially immunodeficiency, are strongly associated with decreased survival in adults who have hemolytic uremic syndrome caused by STEC.

BackgroundAcute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not precisely known. The aim of this study was to describe the epidemiology of viral and intracellular respiratory pathogens in children with SCD presenting with fever and/or ACS.Materials and methodsAn observational, prospective, single-centre cohort study with nested case–control analysis was conducted on children with SCD admitted from October 2016 to October 2017 for fever and/or ACS to the paediatric department of Robert Debré university hospital, Paris, France. They were screened for 20 respiratory pathogens by a multiplex PCR in the nasopharynx (FilmArray).ResultsWe included 101 children. M/F sex ratio of 0.45. The median age was 3.2 years (IQR: 1.4–8.2). At least one pathogen was isolated in 67 patients (67%). The most frequent viruses were as follows: rhinovirus (n=33), adenovirus (n=14), respiratory syncytial virus (n=13) and parainfluenza viruses (n=11). Mycoplasma pneumoniae was detected in one case. Twenty-three (23%) presented with or developed ACS. A nested case–control analysis was performed, after pairing ACS with non-ACS children for age and inclusion period. There was no statistical association between any viral detection or multiple viral infection, and ACS (p=0.51) even though parainfluenza viruses were twice as common in ACS.ConclusionsViral detection in febrile children with SCD is frequent, but its association with ACS was not demonstrated. In this study, M. pneumoniae was rare in young children with SCD experiencing ACS.

International audience; The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure. Key Contribution: We review here the current understanding of the mechanisms of virulence of Shiga toxin-producing Escherichia coli; in particular how infection can lead to thrombotic microangiopathy and acute kidney injury. A modern procedure for differential diagnosis is also provided.

OBJECTIVES Thrombotic microangiopathy syndromes are a heterogeneous group of severe diseases that often require ICU admission. Prompt initiation of targeted therapies is required for atypical hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, whereas there is no specific consensus therapy for Shiga toxin-associated hemolytic uremic syndrome. We sought to compare the characteristics of Shiga toxin-associated hemolytic uremic syndrome, atypical hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura patients at admission in the ICU to allow early differentiation of Shiga toxin-associated hemolytic uremic syndrome from other thrombotic microangiopathy syndromes and help to tailor initial treatment. DESIGN Retrospective cohort study. SETTING Two ICUs part of the French reference center for thrombotic microangiopathy syndromes. PATIENTS Adult patients presenting with features of thrombotic microangiopathy syndromes. Other causes than Shiga toxin-associated hemolytic uremic syndrome, atypical hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura were excluded. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS From September 2003 to January 2017, 236 thrombotic microangiopathy syndrome patients were admitted, including 12 Shiga toxin-associated hemolytic uremic syndrome, 21 atypical hemolytic uremic syndrome, and 91 thrombotic thrombocytopenic purpura. Shiga toxin-associated hemolytic uremic syndrome patients were older than other thrombotic microangiopathy syndromes patients (64 yr [interquartile range, 50-72 yr] vs 42 yr [31-54 yr]; p = 0.007) and presented with more frequent digestive symptoms (92% vs 42%; p < 0.001), especially nonbloody diarrhea and vomiting. Biologically, Shiga toxin-associated hemolytic uremic syndrome patients displayed higher fibrinogen (490 mg/dL [460-540 mg/dL] vs 320 mg/dL [240-410 mg/dL]; p = 0.003) and creatinine levels (2.59 mg/dL [2.12-3.42 mg/dL] vs 1.26 mg/dL [0.61-1.90 mg/dL]; p < 0.001), and less marked anemia (hemoglobin level, 9.7 g/dL [8.7-11.9 g/dL] vs 7.7 g/dL [6.3-9.1 g/dL]; p < 0.001). Forty-two percent (n = 5) required renal replacement therapy, and 83% (n = 10) were treated with plasma exchange before the distinction from other thrombotic microangiopathy syndromes could be made. CONCLUSIONS Adult Shiga toxin-associated hemolytic uremic syndrome patients are older, present more frequently with digestive symptoms and display higher hemoglobin and fibrinogen levels than other thrombotic microangiopathy syndromes. However, overlap across the three thrombotic microangiopathy syndromes remains substantial, putting forward the need to implement early plasma therapy until thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome can be ruled out.

International audience

International audience; Invasive meningococcal disease (IMD) is usually associated with intense inflammatory response that is correlated with severe infection. Corticosteroids may regulate this inflammatory response through an early but transient induction of IL-10 that is suggested to improve the outcome of IMD. We explored the mechanism of action of corticosteroids as an adjuvant treatment to antibiotics. Transgenic mice expressing the human transferrin were infected by a hyperinvasive meningococcal strain and transcriptomic analysis were then performed in the blood for all conditions of infection and treatment. Infected untreated mice, infected antibiotic-treated mice and infected amoxicillin and dexamethasone-treated mice were compared. Treatment using both corticosteroids and antibiotics was associated with differential gene expression in the blood especially in Monocytes-Macrophages pathways. Depletion of these cells in infected mice was associated with a more severe bacterial infection and uncontrolled production of both pro-inflammatory and anti-inflammatory cytokines. Accordingly, children suffering from severe IMD had low counts of monocytes at admission. Our data are in favor of a role of corticosteroids in enhancing a polarization from pro-inflammatory to anti-inflammatory phenotypes of Monocytes-Macrophages axis that may help controlling meningococcal invasive infections.

Shiga toxin-producing Escherichia coli (STEC) infection can cause simple diarrhoea but also life-threatening haemolytic and uraemic syndrome (HUS) in infants. Diagnosis is based on amplification of genes encoding the Shiga toxin ( stx ) on stools.1 The increasing ability to detect STEC due to the availability of multiplex PCR raises questions concerning the interpretation by clinicians of a positive PCR for patients with acute diarrhoea. Therefore, knowledge of the rate of asymptomatic carriage among young infants is needed. We assessed the rate of STEC carriage in a large cohort of children less than 2 years old, at risk of HUS in France, irrespective of their modality of care. This work is an ancillary study of a longitudinal survey of faecal Enterobacterales antimicrobial resistance performed in children aged 6–24 …

Introduction Haemolytic uraemic syndrome (HUS) related to Shiga toxin-producing Escherichia coli (STEC) is the leading cause of acute renal failure in young children. In France, HUS surveillance in children aged Aim We present the results of this surveillance between 2007 and 2016. Methods A voluntary nationwide network of 32 paediatric departments notifies cases. Two national reference centres perform microbiological STEC confirmation. Results Over the study period, the paediatric HUS incidence rate (IR) was 1.0 per 100,000 children-years, with a median of 116 cases/year. In 2011, IR peaked at 1.3 per 100,000 children-years, and decreased to 1.0 per 100,000 children-years in 2016. STEC O157 associated HUS peaked at 37 cases in 2011 and decreased to seven cases in 2016. Cases of STEC O26-associated HUS have increased since 2010 and STEC O80 associated HUS has emerged since 2012, with 28 and 18 cases respectively reported in 2016. Four STEC-HUS food-borne outbreaks were detected (three STEC O157 linked to ground beef and raw-milk cheese and one STEC O104 linked to fenugreek sprouts). In addition, two outbreaks related to person-to-person transmission occurred in distinct kindergartens (STEC O111 and O26). Conclusions No major changes in HUS IRs were observed over the study period of 10 years. However, changes in the STEC serogroups over time and the outbreaks detected argue for continuing epidemiological and microbiological surveillance.

We report a hemolytic uremic syndrome (HUS) case due to Stx2f-producing E. coli illustrating the diagnostic difficulty of this Shiga-toxin subtype. Clinicians should be aware of limits of certain rapid molecular panels that are increasingly being used and may play a role in underestimating the global burden of such infections.

International audience; BACKGROUND: Prodromal symptoms are frequently reported in the atypical form of Hemolytic uremic syndrome (aHUS) suggesting implication of infectious triggers. Some pathogens may also play a role in the mechanisms of production of autoantibody directed against Factor H (FH), a complement regulator, leading to aHUS.METHODS: The presence of 15 gastrointestinal (GI) pathogens was investigated by using xTAG-based multiplex PCR techniques on stools collected at the acute phase in a cohort of Indian HUS children classified according to the presence or absence of anti-FH autoantibodies.RESULTS: Prevalence of pathogens in patients with anti-FH antibody (62.5%) was twice that in those without (31.5%). Different pathogens were detected, the most frequent being Clostridium difficile, Giardia intestinalis, Salmonella, Shigella, Rotavirus, Norovirus and Entamoeba histolytica. No stool was positive for Shigatoxin.CONCLUSION: This study reveals a higher prevalence of GI pathogens in anti-FH positive than in negative patients. No single pathogen was implicated exclusively in one form of HUS. These pathogens may play a role in the disease initiation by inducing complement activation or an autoimmune response.

Extra-intestinal complications of Salmonella Typhi (S. Typhi) infections usually occur in endemic countries and in patients with underlying risk conditions. A 14-year-old immunocompetent girl was admitted with respiratory distress owing to S. Typhi pneumonia and pleural empyema. She was a native of Ivory Coast but had lived in France for 4 years and had not travelled abroad for several years. There were no gastro-intestinal symptoms and no S. Typhi carriage was detected in her family. She recovered completely with ceftriaxone and ciprofloxacin and pleural drainage was not required. An atypical presentation of S. Typhi should be considered even in settings where there are no risk factors.

Objectives The objective of this study was to evaluate the evolution and risk factors of ESBL-producing Enterobacteriaceae (ESBL-E) carriage in children in the community for a long period distinguishing ST131 and non-ST131 Escherichia coli. Patients and methods In this prospective study, rectal samples were obtained from children aged 6-24 months by community paediatricians between 2010 and 2015. Demographic characteristics and risk factors for ESBL-E carriage were collected. Distribution of β-lactamase genes, phylogenetic groups, ST131 and virulence factors of resistant E. coli was determined. Results We enrolled 1886 children; 144 (7.6%) harboured ESBL-E, and this rate increased from 4.8% to 10.2% between 2010 and 2015. Risk factors for ESBL-E carriage were being cared for at home [adjusted OR (aOR) = 1.8, 95% CI = 1.1-2.9], recent antibiotic use (aOR = 1.5, 95% CI = 1.0-2.1) and travel history (aOR = 1.7, 95% CI = 1.1-2.6). Among patients carrying ESBL, E. coli (98%) and CTX-M type (90%) predominated and PapGII adhesin, characteristic of pyelonephritogenic E. coli strains, was rare (7%). In 2015, E. coli isolates frequently belonged to the phylogenetic group B2 (48%), and 37% were ST131 compared with 5% in 2010. Compared with non-ESBL-producing strains, ST131 carriage was associated with hospitalization in the last 6 months (aOR = 3.5, 95% CI = 1.4-8.8). Conclusions Between 2010 and 2015, the carriage of ESBL-E in community children doubled because of the massive expansion of the E. coli ST131 clonal group. The risk for carrying ST131 was associated with previous hospitalization, but not, contrary to the counterpart, antibiotic treatment, daycare attendance or travel history.

We performed a cohort study of children who survived bacterial meningitis after the neonatal period at a single pediatric center in France over a 10-year period (1995-2004) to identify predictors of death and long-term neurological deficits in children with bacterial meningitis. We performed multivariate regression to determine independent predictors of death and neurologic deficits. We identified 101 children with bacterial meningitis of which 19 died during initial hospitalization. Need for mechanical ventilation [hazard ratio (HR) 11.5, 95 % confidence interval (CI) 2.4-55.5)] and thrombocytopenia defined as a platelet count150 × 10(9) per liter (HR 0.6, 95 % CI 0.4-0.9) at presentation were associated with death during initial hospitalization. At final assessment, 42 of the 70 survivors had no neurologic deficits identified; 20 had a single deficit, and eight had multiple deficits. A delay in initiation of antibiotics (HR 1.3, 95 % CI 1.1-1.7) and hydrocephalus on computed tomographic scan (HR 2.6, 95 % CI 1.1-6.0) were associated with having one or more long-term neurologic deficits. Identification of children at risk of death or long-term neurologic sequelae may allow therapeutic interventions to be directed to children at the highest risk.

We compare the microbiology of otopathogens causing recurrent acute otitis media (AOM) or AOM treatment failure in 600 children during 2000 to 2008 before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV-7). Streptococcus pneumoniae predominated before PCV-7 introduction and during 2007 to 2008, whereas Haemophilus influenzae predominated during 2005 to 2006. S. pneumoniae 19A became the most frequent serotype after PCV-7 introduction.

Extended-spectrum beta-lactamase (ESBLs) are defined as s-lactamase able to hydrolyze all penicillins and cephalosporins with the exception of cephamycins (cefotixin, cefotetan), moxalactam and carbapenems and are encoded by mobile genes. The most frequently encountered ESBLs belong to the CTX-M, SHV, and TEM families. ESBLs were found first in Klebsiella pneumonia and then predominantly in E. coli. The incidence of patients with ESBLs E. coli increase since 2000 in Robert Debre Hospital in Paris. They were mainly implicated in urinary tract infections and less frequently in other infections such as materno-foetal infections or neonatal meningitis. An increase of consumption of carbapenems may lead to spread of carbapenem resistant organisms. Thus alternative to carbapenems for treatment of ESBL producers are needed.

Since the 1980s, infections due to Streptococcus pyogenes or group A streptococci (GAS) were marked by the increase in invasive infections and the emergence of clones which were resistant to macrolides. Those challenges led the French national reference center for streptococci to enhance the epidemiological survey and the characterization of GAS strains, in collaboration with the National Institute for Public Health Surveillance. Active surveillance is of major importance for implementation of therapeutic and prophylactic guidelines and for evaluation of future streptococcal vaccines.

Resume Introduction La vancomycine represente actuellement, chez l’enfant comme chez l’adulte, le traitement de premiere intention des infections severes a Staphylococcus aureus et a staphylocoque a coagulase negative resistant a la methicilline (SARM) d’origine communautaire ou nosocomiale. Le dosage du taux residuel sanguin (TR) est essentiel pour prevenir le risque de sous-dosage ou surdosage. Objectif Le but de ce travail est de rapporter les taux sanguins initiaux de vancomycine realises au moment du TR avant ajustement eventuel de la prescription au cours d’une periode de 10 ans a l’hopital Robert-Debre dans le service de microbiologie. Patients Un total de 3759 enfants âges, de 1 mois a 15 ans, et 358 nouveau-nes a ete etudie. Methodes Les dosages ont ete realises par la methode de polarisation de fluorescence. Les concentrations minimales inhibitrices (CMI) ont ete determinees par la methode du E-test. Resultats et conclusion Sur les 3759 enfants âges, de plus de 1 mois, 2059 (55 %) avaient des TR insuffisants ( 15 mg/L). Chez les 358 nouveau-nes, 43 % avaient des TR inferieurs a 10 mg/L et 31 % des TR superieurs a 15 mg/L, potentiellement toxiques. Sur l’ensemble des patients, 425 ont eu a la fois la mesure du TR et la determination de la CMI de la vancomycine pour la souche presumee responsable de l’infection. Le rapport TR/CMI etait initialement inefficace car inferieur a 4 chez 50 % des patients et superieur a 10 chez 5 % des patients. La surveillance des TR dans le suivi therapeutique des enfants ayant une infection a S. aureus ou a SARM est indispensable pour optimiser le traitement.

Since the 1980s, Shiga toxin-producing Escherichia coli (STEC), especially E. coli O157:H7, has been an important cause of food borne disease in industrial countries. In France, as there was no routine screening for STEC in clinical laboratories, enhanced surveillance of hemolytic uremic syndrome (HUS) in children less than 15 years of age was established in 1996 to monitor trends in the incidence of STEC infections.The surveillance system was based on a voluntary national network of pediatricians of 31 pediatric nephrology units in public hospitals.From 1996 to 2006, the mean annual incidence of HUS was 0.71 cases per 100,000 children less than 15 years of age and 1.87 cases per 100,000 children less than 5 years of age. STEC infections were confirmed in 66% of patients; STEC O157 was the most common serogroup identified in STEC-related HUS (83%). In this 11-year period, 96% of HUS cases were sporadic and only 2 outbreaks caused by STEC O157 and by a dual infection of STEC O26 and O80 were detected.An evaluation of the surveillance of pediatric HUS showed that it is a simple and useful system for monitoring trends in STEC infections in France. It provides the information needed to measure the impact of new and changing vehicles of STEC transmission, and evaluate the effectiveness of prevention measures.

UNLABELLED Congenital malaria is uncommon in nonendemic countries. We describe two cases involving neonates hospitalized with fever, anaemia and thrombocytopaenia. Thick and thin blood smears were positive for Plasmodium vivax (P. vivax) and P. ovale, respectively. These two cases were discussed regarding the literature and potential implications of HIV coinfection in the mother. CONCLUSION Consistent data in the literature suggest that peripheral blood films should be performed in HIV-positive women who travelled to an endemic area or with a history of malaria prior to gestation. With today's travelling patterns, congenital malaria should be considered as an important differential diagnosis of neonatal sepsis.

UNLABELLED Acute ethmoiditis are bacterial infections of ethmoid sinuses, which may spread to the orbital or the endocranial spaces. It is essential to fit the antibiotherapy to the bacteria responsible for these infections. POPULATION AND METHODS The charts of children hospitalized from 1995 to 2003 for an acute ethmoiditis were reviewed, particularly the results of bacterial exams and the antibiotics delivered. RESULTS Over this 9-year period, 125 children (mean age 4.5 years) were hospitalized for acute ethmoiditis. Eighty were checked for blood cultures, which were sterile in 73 cases, and in the other cases, grew Staphylococcus, S. Pneumoniae or Streptococcus pyogenes. Seric soluble antigens were absent in the 5 cases where they were looked for. Ten children had a puncture of a subperiostal abscess: it was sterile in 5 cases, Staphylococcus was found in 4 cases, S. pneumoniae in the last case. Most children received an association of cefotaxim and fosfomycine for a mean duration of 5.6 days. Thirteen per cent of the children received 3 or 4 antibiotics. DISCUSSION It is always difficult to found the bacteria responsible for an acute ethmoiditis. In our serie as in others, the most frequent bacteria were Staphylococcus, S. pneumoniae and S. pyogenes. CONCLUSION In view of the bacteria responsible for these infections and their antibiotic resistance, we suggest the association of cefotaxim and fosfomycin for the first line of treatment of acute ethmoiditis.

Ureaplasma urealyticum and Mycoplasma hominis colonized 20-40% of newborns and are more frequent in premature. They are responsible for localized infections such as pleural effusion, pneumopathy, adenopathy, abscess or systemic sepsis. An important hyperleukocytosis is often associated with pulmonary infections. Their responsibility, as pathogen agents, is questionable in some non bacterial meningitis. There is large controversy for their role as cofactor, in chronic lung disease (bronchopulmonary dysplasia) and periventricular leukomalacia, because of a too low number of newborns in prospective trials. Genital mycoplamas are resistant to beta lactamines. Macrolides have a good sensitivity, particularly josamycine, but Mycoplasma hominis is resistant to erythromycin. For systemic sepsis, fluoroquinolones such as ciprofloxacine have less deleterious effects than IV erythromycin.

Resume Objectif Les recommandations actuelles proposent de ne traiter par antibiotique que les seules angines a streptocoque β-hemolytique du groupe A (SGA) dont le diagnostic repose sur la realisation de tests de diagnostic rapide. L’antibiotherapie empirique doit reposer sur les etudes epidemiologiques actualisees de la resistance due aux antibiotiques. Le but de notre etude a ete d’evaluer l’activite des antibiotiques actuellement preconises dans le traitement des angines aigues a SGA. Methode La penicilline G, l’amoxicilline, le cefaclor, le cefpodoxime, le cefuroxime, l’erythromycine, la clarithromycine et la clindamycine ont ete testes sur 93 souches consecutives de SGA isolees d’angine aigue en 2002. Les CMI 50 et 90 des antibiotiques ont ete determinees par la methode de dilution en milieu gelose (CA-SFM). Les genes de resistance aux macrolides (ermA, ermB, mefA) ont ete recherches par PCR. La diversite genetique des souches resistantes a l’erythromycine a ete analysee par pulsotypie apres traitement par Smal (logiciel Finger-printing II-Biorad). Resultats L’activite des β-lactamines testees est comparable et aucune resistance a l’egard de ces molecules n’a ete observee (0 %). En revanche, cette etude confirme l’emergence de la resistance aux macrolides chez le SGA, avec une augmentation de la resistance a l’erythromycine en 2002 de 14 % par rapport a une etude anterieure menee en 1996-99. Conclusion L’optimisation du traitement empirique dans les angines aigues doit tenir compte, d’une part, du risque eleve d’echec d’eradication du SGA associe a la resistance in vitro a l’erythromycine et a la clarithromycine, d’autre part de la sensibilite comparable des differentes β-lactamines. Ces resultats renforcent les recommandations d’utilisation des β-lactamines en premiere intention dans le traitement de l’angine aigue a SGA.

Candida infections in newborns are classified, as bacterial ones, in early onset or maternofoetal infections and late onset diseases, primitive and nosocomial. Candida infections are responsible of less than 1% of early onset sepsis. Their diagnosis is facilitated by suggestive cutaneous lesions which can be associated or not with systemic infection. Candida nosocomial infections are the most frequent, 7% in premature infants < 1500 g; they are associated with a central venous catheter or with cutaneous infection in extremely low birth weight infants. C. albicans is the predominant species in maternofoetal infections, contrary to nosocomial ones where C. parapsilosis is predominant, 60%. Both species are sensitive to fluconazole. Amphotericin B and its lipidic derivative Ambisome is the reference drug. Because of its lower toxicity and simplicity of administration, fluconazole is preferable for sensitive species. Its prophylactic use in colonized premature infants has been recently proposed.

Objectives:To investigate and describe an outbreak ofBurkholderia cepaciain a neonatal intensive care unit (NICU) and a pediatric intensive care unit (PICU), and to report the interventions leading to the cessation of the outbreak.Design:We conducted an epidemiologic investigation of an outbreak ofB. cepaciacolonization or infection in two clinical wards during a 35-month period (December 1998 to October 2001).Setting:A 500-bed, university hospital-affiliated, tertiary-care pediatric institution in Paris, France, with a 22-bed PICU and 31-bed NICU.Methods:Ribotyping was used to determine the genotypes ofB. cepaciaisolates. Procedures for the maintenance and disinfection of respiratory therapy devices were reviewed.Results:Thirty-two children were colonized (n = 14) or infected (n = 18) byB. cepaciain 2 wards (28 in the PICU and 4 in the NICU). In the PICU, a single ribotype was found among the isolates obtained from all of the patients except 1, and from the 6 isolates obtained from respiratory therapy devices (ie, heated humidifier water). In the NICU, the isolates obtained from the patients harbored a single ribotype unrelated to that of the epidemic strain isolated in the PICU; no environmental source of infection was found.Conclusion:Two different outbreaks appeared to be associated with 2 ribotypes, 1 of which was linked to patient-to-patient transmission via respiratory therapy devices. Complete elimination of the outbreak was achieved only when disposable, sterilizable, or easy-to-disinfect materials were used in the PICU. The source of infection in the NICU was not found.

Chronic infection by Pseudomonas aeruginosa (PA) in patients with cystic fibrosis (CF) is preceded by a period of colonization and acute infection. Early aggressive antibiotic treatment of initial colonisation may prevent or at least delay chronic pulmonary infection. We initiated treatment with a combination of IV beta-lactam tobramycin, followed by nebulized colistin when PA was first isolated from patients with CF. Subsequent serial PA isolates obtained from these colonized CF patients were characterized by means of molecular methods to determine whether they were genetically related to the initial strain. Initial colonization was eradicated in all 19 patients. All patients reacquired PA within 3-25 months during the 3 years of follow-up. Fourteen patients acquired a new PA strain with a distinct genotypic profile, suggesting a new source of contamination. Five patients had two PA isolates with identical genotypes, suggesting either previous undetected respiratory tract colonization or a persistent environmental source of contamination.

Rotavirus is the major cause of gastroenteritis in children and the main cause of hospital acquired-infection in paediatric unit. We report the epidemiology of gastroenteritis in our hospital during five consecutive years. Rotavirus was involved in 13% of the patients. Seasonal peaks were observed in January and 45.8% of the patients were less than 6 month old. The rotavirus infection was hospital-acquired in 1/3 of the cases. During the winter period, the incidence of rotavirus nosocomial infection was 4.4%.

International audience; We investigated mechanisms of the false-positive test results on rapid-antigen detection test (RADT) for group A Streptococcal (GAS) pharyngitis. Most RADT false-positives (76%) were associated with polymerase chain reaction-positive GAS results, suggesting that RADT specificity could be considered close to 100%. Finding that 61% of GAS culture-negative but RADT-positive cases were positive on both GAS polymerase chain reaction and Staphylococcus aureus testing, we posit bacterial inhibition as causative.

Extended-spectrum-β-lactamase (ESBL)-producing pathogens are associated with extensive morbidity and mortality and rising health care costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI), and no large studies have examined the impact of cefepime therapy. A retrospective 3-year study was performed at the Detroit Medical Center on adult patients with BSI due to ESBL-producing Klebsiella pneumoniae or Escherichia coli. Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. One hundred forty-five patients with BSI due to ESBL-producing pathogens, including K. pneumoniae (83%) and E. coli (16.5%), were studied. The mean age of the patients was 66 years. Fifty-one percent of the patients were female, and 79.3% were African-American. Fifty-three patients (37%) died in the hospital, and 92 survived to discharge. In bivariate analysis, the variables associated with mortality (P < 0.05) were presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included stay in the intensive care unit (odds ratio [OR], 2.17; 95% confidence interval [CI], 0.98 to 4.78), presence of a central-line catheter prior to positive culture (OR, 2.33; 95% CI, 0.77 to 7.03), presence of a rapidly fatal condition at the time of admission (OR, 5.13; 95% CI, 2.13 to 12.39), and recent prior hospitalization (OR, 1.92; 95% CI, 0.83 to 4.09). When carbapenems were added as empirical therapy to the predictor model, there was a trend between empirical carbapenem therapy and decreased mortality (OR, 0.61; 95% CI, 0.26 to 1.50). When added to the model, receipt of empirical cefepime alone (n = 43) was associated with increased mortality, although this association did not reach statistical significance (OR, 1.66; 95% CI, 0.71 to 3.87). The median length of hospital stay was shorter for patients receiving empirical cefepime than for those receiving empirical or consolidated carbapenem therapy. In multivariate analysis, empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend toward an increased mortality risk and empirical carbapenem therapy was associated with a trend toward decreased mortality risk.

International audience; BACKGROUND:On 22 June 2011, 8 patients with hemolytic uremic syndrome (HUS) or bloody diarrhea were reported in France. All 8 were attendees of a community center event on 8 June near Bordeaux. Three Escherichia coli cases were confirmed by isolation of Shiga toxin-producing E. coli O104:H4 stx2 aggR producing a cefotaximase (CTX-M) β-lactamase (STEC O104:H4); the same rare serotype caused the outbreak in Germany in May-July 2011. An investigation was initiated to describe the outbreak, identify the vehicle for infection, and guide control measures.METHODS:We conducted a retrospective cohort study among all adults attending the event, including food handlers. A standardized questionnaire was administered to participants. A case was an attendee who developed HUS or diarrhea between 8 and 24 June. Cases were confirmed by isolation of STEC O104:H4 or O104 serology. Relative risks (RRs) and 95% confidence intervals (CIs) by exposure were calculated using a Poisson regression model.RESULTS:Twenty-four cases were identified (14% attack rate). Of these, 18 (75%) were women, 22 (92%) were adults, 7 (29%) developed HUS, 5 (21%) developed bloody diarrhea, and 12 (50%) developed diarrhea. Ten (42%) cases were confirmed. Fenugreek was the only sprout type with an independent association to illness (RR, 5.1; 95% CI, 2.3-11.1) in multivariable analysis.CONCLUSIONS:This investigation identified a point-source STEC O104:H4 outbreak associated with consumption of fenugreek sprouts. Comparison of results from French and German STEC O104:H4 outbreak investigations enabled identification of a common food vehicle, fenugreek sprouts, and resulted in implementation of Europe-wide control measures in July 2011.

International audience; Following the outbreak of haemolytic uraemic syndrome (HUS) on June 2011 in south-western France, household transmission due to Escherichia coli O104:H4 was suspected for two cases who developed symptoms 9 and 10 days after onset of symptoms of the index case. The analysis of exposures and of the incubation period is in favour of a secondary transmission within the family. Recommendations should be reinforced to prevent person-to-person transmission within households.

As of 12:00 28 June 2011, 15 cases of haemolytic uraemic syndrome (HUS) or bloody diarrhoea have been identified in the Gironde, south-west France. Investigations suggest the vehicle of transmission was sprouts, served at an event in Begles on 8 June 2011. A strain of shiga toxin- producing Escherichia coli O104:H4 has been isolated from five cases. This strain is genetically related to the strain identified in the recent E. coli O104:H4 outbreak in Germany, and shares the same virulence and antimicrobial resistance characteristics. .

Background: Purulent bacterial conjunctivitis affects all ages with high frequency in newborns and children. In a subset of 150 children included in a large study having enrolled 1043 patients, our aim was to analyze in children, the efficacy and safety of azithromycin 1.5% eye-drops in the treatment of this disease. Methods: This multicenter, randomized, investigator-masked, parallel-group study, included 150 children and adolescents to study safety and compare azithromycin 1.5% eye drops twice daily for 3 days and tobramycin 0.3% 1 drop every 2 hours for 2 days then 4 times daily for 5 days. Out of 150 patients included, 58 had positive cultures and were studied for efficacy. Signs and symptoms were evaluated and cultures obtained at baseline, Days 3 and 9. Primary efficacy variable was the clinical cure (score 0 for bulbar conjunctival injection and purulent discharge) at the test of cure visit (day 9). Results: Both treatments were effective with a clinical and microbiologic cure of more than 80% of children on day 9. Azithromycin therapy provided a greater bacteriologic cure on day 3 than did tobramycin (P < 0.001) and eradicated bacteria that were defined as resistant, using classical antibiogram. No adverse effects were noted on the ocular surface. Conclusions: Azithromycin 1.5% eye drops leads to a rapid clinical and microbiological cure.

In 2001 to 2008, we documented 483 cases of pediatric community-acquired bacteremia mostly because of Streptococcus agalactiae (4 days), Escherichia coli (4 days to 3 months), pneumococci (3 months to 5 years), and Staphylococcus aureus (5 years). Pneumococcal conjugate vaccination affected the serotype distribution of pneumococcal bacteremia but not its frequency. Serotype 19A represented 12% and 22% of pneumococci in the prevaccine and vaccine periods, respectively.

We have used a dynamic in-vitro model to determine the killing kinetics of two formulations of cefuroxime axetil against 18 clinical strains of Haemophilus influenzae. The concentration of cefuroxime axetil was adjusted dynamically to simulate the mean serum profile in healthy volunteers following the administration of a single 250 mg dose in oral suspension or tablet form. Bacterial numbers were reduced by 3 log10 cfu/mL during the eight-hour experimental period with both dosage form simulations. Our results suggest that cefuroxime axetil, 250 mg in oral suspension or tablet form, may protect against the dissemination of H. influenzae during episodes of bacteraemia.

We describe 5 pediatric cases of Neisseria meningitidis serogroup W135 infection. Infectious and/or reactive extrameningeal involvement was frequent. One patient had a persistent postmeningococcal inflammatory syndrome. Four of 5 isolates belonged to the clonal complex 37. The important risk of extrameningeal complications must be borne in mind when treating children with N. meningitidis W135 infection.

Sir: A 10-month-old boy returning from Egypt was admitted to the paediatric department for a 4-day history of fever and diarrhoea. He had a maculopapular rash and a chin furuncle with no history of trauma. A methicillin-susceptible Staphylococcus aureus (MSSA) was cultured from the pus. A first skin biopsy showed cellulitis with superficial necrosis that did not reach the underlying fascia. He received oxacillin, gentamicin, and diarrhoea treatment. After 72 h, he was transferred to the PICU for septic shock. He had a necrotic ulcer on the chin, conjunctivitis, and trunk desquamation (Fig. 1a). Blood tests showed thrombocytopenia, hyponatraemia, hyperlactataemia, liver cytolysis, and renal failure. He received fluids, vasopressors, endotracheal ventilation, analgesia, and four new antibiotics (cefotaxime, vancomycin, rifampin, and metronidazole). The skin lesion spread within 12 h and the oedema extended from the chin to the lower right ear. Because MRI was unavailable, cervical computed tomography was performed after clinical stabilization. Findings suggested necrotizing fasciitis (NF). Emergent surgical debridement showed extensive necrosis reaching the underlying muscles. A new skin biopsy performed during surgery confirmed the diagnosis (Fig. 1b). A new bacteriological sample identified the same MSSA, as shown by chromosomal DNA restriction patterns in pulsed-field gel electrophoresis. PCRs identified genes coding for Panton Valentine leukocidin (PVL); A, H, and K-enterotoxins; and toxic-shock-syndrome toxin-1 (TSST-1). The patient improved rapidly after surgery with drainage for 6 days (Fig. 1c). He was discharged home 3 weeks later with oral antibiotics for a total of 6 weeks. After 1 year, healing was complete with no skin graft (Fig. 1d). Because NF is rare in children, its diagnosis remains challenging [1]. Our patient had no chronic disease or predisposing factors [2]. The incidence of severe pneumonia caused by multiple-toxin-secreting MSSAs seems to be rising in paediatric patients [3]. However, NF caused by MSSAs producing both PVL and

Background and aims: Acute bacterial meningitis is a life-threatening illness with possible long-term neurocognitive sequelae. Aim of the study was to identify clinical and biological factors associated with death or neurological sequelae in a retrospective cohort of children with bacterial meningitis. Methods: Retrospective cohort study. Inclusion criteria were bacterial meningitis beyond 1 month of age; and death or long-term (>10 yrs) follow-up. Clinical and biological data at admission were retrieved from medical charts. Results: Eighty-nine patients (age at diagnosis 1 month - 15 years) were enrolled between 1990 and 1999. Nineteen (21%) died, two of them suffered from chronic diseases. At diagnosis, the following variables were associated with survival: absence of seizures (p 12 (p 150,000/mm3 (p 5,000 (p 1,500 (p< 0.01), no need for mechanical ventilation (p < 0.001). Among children who survived: 42 (60%) did not show any neurocognitive problems; 15 (21.4%) developed hearing loss, 10 (14.2%) mild mental retardation, 8 (11.4%) motor problems, 6 (8.5%) epilepsy, 2 (2.8 %) sleep disorders. None developed psychiatric disorders. Conclusion: Some factors were significantly associated with survival in children with bacterial meningitis. The overall prognosis was good in more than half of the long-term survivors. The main limit of our study is its retrospective nature. However, since the routine use of vaccines, the incidence of bacterial meningitis has decreased so that prospective studies are difficult to conduct in developed countries.

• To determine the risk of bacteremia during tonsillectomy, we cultured blood specimens that were taken from 32 children during surgery and tonsillar swabs that were obtained just before excision, and compared the results with quantitative cultures of the excised tonsillar tissue. Twenty-five children had Haemophilus influenzae within the tonsillar tissue (density range, 10 3 to 10 8 colony-forming units per gram), and seven had Streptococcus pyogenes (density, 10 3 colony-forming units per gram in one case, 10 5 colony-forming units per gram in one case, and 10 6 colony-forming units per gram in five cases). Twelve perioperative blood cultures were positive; H influenzae was found nine times, and Micrococcus species was found one time, and α-hemolytic streptococci were found two times. Haemophilus influenzae was always present in the corresponding tonsillar specimens, although there was no apparent relationship between the density of colonization of the tonsillar tissue and a positive blood culture. ( Arch Otolaryngol Head Neck Surg. 1992;118:1229-1231)