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Background: We aimed to describe features of Escherichia coli meningitis in a large population of children and the molecular characteristics of the involved strains to determine factors associated with severe disease or death., Methods: Between 2001 and 2013, a prospective national survey collected data for 325 children hospitalized with E. coli meningitis. The national reference center genetically characterized 141 isolates., Results: Among the 325 cases, 65.2% were term, 22.4% late preterm, and 12.5% very/extremely preterm infants. Escherichia coli meningitis was 7-fold more frequent in preterm than term infants. Median age at diagnosis was 14 days; 71.1% of infants were neonates, with 2 peaks of infection at age 0-3 days (mostly preterm neonates) and 11-15 days (mostly term neonates); 8.9% were >89 days old. In total, 51.1% patients were considered to have severe disease, and 9.2% died. B2.1 phylogenetic subgroup (56%) and O1 serogroup (27.7%) were the most frequently identified. On multivariate analysis, death was associated with preterm birth (odds ratio [OR], 3.3 [95% confidence interval {CI}, 1.3-8.4], P = .015 for late preterm infants; OR, 7.3 [95% CI, 2.7-20.9], P < .001 for very/extremely preterm infants) and cerebrospinal fluid (CSF) to blood glucose ratio <0.10 (OR, 15.3 [95% CI, 1.8-128.3], P = .012). Death was associated with uncommon O serogroup strains (P = .014) and severe disease with O7 serogroup (P = .034) and PapGII adhesin (OR, 2.3 [95% CI, 1.2-4.5], P = .015)., Conclusions: In this large study of 325 cases of E. coli meningitis, risk factors of severe disease or death were preterm birth, severe hypoglycorrhachia, CSF/blood glucose ratio <0.10, and molecular characteristics of strains, which should help optimize therapeutic management., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: This study aims to analyze the epidemiology of Group A streptococci (GAS) emm-types causing invasive and noninvasive infections in French children., Methods: From September 2009 to May 2011, we analyzed GAS isolates from 585 pharyngitis, 125 invasive infections and, for the first time in France, 32 healthy carriers. M protein gene (emm) typing of the isolates was carried out by a new rapid technique, combining 3 multiplex-polymerase chain reactions (PCRs) coupled to high-resolution melting (HRM) curves, able to detect 13 major emm-types (emm 1, 3, 4, 6, 11, 12, 22, 28, 75, 77, 87, 89 and 102)., Results: GAS belonging to emm-type 1 were more frequently found among invasive infections than among pharyngitis (24.0% vs. 11.5%, P < 0.001); emm 4 and 89 were more common in pharyngitis than in invasive infections (emm-type 4, 17.4% vs. 6.4%, P = 0.002 and emm-type 89, 9.9% vs. 2.4%, P = 0.006, respectively) and emm 3 and 4 were more common in cases of pharyngitis associated with scarlet fever (21.6% vs. 6.0%, P < 0.001 and 29.3% vs. 14.5%, P < 0.001, respectively)., Conclusion: HRM method enables the rapid emm-typing of a large number of isolates in epidemiological studies. Comparison of GAS causing invasive and noninvasive infections in the same population of children displays an unbalanced repartition of emm-types.

Sorbitol-fermenting Escherichia coli O157:[H7] is a particularly virulent clone of E. coli O157:H7 associated with a higher incidence of haemolytic uraemic syndrome and a higher case fatality rate. Many fundamental aspects of its epidemiology remain to be elucidated, including its reservoir and transmission routes and vehicles. We describe an outbreak of sorbitol-fermenting E. coli O157:[H7] that occurred in France in 2011. Eighteen cases of paediatric haemolytic uraemic syndrome with symptom onset between 6 June and 15 July 2011 were identified among children aged 6 months to 10 years residing in northern France. A strain of sorbitol-fermenting E. coli O157:[H7] stx2a eae was isolated from ten cases. Epidemiological, microbiological and trace-back investigations identified multiply-contaminated frozen ground beef products bought in a supermarket chain as the outbreak vehicle. Strains with three distinct pulsotypes that were isolated from patients, ground beef preparations recovered from patients' freezers and from stored production samples taken at the production plant were indistinguishable upon molecular comparison. This investigation documents microbiologically confirmed foodborne transmission of sorbitol-fermenting of E. coli O157 via beef and could additionally provide evidence of a reservoir in cattle for this pathogen., (© 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.)

Group A Streptococcus (GAS) is a human pathogen responsible for a wide range of clinical manifestations. An increase of GAS invasive infections has been described since the mid 1980s. To study the French epidemiology of invasive infections (i) we characterized all GAS invasive strains received at the French National Reference Center for streptococci (CNR-Strep) between 2007 and 2011; (ii) we analyzed the epidemiological data on the corresponding strains. For each strain, emm genotype, superantigen genes and antibiotics susceptibility were determined. Among the 2 603 non redundant invasive GAS strains, 65.1 % (n=1 695) were isolated from blood culture. A streptococcal toxic shock syndrome (STSS) was described in 16.4 % (n=428) of cases, mostly associated with necrotizing fasciitis (NF), pleuropulmonary or osteoarticular infections (p ≤0.001). The case fatality rate was 10.6 %. A total of 102 different emm genotypes were identified. Three emm genotypes predominated, reaching nearly 60 % of the strains: emm 1 (26.7 %), emm 28 (16.4 %), and emm 89 (12.8 %). The proportion of each emm genotype varied according to the year and the age of patients. Among those < 15 years old, the three main genotypes were emm 1 (36.8 %), emm 12 (12.9 %) and emm 4 (9.5 %). The distribution of superantigen genes (SpeA, SpeC and Ssa) was restricted to several emm genotypes. Between 2007 and 2011, the rate of macrolides resistant GAS strains decreased from 7.8 to 5.5 %. emm 1 strains are still the most common especially in most severe clinical manifestations including STSS and NF., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Background: For the past 20 years, three vaccines against the three main bacterial species implicated in meningitis in children have been included in the French vaccine calendar: Haemophilus influenzae b in 1993, 7-valent pneumococcal conjugate vaccine (PCV7) in 2003 (replaced by 13-valent in 2010) and Neisseria meningitidis C in 2009. The French active surveillance network from the GPIP/ACTIV monitors the change in the epidemiological, clinical, and biological features of bacterial meningitis due to vaccine use., Methods: Over a 12-year period, 233 pediatric wards working with 168 microbiology departments throughout France were asked to report all cases of bacterial meningitis., Results: From January 2001 to December 2012, 4808 bacterial meningitis cases were reported. Between 2001 and 2012, the number of pneumococcal meningitis (PM) cases decreased by 23.4%, and by 32.2% for children less than 2 years old. During this period, the proportion of cases attributable to PCV7 and six additional PCV13 types decreased from 63.3% to 8.1% and 83.7% to 32.4%, respectively. In 2012, the main vaccine types (accounting for 25.8% of cases) were 7F (12.2%), 19A (6.8%), and 19F (6.8%), and the most frequent non-vaccine types were 12F (14.9%), 24F (14.9%), 15B/C (6.8%), 22F (6.8%), and 10A (5.4%). In 2012, the rate of strains with decreased susceptibility to cefotaxime/ceftriaxone (MIC>0.5 μg/mL) represented less than 3% of cases, with no identified resistant strain since 2010 (MIC>2 μg/mL). Between 2001 (n=67) and 2012 (n=9), the number of NmC meningitis cases decreased by 87%., Conclusion: With more than 4800 bacterial meningitis cases reported in 12 years, this nationwide survey provides essential information on the microbiological and clinical characteristics of bacterial meningitis (epidemiology or resistance data). These results could lead to changing antibiotic treatment of pneumococcal meningitis before the results of antibiotic susceptibility tests., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

In France, the use of the 7-valent pneumococcal conjugate vaccine (PCV7) lead to an overall significant decrease in PCV7 invasive pneumococcal disease (IPD) incidence. However, the decrease in vaccine serotype prevalence was partially counterbalanced by the serotype replacement phenomenon. In this study, we analyzed the role of the newly described serotype 6C as one of the replacement serotypes. This work was conducted on a large time scale from the early PCV7 era (2002-2003) to the PCV13 era (2010-2011), both on IPD strains recovered from the whole population and nasopharyngeal colonizing strains isolated in infant less than two years, who are known to be the main reservoir for pneumococci. Serotype 6C took advantage over 6A and 6B serotypes, which both decreased over time. A continuous and significant increase in 6C IPD was observed in adults along the study period; in contrast, in children less than two years, only an increase in 6C nasopharyngeal carriage was found, the prevalence of serotype 6C in IPD remaining very low over time. Among 101 6C invasive and colonizing strains studied by MLST, 24 STs were found to be related to three major clonal complexes, CC395, CC176, and CC315. STs related to CC176 tend to disappear after 2009 and were essentially replaced by ST386 (CC315), which dramatically increased over time. This clonal expansion may be explained by the erythromycin and tetracycline resistances associated with this clone. Finally, the decrease observed in nasopharyngeal 6C carriage since 2010, likely related to the PCV13 introduction in the French immunization schedule, is expected to lead to a decrease in 6C IPD in adults thereafter.

Forty-one children hospitalized for necrotizing pneumonia were retrospectively analyzed. Necrotizing pneumonia represented 0.8% of community-acquired pneumonia and 6% of hospitalized community-acquired pneumonia. The chest radiograph revealed necrosis on admission in onethird of cases. Twenty-one cases (51%) were documented, including 13 Staphylococcus aureus, all Panton-Valentine leukocidin positive, 7 Streptococcus pneumoniae and 1 Fusobacterium nucleatum.

The purpose of this investigation was to describe the clinical and biological characteristics and evolution of invasive Fusobacterium infections in children admitted to two French paediatric tertiary care centres. Children who were admitted from 1998 to 2009 to two tertiary care centres for invasive Fusobacterium infection were included in a retrospective study. Thirty-one children with a median age of 5.7 years (interquartile range, IQR [2.3; 9.3]) were included. Nine children had an underlying condition, most commonly sickle cell disease (n = 3) or immunodeficiency (n = 3). Two children had skin effraction prior to the infection. The major sites of infection were the head and neck (n = 14) and abdomen (n = 10). Three children suffered from atypical Lemierre's syndrome. More than half of the children had a bacterial co-infection (58 %). Six children were hospitalised in an intensive care unit, and 67 % of them had a chronic underlying disease. None of the children died. Six children with negative cultures had Fusobacterium identified through 16S RNA-PCR. Fusobacterium is responsible for severe infection in children. Microbiological diagnosis might be improved by the wider use of molecular detection.

From 2001 to 2008, 119 pediatric cases of meningococcal disease caused by serogroup W were reported in France. They cases represented 4% of all meningococcal disease cases in children and were mostly in infants (54%). Meningitis occurred in 78 (66%) patients but differed by isolate. Isolates of the clonal complex sequence type-22 were associated with nonmeningeal presentation. Further investigations of clinical tropism of meningococcal W isolates are warranted.

Maternal-fetal Escherichia coli infections, such as neonatal bacteremia and meningitis, are important causes of morbidity and mortality. From 2006 to 2010, we studied newborns and their mothers who were colonized with E. coli in a French hospital in order to document (i) the epidemiology and genetic characteristics of extended-spectrum-beta-lactamase (ESBL)-producing E. coli strains, (ii) the prevalence of associated virulence genes, (iii) the prevalence of clone sequence type 131 (ST131), and (iv) the genetic relationship among ESBL-producing strains. Among the 2,755 E. coli cultures recovered from vaginal or neonatal samples, 68 were ESBL producers (2.46%). We found a wide diversity of ESBL genes, with the majority being bla(CTX-M-14), bla(CTX-M-1), and bla(CTX-M-15), distributed among the 4 main phylogenetic groups. Genes encoding virulence factors were found in 90.7% of the isolates, with ≥ 2 virulence genes present in 76% of cases. The prevalence of ST131 among ESBL-producing E. coli isolates was 9.4% (6/64). Five of these 6 ST131 isolates possessed bla(CTX-M-15) enzymes (and also were resistant to quinolones), and one possessed bla(CTX-M-2) enzymes. Two possessed virulence genes, suggesting the presence of pathogenicity island IIJ96 (PAI IIJ96)-like domains. Pulsed-field gel electrophoresis (PFGE) revealed a high level of genomic diversity overall, except for 3 closely related isolates belonging to clonal group ST131. Repetitive PCR showed that the six ST131 isolates were closely related to ST131 control strains (>95% similarity). This study shows a high prevalence of ESBL-producing E. coli strains and clonal group ST131 in the French maternal-fetal population. These results suggest a widespread distribution of ESBL enzymes in the community and highlight the early transmission between mothers and neonates. These findings are worrisome, especially for this particularly vulnerable population.

We studied the macrolide resistance and serotypes of 585 group A streptococcus (GAS) isolates collected from French children with pharyngitis. Nineteen isolates (3.2%) were erythromycin-resistant and harbored the following resistance genes: 31.6% mef(A), 15.8% erm(A), and 52.6% erm(B). The 19 isolates included 7 different emm types (4, 1, 11, 2, 28, 12, and 77) and 7 corresponding multilocus sequence types. The current fall in macrolide consumption has led to a very low rate of GAS macrolide resistance., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Nosocomial outbreaks of extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae are an increasing concern in neonatal intensive care units (NICUs). We describe an outbreak of ESBL-producing K. pneumoniae that lasted 5 months and affected 23 neonates in our NICU. Proton pump inhibitor and extended-spectrum cephalosporin exposure were significantly associated with the risk of ESBL-producing K. pneumoniae colonisation and/or infection. Thirty isolates recovered from clinical, screening and environmental samples in the NICU were studied by means of Raman spectroscopy, pulsed-field gel electrophoresis and repetitive extragenic palindromic polymerase chain reaction (rep-PCR). The Raman clustering was in good agreement with the results of the other two molecular methods. Fourteen isolates belonged to the Raman clone 1 and 16 to the Raman clone 3. Molecular analysis showed that all the strains expressed SHV-1 chromosomal resistance, plasmid-encoded TEM-1 and CTX-M-15 β-lactamases. Incompatibility groups of plasmid content identified by PCR-based replicon typing indicated that resistance dissemination was due to the clonal spread of K. pneumoniae and horizontal CTX-M-15 gene transfer between the two clones.

Background: Since 2001 in France, a nasopharyngeal carriage study was set up for children six to 24 months old. Any data are available for older children (25 to 60 months). The aim of this study is to compare the nasopharyngeal carriage in children with acute otitis media (AOM) or healthy between both age groups (6/24 months versus 25/60 months). Moreover, during the study period, the 13-valent pneumococcal conjugate vaccine (PCV13) has replaced PCV7 in June 2010., Methods: From October 2010 to June 2011, 58 pediatricians obtained nasopharyngeal swabs from children 6-60 months with acute otitis media (AOM) or healthy controls, to analyse the carriage of pneumococcus, Haemophilus influenzae, Moraxella catarrhalis, group A streptococcus and Staphylococcus aureus., Results: Of the 1557 enrolled children, 1258 were 6 to 24 months old (315 healthy and 943 AOM) and 299 were 25 to 60 months (102 healthy and 197 AOM). More then 85% were PCV7 vaccinated and the children of 25/60 months were rarely PCV13 vaccinated (14.1%) compared to younger children (69.9%, P<0.001). For children 6/24 months, the Streptococcus pneumoniae carriage was higher in AOM group (57.3%) versus healthy (28.9%). By contrast for older children, the difference (58.4% versus 50%) was not significant. In the healthy group, older children carried more often S. pneumoniae than younger children (50% versus 28.9%, P<0.0001). This trend was also observed for H. influenzae carriage (49% versus 18.7%, P<0.0001). Multivariate analysis in the healthy group showed that siblings and day care center (or school) increased the carriage of S. pneumoniae and H. influenzae., Conclusion: These data from nasopharyngeal carriage in children 6 to 60 months old showed that pneumococcus and H. influenzae carriage is high for patients under 2 years, especially in the healthy group. Moreover, these data from the transition PCV7/PCV13, will serve as baseline in France to evaluate the impact of PCV13., (Published by Elsevier SAS.)

Streptococcus pneumoniae is an uncommon cause of osteoarticular infections (OAI) in children. The objective of this study was to investigate the clinical and laboratory characteristics of pneumococcal OAI before and after the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7). Data were retrospectively collected from children aged <16 years who were hospitalized for pneumococcal OAI between 1997 and 2007 in four Parisian teaching hospitals. Forty-three children were included (32 with arthritis and 11 with osteomyelitis) and the median age of these children was 12.5 months (range 3 months to 14 years). Serotypes were available for 19/43 strains (44 %) from 1997 onwards and for 12/13 strains (92 %) from 2005 onwards. Seven unvaccinated children were infected with vaccine serotypes and we observed only one vaccine failure. After the introduction of PCV7, we noted an increase in short-term complications and the emergence of serotype 19A, which was penicillin-intermediate in 86 % of cases. After PCV7 introduction, serotype 19A was the most frequent serotype implicated in pediatric pneumococcal OAI. The 13-valent pneumococcal conjugate vaccine introduced in France in June 2010 should cover the emerging serotype.

Background: The GPIP/ACTIV (Groupe de Pathologie Infectieuse Pédiatrique and Association Clinique et Thérapeutique Infantile du Val de Marne) set up an active surveillance network to analyze the epidemiological, clinical and biological features of meningococcal meningitis., Methods: French pediatric wards working with 166 microbiology laboratories enrolled all children (0-18 years old) with bacterial meningitis. Risk factors, signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments and case fatality rate were recorded., Results: Since 2001, 1661 meningococcal meningitis were reported among 3769 (44.1%) bacterial meningitis. Mean age was 4.4- year- old (± 4.8, median 2.5) and 2/3 cases occurred in children under 5- year- old (68.8%). Serogroup B (61.3%) is preponderant following by serogroup C (27.0%). 27.5% of children had received an antibiotic treatment 24 hours before lumbar puncture. A shock is reported in 31.0% of cases. No cases of meningococcal meningitis C has been reported in children vaccinated with a conjugate vaccine. Two children vaccinated with MenBvac(®) vaccine had a meningitis B14:P1.7,16. Global case fatality rate was 6.5% but was higher (9.2%) for serogroup C than for serogroup B (5.9%) (p=0.02)., Conclusion: This is among the largest series of microbiologically documented meningococcal meningitis to date (1661 cases). In France, meningococcal is responsible for approximately 50 % of meningitis. Effective meningococcal serogroup B vaccine and serogroup C vaccination recommendation could control the burden of meningococcal meningitis., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

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.

Background: Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France., Methods: Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies., Results: We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001)., Conclusion: The carriage rates of otopathogen species (Sp, Hi, Mc) and Sa did not significantly change in children with AOM after PCV7 implementation in France. However, we observed significant changes in carriage rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp.

Background: 13-valent pneumococcal conjugate vaccine (PCV13) licensure was based on the immune response (enzyme-linked immunosorbent assay and opsonophagocytic assay) compared with PCV7. National surveillance program of pneumococcal nasopharyngeal (PNP) carriage in children with acute otitis media (AOM) was set up in 2001 when PCV7 was introduced in France and continues to the present. This program was used in 2010-2011 to assess the effect of the implementation of PCV13 on PNP carriage in young children with AOM., Methods: Between October 2010 and March 2011, 58 pediatricians obtained 943 nasopharyngeal swabs from children (6 to 24 months of age) with AOM. The swabs were sent for analysis to the French National Reference Centre for Pneumococci. Demographics, medical history, and physical examination findings were recorded., Results: Among 943 children enrolled (mean age, 13.4 months), 651 had received at least 1 dose of PCV13 and 285 received PCV7 only. Among PCV13-vaccinated children, overall PNP carriage and carriage of serotypes not in PCV7 were significantly lower as compared with children exclusively vaccinated with PCV7 (53.9% vs. 64.6%, P = 0.002 and 9.5% vs. 20.7%, P < 0.0001, respectively). For serotypes 19A, 7F, and 6C, the carriage rates were also significantly lower in PCV13-vaccinated patients than in patients only vaccinated by PCV7: 7.5% versus 15.4%, P < 0.001, 0.5% versus 2.8%, P = 0.002, and 3.7% versus 8.4%, P = 0.003, respectively., Conclusion: In young children (<2 years) with AOM, this study suggests that PCV13 has an impact on overall PNP carriage, as well as on serotypes 19A, 7F, and 6C.

Background: Before 7-valent pneumococcal conjugate vaccine (PCV7) implementation in France, several studies had described the microbiology of acute otitis media (AOM) treatment failures. The causative pathogens were Streptococcus pneumoniae (Sp) followed by nontypable Haemophilus influenzae (NTHi). The aim of this study was to describe the epidemiology of pathogens involved in AOM treatment failures or recurrences., Methods: This French multicentric prospective study enrolled 143 children with AOM treatment failure between 2007 and 2009 observed by 8 ear, nose, and throat specialists. Failure was defined as the persistence of AOM symptoms after at least 48 hours of antibiotic therapy or their recurrence within 4 days after the end of treatment. Standardized history and physical examination findings were recorded, and culture of middle ear fluid (MEF) was obtained., Results: Mean age was 16.9 ± 9.9 months (median, 13.7). Eighty-eight percent of children had received more than 1 dose of PCV7, and 70.6% attended day care. The most common antibiotic used at the time of treatment failure or recurrence was a combination of amoxicillin and clavulanate (51.1%). Bacteriologic sampling demonstrated that in 35% of cases (n=50), no otopathogen was cultured at the time of treatment failure or recurrence. Similar proportions of Sp and NTHi were observed in the 86 patients (60.1%) from whom only a single species was recovered from MEF (46.5% for Sp, n=40 and 45.3% for NTHi, n=39). Among Sp strains, 4.4% were penicillin susceptible, 77.8% were penicillin intermediate, and 17.8% were fully penicillin resistant, and serotype 19A represented 84.5% of all serotypes detected. Among NTHi isolates, 15.5% (n=7) were β-lactamase-producing strains (including 2 strains with only this mechanism of resistance), and strains with reduced susceptibility by changes in protein binding to penicillin (β-lactamase-negative ampicillin resistant strains) represented 35.5% of cases. Among the 50 sterile MEF samples, polymerase chain reaction was performed in 32, of which 4 were positive for HI, 3 for Sp, and 3 for both., Conclusions: Among children with AOM treatment failures in France, Sp and NTHi were equally distributed; 19A was the main Sp serotype, and the main resistance mechanism for NTHi was β-lactamase-negative ampicillin resistance.

Background: Meningococcal meningitis requires rapid diagnosis and immediate management which is enhanced by the use of PCR for the ascertainment of these infections. However, its use is still restricted to reference laboratories., Methods: We conducted an inter-laboratory study to assess the implementation and the performance of PCR in ten French hospital settings in 2010., Results: Our data are in favour of this implementation. Although good performance was obtained in identifying Neisseria meningitidis positive samples, the main issue was reported in identifying other species (Streptococcus pneumoniae and Haemophilus influenzae) which are also involved in bacterial meningitis cases., Conclusions: Several recommendations are required and, mainly, PCR should target the major etiological agents (N. meningitidis, S. pneumonia, and H. influenzae) of acute bacterial meningitis. Moreover, PCR should predict the most frequent serogroups of Neisseria meningitidis according to local epidemiology.

Background: The stability of the accuracy of a diagnostic test is critical to whether clinicians can rely on its result. We aimed to assess whether the performance of a rapid antigen detection test (RADT) for group A streptococcus (GAS) is affected by the clinical spectrum and/or bacterial inoculum size., Methods: Throat swabs were collected from 785 children with pharyngitis in an office-based, prospective, multicenter study (2009-2010). We analysed the effect of clinical spectrum (i.e., the McIsaac score and its components) and inoculum size (light or heavy GAS growth) on the accuracy (sensitivity, specificity, likelihood ratios and predictive values) of a RADT, with laboratory throat culture as the reference test. We also evaluated the accuracy of a McIsaac-score-based decision rule., Results: GAS prevalence was 36% (95CI: 33%-40%). The inoculum was heavy for 85% of cases (81%-89%). We found a significant spectrum effect on sensitivity, specificity, likelihood ratios and positive predictive value (p<0.05) but not negative predictive value, which was stable at about 92%. RADT sensitivity was greater for children with heavy than light inoculum (95% vs. 40%, p<0.001). After stratification by inoculum size, the spectrum effect on RADT sensitivity was significant only in patients with light inoculum, on univariate and multivariate analysis. The McIsaac-score-based decision rule had 99% (97%-100%) sensitivity and 52% (48%-57%) specificity., Conclusions: Variations in RADT sensitivity only occur in patients with light inocula. Because the spectrum effect does not affect the negative predictive value of the test, clinicians who want to rule out GAS can rely on negative RADT results regardless of clinical features if they accept that about 10% of children with negative RADT results will have a positive throat culture. However, such a policy is more acceptable in populations with very low incidence of complications of GAS infection.

Invasive group A streptococcal (GAS) infections cause significant morbidity and mortality. A national survey was initiated to assess the burden of invasive GAS infections in France, describe their clinical characteristics, and assess the molecular characteristics of GAS strains responsible for these infections. The survey was conducted in 194 hospitals, accounting for 51% of acute care hospital admissions in France. Clinical data, predisposing factors, and demographic data were obtained, and all GAS isolates were emm sequence typed. We identified 664 cases of invasive GAS infections, with an annual incidence of 3.1 per 100,000 population. The case-fatality ratio was 14% and rose to 43% in the case of streptococcal toxic shock syndrome. Bacteremia without identified focus (22%) and skin/soft tissue infections (30%) were the most frequent clinical presentations. Necrotizing fasciitis was frequent in adults (18%) and uncommon in children (3%). The 3 predominant emm types were emm1, emm89, and emm28, accounting for 33%, 16%, and 10% of GAS isolates, respectively. The emm1 type was associated with fatal outcomes and was more frequent in children than in adults. Six clusters of cases were identified, with each cluster involving 2 invasive cases due to GAS strains which shared identical GAS emm sequence types. Four clusters of cases involved eight postpartum infections, one family cluster involved a mother and child, and one cluster involved two patients in a nursing home. Invasive GAS infection is one of the most severe bacterial diseases in France, particularly in persons aged ≥ 50 years or when associated with toxic shock syndrome.

Two isolates of enterohemorrhagic Escherichia coli (EHEC) O104:H4 were isolated in France in 2004 and 2009. Both were characterized and compared to the strain which caused the German outbreak in 2011 and to other O104:H4 strains. This suggests that different O104:H4 EHEC strains were present several years prior to the 2011 outbreak.

Rapid identification of metallo-β-lactamase-producing Gram-negative species is crucial for the timely implementation of infection control measures. We describe two pediatric cases in which colonization by VIM-1- and New Delhi metallo-beta-lactamase 1-producing Enterobacteriaceae was rapidly detected by phenotypic and genotypic methods. Phenotypic methods can be useful for routine detection of carbapenemase production.

Background: After the implementation of 7-valent pneumococcal conjugate vaccine (PCV7), in several countries, serotype 19A is now the serotype most frequently involved in pneumococcal diseases and carriage. To determine factors potentially related to 19A nasopharyngeal (NP) carriage we analyzed data from an ongoing prospective French national surveillance study of pneumococcal NP carriage in young children., Methods: NP swabs were obtained from children aged 6 to 24 months, either during routine check-ups with normal findings, or when they presented with acute otitis media (AOM). The swabs were sent for analysis to the French National Reference Centre for Pneumococci. Factors influencing pneumococcal carriage and carriage of penicillin non-susceptible (PNSP), 19A and PNS-19A were investigated by multivariate logistic regression., Results: From 2006 to 2009, 66 practitioners enrolled 3507 children (mean age 13.6 months), of whom, 98.3% of children had been vaccinated with PCV7 and 33.4% of children attended daycare centres (DCC). Serotype 19A was found in 10.4% of the overall population, 20.5% of S. pneumoniae carriers (n = 1780) and 40.8% of PNSP carriers (n = 799). Among 19A strains, 10.7% were penicillin-susceptible, 80% intermediate and 9.3% fully resistant. Logistic regression analysis showed that the main factors associated with PNSP carriage were AOM (OR = 3.09, 95% CI [2.39;3.98]), DCC (OR = 1.70, 95% CI [1.42;2.03]), and recent antibiotic use (OR = 1.24, 95% CI [1.05;1.47]. The main factors predictive of 19A carriage were recent antibiotic use (OR = 1.81, 95% CI [1.42;2.30]), AOM (OR = 1.67, 95% CI [1.11;2.49]), DCC (OR = 1.56, 95% CI [1.21;2.2] and young age, <12 months (OR = 1.51, 95% CI [1.16;1.97])., Conclusion: In a population of children aged from 6 to 24 months with a high rate of PCV7 vaccination coverage, we found that antibiotic exposure, DCC attendance and AOM were linked to 19A carriage.

Background: Neonatal bacterial meningitis remains a severe infectious disease with mortality rates varying between 10% and 15%. The clinical and bacteriologic features of neonatal meningitis collected from January 2001 to December 2007 in a French national survey are presented here., Methods: Cases of neonatal meningitis were prospectively collected by a network of 252 pediatric wards covering 61% of French pediatric wards, associated with 168 microbiology laboratories. Neonatal meningitis was classified as early-onset (d0-d4) and late-onset (d5-d28). Statistical analyses were performed according to gestational age and weight at birth., Results: A total of 444 cases of neonatal bacterial meningitis were reported by 114 pediatric wards. Five cases were excluded from analysis. Group B streptococci (GBS) and Escherichia coli accounted respectively for 59% and 28% of the cases, followed by Gram-negative bacilli other than E. coli (4%), other streptococci (4%), Neisseria meningitidis (3%), and Listeria monocytogenes (1.5%). GBS was the most common pathogen both in early-onset (77% vs. 18% for E. coli) and in late-onset meningitis (50% vs. 33% for E. coli). Among preterm infants, E. coli was more commonly isolated (45% vs. 32% for GBS), especially in very preterm infants (54%). GBS was more often involved in seizures than E. coli (41% vs. 25%). The overall mortality rate was 13% but reached 25% in preterm or small for gestational age infants, regardless of the etiology., Conclusions: GBS was the dominant cause of neonatal bacterial meningitis, with 77% of early-onset and 50% of late-onset cases. E. coli was the most common bacteria in preterm infants.

In France, despite a high rate of pneumococcal conjugate vaccine coverage, the number of cases of pneumococcal meningitis in children did not decline significantly between 2001–2002 (n = 264) and 2007–2008 (n = 244). A decline was observed among children < 2 years old (185 [70.1%] to 134 [54.9%] cases; P = 0.0004), but was counterbalanced by an increase among children ≥ 2 years old (79 [29.9%] to 110 [45.1%] cases). Mean age increased significantly, from 2.3 (median 0.8) to 3.8 (median 1.5) years. After pneumococcal conjugate vaccine 7 implementation, a wide diversity of serotypes implicated in pneumococcalmeningitis was observed; serotypes 19A and 7F were the most frequent.

An outbreak of colonization and infection with an Escherichia coli strain producing extended-spectrum beta-lactamase (ESBL) occurred in a neonatal unit : a high rate of cases was observed, 27/59 neonates were colonized : one of them developed meningitis with favourable outcome and another baby developed conjunctivitis. Despite intensive efforts to control the outbreak by standard methods of hand hygiene, patients screening and isolation, the spread was uncontrolled and the unit was closed to all admission in order to stop the outbreak. The investigation was not able to identify a single outbreak's source. Emergence and spread of ESBL producing E. coli strains from community and hospital acquired infections are a significant public health problem with difficult choice of treatment for serious infections., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

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.

Background: Neisseria meningitidis meningitis represents approximately one-half of the meningococcal cases in French children. To explore the contribution of bacterial typing in improving the management of cases, we aimed to describe clinical characteristics and mortality of meningococcal meningitis in children reported to the multicenter survey system, GPIP/ACTIV, in association with phenotypes/genotypes of bacterial isolates., Methods: From 2001 to 2005, 259 pediatric wards and 168 microbiology laboratories enrolled all children with bacterial meningitis. Risk factors, vaccination status, signs and symptoms, cerebrospinal fluid analysis, treatments and case fatality rate were recorded., Results: A total of 962 cases of Neisseria meningitidis meningitis among a total of 2131 bacterial meningitis (45%) were recorded (mean age, 4.5 +/- 4.7 years). Serogroup distribution of the isolates was 62.3%, 33.7%, 2.9%, 0.6%, and 0.6% for serogroups B, C, W135, A and Y, respectively. The major clonal complexes were ST-41/44 (32.2%), ST-11 (21.9%), ST-32 (20.8%), ST-8 (8.2%), and ST-269 (4.9%). Despite global heterogeneity of the isolates, 2 phenotypes/genotypes were of interest. Isolates of the phenotype/genotype B:14:P1.7,16/ST-32 (56% clustered in the region of Haute Normandie) were observed in older children (8.6 years) and were associated with a higher case fatality rate (12%) than were other phenotypes of serogroup B. The phenotype/genotype C:2a:P1.5/ST-11 was found in 26.3% of serogroup C cases and was possibly associated with a higher mortality among serogroup C (9.9% for C and 5.9% for B, P = 0.04)., Conclusions: This large survey provides data that could be important for implementation of future vaccines. Typing of meningococcal isolates could contribute to an understanding of prognosis in meningococcal meningitis.

Invasive group A streptococcal (GAS) infections have a broad and evolving clinical spectrum, associated with various GAS genotypes and/or virulence factors that are only poorly described in children. We aimed to assess the clinical and molecular characteristics of invasive GAS infections in 28 children admitted from 2000 to 2007 at a large French pediatric tertiary care center. The GAS isolates were characterized molecularly by emm-typing and by the determination of the main virulence factors: speA, speB, speC, smeZ-1, ssa, sic, and silC. The median age of the children was 2.9 years. Osteoarticular infection (OAI) was the main clinical manifestation (n=15/28, 53%). emm-1 predominated (n=10/28), followed by emm-12, 3, and 4. No significant correlation was found between emm type and clinical manifestations, but emm-1 predominated in cases of OAI (n=7/15) and was associated with speA, speB, smeZ-1, and sic virulence factor genes. In this pediatric study, we describe a predominance of OAI associated with emm-1 GAS. Further larger international pediatric studies, including host immunity evaluation, are needed in order to better assess the pathogenesis of GAS infection in children.

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., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

By combining PCR amplification of toxin-encoding genes and sic gene sequencing, we distinguished 24 genotypes among 47 M/emm1 group A streptococci isolated from children and adults in France in 9 cases of infection comprising four clusters and 38 unrelated invasive infection cases used as controls.

With the support of a ministerial program for innovative and expensive technologies, dedicated to the economic evaluation of laboratory diagnosis of pertussis by real-time PCR, external quality assessment for real-time IS481 PCR was carried out. Coordinated by the National Centre of Reference of Pertussis and other Bordetelloses (NCR), this study aimed to harmonize and to assess the performances of eight participating microbiology hospital laboratories throughout the French territory. Between January 2006 and February 2007, 10 proficiency panels were sent by the NCR (ascending proficiency program), representing a total of 49 samples and including eight panels to analyze and evaluate the global sensitivity and specificity of real-time PCR, one to assess the limit of detection, and one to evaluate nucleic acid extraction methods. As part of the descending proficiency program, extracted DNA from clinical samples was sent by the eight participating laboratories in different panels and analyzed by the NCR. In the ascending proficiency analysis, the sensitivity and specificity of the real-time PCR methods were 92.2% and 94.3%, respectively. The limit of detection of the different methods ranged between 0.1 and 1 fg/microl (0.2 to 2 CFU/microl). The nucleic acid extraction methods showed similar performances. During the descending proficiency analysis, performed with 126 samples, the result of the NCR for 15 samples (11.9%) was discordant with the result obtained by the source laboratory. Despite several initial differences, harmonization was easy and performances were homogeneous. However, the risk of false-positive results remains quite high, and we strongly recommend establishment of uniform quality control procedures performed regularly.

On 24-25 October 2005 a cluster of five haemolytic uraemic syndrome (HUS) cases was reported in southwest France. An investigation was undertaken to identify the outbreak source and implement control measures. Cases were defined as individuals with HUS or diarrhoea with isolation of Escherichia coli O157:H7 in stools or a positive antibody response to E. coli O157 lipopolysaccharide, resident in southwest France with symptom onset after 19 September 2005. Sixty-nine identified patients had symptom onset between 5 October and 3 November 2005, including 17 cases of HUS. One brand of frozen beef burgers produced on 22 August 2005 was consumed by all patients in the week before symptom onset. E. coli O157:H7 strains from patients, patients' burgers and the manufacturing plant were genetically related. This is the largest community-wide outbreak of E. coli O157:H7 in France to date and the first associated with consumption of contaminated frozen beef burgers.

A new Escherichia coli virulent clonal group, O45:K1, belonging to the highly virulent subgroup B2(1) was recently identified in France, where it accounts for one-third of E. coli neonatal meningitis cases. Here we describe the sequence, epidemiology and function of the large plasmid harbored by strain S88, which is representative of the O45:K1 clonal group. Plasmid pS88 is 133,853 bp long and contains 144 protein-coding genes. It harbors three different iron uptake systems (aerobactin, salmochelin, and the sitABCD genes) and other putative virulence genes (iss, etsABC, ompT(P), and hlyF). The pS88 sequence is composed of several gene blocks homologous to avian pathogenic E. coli plasmids pAPEC-O2-ColV and pAPEC-O1-ColBM. PCR amplification of 11 open reading frames scattered throughout the plasmid was used to investigate the distribution of pS88 and showed that a pS88-like plasmid is present in other meningitis clonal groups such as O18:K1, O1:K1, and O83:K1. A pS88-like plasmid was also found in avian pathogenic strains and human urosepsis strains belonging to subgroup B2(1). A variant of S88 cured of its plasmid displayed a marked loss of virulence relative to the wild-type strain in a neonatal rat model, with bacteremia more than 2 log CFU/ml lower. The salmochelin siderophore, a known meningovirulence factor, could not alone explain the plasmid's contribution to virulence, as a salmochelin mutant displayed only a minor fall in bacteremia (0.9 log CFU/ml). Thus, pS88 is a major virulence determinant related to avian pathogenic plasmids that has spread not only through meningitis clonal groups but also human urosepsis and avian pathogenic strains.

Serotype 19A Streptococcus pneumoniae strains are now more frequent in French children than before the introduction of a seven-valent conjugate vaccine (PCV7). By applying multilocus sequence typing to 144 serotype 19A isolates collected before and after beginning PCV7 vaccination, we detected clonal expansion of the preexisting penicillin-intermediate sequence type 276.

Background: Development of T-cells based-Interferon gamma (IFNgamma) assays has offered new possibilities for the diagnosis of latent tuberculosis infection (LTBI) and active disease in adults. Few studies have been performed in children, none in France. With reference to the published data on childhood TB epidemiology in the Paris and Ile de France Region, we considered it important to evaluate the performance of IGRA (QuantiFERON TB Gold In Tube(R), QF-TB-IT) in the diagnosis and the follow-up through treatment of LTBI and active TB in a cohort of French children., Methodology/principal Findings: 131 children were recruited during a prospective and multicentre study (October 2005 and May 2007; Ethical Committee St Louis Hospital, Paris, study number 2005/32). Children were sampled at day 0, 10, 30, 60 (except Healthy Contacts, HC) and 90 for LTBI and HC, and a further day 120, and day 180 for active TB children. Median age was 7.4 years, with 91% of the children BCG vaccinated. LTBI and active TB children undergoing therapy produced significant higher IFNgamma values after 10 days of treatment (p = 0.035). In addition, IFNgamma values were significantly lower at the end of treatment compared to IFNgamma values at day 0, although the number of positive patients was not significantly different between day 0 and end of treatment., Conclusions/ Significance: By following quantitative IFNgamma values in each enrolled child with LTBI or active TB and receiving treatment, we were able to detect an increase in the IFNgamma response at day 10 of treatment which might allow the confirmation of a diagnosis. In addition, a decline in IFNgamma values during treatment makes it possible for clinicians to monitor the effect of preventive or curative therapy.

Unlabelled: Listeriosis is a serious invasive disease which affects mainly pregnant women, newborns and immunocompromised adults., Objective: To analyze specifically the epidemiological and clinical data of the meningitis due to Listeria monocytogenes (Lm), from the French Network of Surveillance of Bacterial Meningitis in childhood., Patients and Methods: Patients were aged 0 to 18 years. The diagnosis was based on a combination of a feverish meningeal syndrome and a positive culture of cerebrospinal fluid (CSF) and/or a positive PCR in the CSF and/or positive blood culture associated with a pleiocytose., Results: Among 2539 cases of bacterial meningitis recorded in 6 years (2001 to 2006), 18 cases were due to Lm (0.7 %) (sex ratio M / F : 0.8). The average of age was 2.5 years (median : 0.5 ; ext : 0-15.1). The serotype of Lm was 4B in half of the cases. Most cases have occured in summer and autumn. Two patients presented an acquired or congenital immunodeficiency. Fifty-six percent (n=10) were younger than 1 year, among them, 7 were newborns. The CSF direct microbiologic investigation was suggestive of Lm (Gram positive bacilli) only in two cases, but the culture of CSF was positive for 16 patients and the blood culture was positive for 2 other patients. Three of 18 patients died between 7 and 13 days after admittance : a premature baby of 25 weeks'gestational age, two full-term newborns of 2 days and 1.5 months old. The mortality rate was 16.7 % before the age of 1 year (no death after this age)., Conclusion: Meningitis due to Lm remains a rare disease, including in neonatal period. The recent increase of cases in adults requires to maintain vigilance in children especially since direct examination of CSF can rarely allow the diagnosis.

Objective: The group B streptococcal meningitis (GBS) remains an important cause of child's morbidity and mortality. The purposes of this work were to appreciate the GBS place among the bacterial meningitis, to define clinical and biological factors associated with death and to study the immediate complications., Patients and Methods: This study concerned 276 GBS meningitis listed by the observatory of GPIP/ACTIV on the child's bacterial meningitis in France from January, 2001 to December, 2005. This report is one of the biggest series of child's GBS meningitis published to this day., Results: The GBS was the third germ in frequency responsible for bacterial meningitis at every age (13 %) : 65 % of the GBS meningitis affected infants less than one month of age, 29 % infants between 1 month and 3 months of age and only 6 % infants more than 3 months of age. The male/female ratio in GBS meningitis was nearly equal (51 % vs 49 %). There was no variation of the GBS meningitis number according to the season. The serotype III was mostly involved in this cohort (81 %) followed by the serotype I (13 %). Statistically we observed a significant decline in the number of early onset meningitis from 2001 to 2004 whereas the number of late meningitis and the total meningitis cases were stable. The biological results mostly present in child's GBS meningitis were a high CSF protein level (95 %), a CSF neutrophil count more than fifteen percent (90 %), a low CSF glucose level (83.5 %), leukopenia (49 %) or a normal blood level leukocyte (38 %). Eighty three percent of the children affected by GBS meningitis were term infants. However, the prematurity seemed to be a risk factor to develop late meningitis (age between 7 days and 3 months) and very late meningitis (after 3 months) but no early onset meningitis. Prematurity, convulsions, shock, coma, assisted ventilation, high CSF protein level, weak CSF cell level and leukopenia seemed to be factors associated with death in the GBS meningitis. The mortality of the GBS meningitis was still 14 % and the immediate complications were observed in 62 % of cases, the most frequent being convulsions (45 %)., Conclusion: The GBS meningitis in children remains a frequent problem in pediatrics despite intra partum antibioprophylaxy and thus must encourage to strengthen the prevention of these meningitis.

Objective: To conduct a descriptive analysis of clinical, biological and prognostic aspects of Escherichia coli meningitis in young infants., Methods: Clinical and biological data on young infants diagnosed with neonatal E. coli meningitis (NECM) between 1988 and 2004 were collected retrospectively and analyzed with respect to the isolates'phenotypic and genotypic characteristics. The molecular analyses focused on the phylogenetic group, the sequence-O-type, and genetic virulence traits. The virulence of lethal strains was tested in a newborn rat meningitis model., Results: The median age of the 99 children analyzed was 10 days (0 to 90 days), and 83 of the patients were newborns. Thirty-three children were premature. Hyper- or hypothermia was the most frequent clinical sign at admission. Intercurrent urinary tract infection was present in 28% of cases, all over 6 days of age. 81% of blood cultures were positive. The CSF cytology was abnormal in 97% of cases. Twelve hours after admission, 34% of infants were transferred to intensive care. One-third of transfontanellar ultrasound scans done on admission were abnormal. CSH sterilization was slow in 15 % of cases, despite appropriate antibiotic therapy. The use of ciprofloxacin was associated with more rapid CSF sterilization (94 % vs 77 %, p=0.03). Six children relapsed. The average follow-up was eight months, and 21 % of children had sequelae. The case lethality rate was 14%. Fatal outcome was associated with signs of septic shock (57% vs 3%, p<10(-4)) and neurological failure (76% vs 19%, p<10(-4)) within the first 24 hours, and with abnormalities on the first ultrasound scan (63% vs 27%, p=0.03). The risk of death was higher among children infected by strains belonging to unusual sequence-O-types (50% vs 18%, p=0.01), which harbored fewer virulence factors (4.8 vs 5.9, p<10(-4)). Only aerobactin was less frequent in lethal strains (71 % vs 94%, p=0.02). Strains belonging to unusual sequence-O-types and that were lethal in the animal model induced a significantly lower level of bacteremia than strains belonging to frequent sequence-O-types (p<0.001)., Conclusion: E. coli meningitis remains highly lethal in infants. Clinical and molecular analyses showed a link between lethality and infrequent sequence-O-types. The avirulence of these strains in animal models suggests that fatal outcome could be due to host susceptibility more than to strain virulence.

Background and Method: Group A streptococcal (GAS) invasive infections have been increasingly reported in recent years but meningitis due to GAS remains a rare affection. In children some scarce case reports have been described. The aim of this study was to describe and analyze the clinical and biological data on GAS meningitis recorded in the Bacterial Meningitis (BM) French Surveillance Network (GPIP/ACTIV)., Results: From 2001 through end 2006, 2539 children suffering from proven bacterial meningitis were recorded in the data base. Among them 10 children presented GAS infections. The mean age was 6 years (9 months to 14.1 years) and the sex ratio (male/female) 4/1. Seven out of the 10 patients had a history of community acquired infection before the onset of GAS meningitis : 3 had previous acute otitis media, 1 otitis media with mastoiditis, 2 sinusitis and 1 soft tissue infection. In the 3 remaining children no risk factors of invasive GAS infection could be identified. All but 1 patient survived. The patient who died had no risk factors for invasive infectious disease. He presented with fulminant septicaemia and died 6hours after hospital admission despite appropriate supportive care and prompt antibiotic treatment. The cerebrospinal fluid examination revealed high white blood cells counts (>500/mm(3)) in 8 patients and Gram stained smear showed gram-positive cocci in 6 patients. All the patients received antibiotic regimen including 3(rd) generation cephalosporins before definite bacterial identification and all the strains were susceptible to the first line antibiotic treatment chosen., Conclusion: GAS is an uncommon organism causing meningitis in children. In our study upper respiratory tract infection is the most common predisposing factor for GAS meningitis but even apparently healthy children can suffer from this severe form of bacterial meningitis.

Background: In France, meningococcal meningitis account for 50% of bacterial meningitis in children. The GPIP/ACTIV (Groupe de Pathologie Infectieuse Pédiatrique and Association Clinique et Thérapeutique Infantile du Val de Marne) set up an active surveillance network to analyze the epidemiological, clinical and biological features of meningococcal meningitis., Methods: From 2001 to 2007, 252 French paediatric wards working with 166 microbiology laboratories enrolled all children (0-18 years old) with bacterial meningitis. Risk factors, signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments and case fatality rate were recorded., Results: During the period of the study, 1344 meningococcal meningitis were reported among 2951 (45.5%) bacterial meningitis. Mean age was 4.4 years (+/-4.7, median 2.5) and 2/3 cases occurred in children under 5 years (68.5%). Serogroup B (59.1%) was preponderant following by serogroup C (28.9%). 25% of children had received an antibiotic treatment 24hours before lumbar puncture. A shock was reported in 31.3% of cases. Cerebrospinal fluid culture was positive in 73% of cases. All N. meningitidis isolates were susceptible to cefotaxime and ceftriaxone while 41.6% and 25.7% showed reduced susceptibility to penicillin and amoxicillin respectively. Two cases of meningitis due to isolates of serogroups C and B were reported in two children that were respectively vaccinated using A+C plain saccharide vaccine or two doses of MenBvac vaccine. All patients had received beta-lactamin. Global case fatality rate was 6.6% but was higher (9.9%) for serogroup C than for serogroup B (5.5%) (p=0,007)., Conclusion: This study is among the largest series of microbiologically documented meningococcal meningitis to date (more than 1300 cases). In France, meningococal is responsible for 50 % of meningitis. Effective meningococcal serogroup B vaccine and serogroup C vaccination recommendation could lessen considerably the burden of meningococal meningitis.

Objectives: Consequence of the introduction of vaccines against bacteria involved in meningitis in children and various recommendations concerning antibiotics, the epidemiology of bacterial meningitis has changed during the last fifteen years. The GPIP/ACTIV (Groupe de Pathologie Infectieuse Pédiatrique and Association Clinique et Thérapeutique Infantile du Val de Marne) set up an active surveillance network to analyze the clinical and biological features of bacterial meningitis., Methods: From 2001 to 2007, 252 French pediatric wards working with 168 microbiology laboratories enrolled all children (0-18 years old) with bacterial meningitis. Risk factors, vaccination status, signs and symptoms, cerebrospinal fluid analysis, treatments and case fatality rate were recorded., Results: 2951 cases of bacterial menigitis were recorded by 237 pediatric wards. Geographical distribution covered a large part of the national territory. Overall, the annual number of cases varied from 452 (in 2001 and 2003) to 378 (in 2004). Meningococcal and pneumococcal meningitis respectively represented about the half (46 %) and the third (28 %) of cases. Few cases of Haemophilus influenzae meningitis were reported (3 %). For the neonatal period, group B Streptococcus and E. coli were the most frequently identified pathogens. In children less than one year old, pneumococcus was the first one, and after 1 year, meningococcus was predominant. The mortality rate varied according to bacteria, 6.6 % for the meningococcus, 11.6 % for pneumococcus, 14.1 % for group B streptococcus and 16.7 % for Listeria meningitis. It varied also with age, 14.9 % among infants 1 to 2 months old and 6.3 % in children over 5 years., Conclusion: Closed to 3000 meningitis were recorded during seven years in children, which underlines the interest of the survey. This network is principally supported by the goodwill and availability of pediatricians and microbiologists who participate in the study. This special supplement issue of Archive de Pédiatrie allows a complete presentation of our results. In next following years, any amendment to the immunization schedule, any perspective of implementation of new vaccines will transform the epidemiology and clinical caracteristics of bacterial menigitis. Therefore, continued surveillance appears necessary.

Background: Pneumococcal meningitis represents one major cause of morbidity and mortality in children in France. The GPIP/ACTIV (Groupe de Pathologie Infectieuse Pédiatrique and Association Clinique et Thérapeutique Infantile du Val de Marne) set up an active surveillance network to analyze the clinical and biological features of pneumococcal meningitis and the impact of 7-valent pneumococcal conjugate vaccine (PCV7)., Methods: From 2001 to 2007, 252 French pediatric wards working with 168 microbiology laboratories enrolled all children (0-18 years old) with bacterial meningitis. Risk factors, signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments and case fatality rate were recorded., Results: Within the 7 years study period, 832 pneumococcal meningitis were reported among 2951 bacterial meningitis. In 2001 as in 2007, excluding the neonatal period, pneumococal meningitis represented nearly 1/3 of bacterial meningitis without significant decline in the number of reported cases (less than 30% for children under 2 years old). The peak of incidence was at 5 months of age and 61.7% of cases occured in children 2 to 24 months old. PCV7 vaccinated patients represented 154 cases from 2003 to 2007. In the vaccinated population, serotypes were identified in 136 cases. Few vaccine serotypes (VT) were identified (n=18). The most important was serotype 19F (n=8) followed by 6B (n=4) and 14 (n=3). Three vaccine failures (case occurring after complete vaccination) were observed (serotypes 6B, 4 and 19F). Remaining cases (n=118) were mainly due to non vaccine serotypes (NVT): serotypes 19A, 15B/C and 7F. In 2007, the serotype 19A, more often intermediary strains to cytoxin, represented about 20% of cases. Among non vaccinated children, VT decreased between 2001 and 2007 (59/92 in 2001 vs 15/39 in 2007). Case fatality rate was stable around 11.4%., Conclusion: In France, probably because of the insufficient vaccination coverage and the slow implementation of the PCV7, the expected decline in the number of cases of pneumococcal meningitis has not been observed. The impact of PCV7 appeared clearly since only few cases of VT pneumococcal meningitis were reported in vaccinated children.

Objective: Delayed cerebrospinal fluid sterilization is defined by a positive second lumbar puncture, recommanded according to the guidelines from the French Consensus Conference of 1996 between the 36th and 48th hours after the beginning of antibiotics prescribed for pneumococcal meningitis. The aim of this study was to analyze specifically delayed cerebrospinal fluid sterilization, identified during the first 5 years of the French observatory of children bacterial meningitis., Patients and Methods: The Groupe de Pathologie Infectieuse Pédiatrique (GPIP) and Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV) has set up since the first of January 2001 a descriptive national multicenter network, to determine incidence, main characteristics, and prognosis of bacterial meningitis in children. A questionnaire, available in all paediatric unit taking care of bacterial meningitis, was completed by a referral doctor. It contained reasons for inclusion in the study, anamnesis, clinical examination, treatment, pneumococcal characteristics, and short term prognosis. Delayed cerebrospinal fluid sterilization were identified, and the analysis of their medical records completed the questionnaire., Results: From 1st January 2001 to 31 December 2005, 616 pneumococcal meningitis were identified. Among them, 442 had a second lumbar puncture, and 8 had delayed cerebrospinal fluid sterilization. The analyis of their medical records were reviewed to describe their characteristics. Two had an osteomeningeal breach, one a ventriculoperitoneal valve. All received previously an antibiotic, and were treated with a curative antibiotic by cephalosporins. Vancomycin was given in 6 cases. The antibiotic was inadapted to the French guidelines for 1 patient. There are 4 vaccine type pneumococci and only 1 strain was resistant to penicillin, and intermediate to cephalosporins. The controlled lumbar puncture was made between 36.5 and 179.4hours after beginning antibiotics. One patient has received a double dose of steroids. Three were in a coma, had convulsions, and were ventilated, none died. One patient has a sequellar paired deafness, two a severe disability, four a normal psychomotor development., Conclusion: The delay of sterilization is a rare situation and represented only 1.8 % of pneumococcal meningitis during the first five years of the observatory. These results suggest that a second lumbar puncture to assess sterilization could be proposed only in cases of unfavourable clinical course, MIC greater than or equal 0.5mg/l to 3GC, risk factors for delayed cerebrospinal fluid sterilization and high bacterial inoculum.

Clinical features and molecular characterization of 109 group B streptococci causing neonatal invasive infections were determined over an 18-month period in France. Sixty-four percent of the strains were from late-onset infections, and 75% were capsular type III. The hypervirulent clone ST-17 was recovered in 80% of meningitis cases.

The French Pediatric Infectious Diseases Group set up an active surveillance network to analyze the clinical and biological features of pneumococcal meningitis and the impact of the seven-valent pneumococcal conjugate vaccine (PCV7). From 2001 to 2005, 234 pediatric wards working with 166 microbiology laboratories enrolled all children with pneumococcal meningitis. Risk factors, signs and symptoms, vaccination status, cerebrospinal fluid analysis, treatments and case fatality rates were recorded. One hundred and sixty-nine centers (169/234) reported 616 cases, median age was 0.9 years and 67.2% of children were < or =2 years old. Underlying conditions were present in 13.1% of cases. The proportion of penicillin non-susceptible strains was 48.7%. Vancomycin plus a third-generation cephalosporin was prescribed in 92.7% of cases, and steroids were given before antibiotic treatment in 16.5% of cases. The case fatality rate was 10.8% overall and was not related to age, antibiotic susceptibility or steroid use. In children 2 to 24 months old compared to the prevaccinal period (2001-2002) a decrease of 28.4% of the number of cases was observed in 2005 (P < 0.05). Among children 2 to 24 months old, the proportion of serotypes covered by the PCV7 fell from 39/57 (68.4%) in 2001-2002 to 19/45 (42.2%) in 2005, while the proportion of non-vaccine serotypes and related serotypes increased respectively from 9/57 (15.8%) and 9/57 (15.8%) in 2001-2002 to 14/45 (31.1%) and 12/45 (26.7%) in 2005. Among 52 cases of pneumococcal meningitis that have occurred in vaccinated children (> or =1 dose) with PCV7, 7 were due by vaccine serotypes. This study provides data on underlying conditions, penicillin susceptibility, serotype evolution according to vaccination status and risk factors for mortality for pneumococcal meningitis in children from 2001-2005 in France.