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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 those15 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.

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.Over a 12-year period, 233 pediatric wards working with 168 microbiology departments throughout France were asked to report all cases of bacterial meningitis.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 (MIC0.5 μg/mL) represented less than 3% of cases, with no identified resistant strain since 2010 (MIC2 μg/mL). Between 2001 (n=67) and 2012 (n=9), the number of NmC meningitis cases decreased by 87%.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.

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.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.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%, P0.001). 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%, P0.0001). This trend was also observed for H. influenzae carriage (49% versus 18.7%, P0.0001). Multivariate analysis in the healthy group showed that siblings and day care center (or school) increased the carriage of S. pneumoniae and H. influenzae.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.

Acute bacterial parotitis is a rare infectious disease in infants under 3 months of age.To describe the clinical characteristics and the course of acute bacterial parotitis in infants less than 3 months old.Infants under 3 months of age, hospitalized at Robert Debré university hospital, Paris, France, between January 2005 and December 2009 for acute bacterial parotitis, were included in a retrospective study.Five infants less than 3 months of age were included in this study, for a frequency of 2.5/1000 hospitalizations in this age group. All were born at term, 4 of 5 were male. Three of the 5 patients had specific clinical signs of parotitis on admission. One patient had septic shock on admission. The ultrasound confirmed the parotitis in all cases. No parotid abscess was demonstrated on imaging. All patients had at least one abnormal inflammatory biological test (WBC, CRP, PCT). Bacteria were identified in 4 of 5 cases: Staphylococcus aureus was isolated in the pus culture of the Stenon duct in 2 patients and a group B Streptococcus was isolated from blood culture of 2 other patients. The duration of intravenous antibiotic therapy varied from 4 to 13 days, and the total duration of antibiotic therapy was between 10 and 16 days. No surgical procedures were needed.Acute bacterial parotitis in infants under 3 months of age might be associated with localized infections due to S. aureus, but also with a more severe clinical presentation due to group B streptococcus infection. Early diagnosis and appropriate antibiotic therapy might prevent the progression to serious complications.

The choice of antibiotics (ATB) to treat acute otitis media (AOM) has to take into account the level of resistance of bacteria species implicated. The aim of this study was to evaluate in France, ATB resistance of pneumococci and H. influenzae isolated from the nasopharyngeal flora, in children with AOM, vaccinated with 7 valent pneumococcal conjugate vaccine (PCV7).From 2006 to 2010, 66 pediatricians performed nasopharyngeal specimens of children 6 to 24 months with AOM. Demographic characteristics, history, vaccination status and symptoms were reported on a case report form transmitted to ACTIV.Of the 3,501 children included (mean age 13.5 ± 5 months), over 98% were PCV7 vaccinated and 41.1% were cared in day care center. A total of 47.3% of children had received ATB within 3 months before inclusion (cephalosporins, 22.6% and amoxicillin clavulanate, 19.2%). Pneumococcus and H. influenzae carriage was respectively 57.9% and 48.2%. Pneumococcal strains with reduced susceptibility to penicillin represented 46.3% of cases (3.9% highly resistant strains and 42.4% intermediate resistant strains). Factors that increased the risk of carrying these strains were: day care center (OR: 1.5, 95% CI: [1.2, 1.9]) and two courses or more of ATB before inclusion (OR: 2.6 (95% CI: [2.0, 3.4]). For H. influenzae strains the proportion of ßlactamases+ producing strains was 17.1% and those with reduced susceptibility due to penicillin binding protein changes (BLNAR+ strains+) accounted for 7.7% of cases. Three factors increased the risk of carriage BLNAR+ ßlactamase+ producing strains: age equal or greater than 12 months (OR: 3.5, 95% CI: [1.2, 10.3]), cephalosporin use (OR: 2.5, 95% CI: [1.0, 6.1]) and two courses or more of ATB before inclusion (OR: 3.1, 95% CI: [1.2, 8.0]).The data in this study (reduction of ßlactamase producing H. influenzae strains and increase of intermediate penicillin pneumococcal strains) should help to change the choice of antibiotics for AOM in children in France, by reducing the role of oral cephalosporins and secondly, by giving frontline amoxicillin ± clavulanic acid.

The healthy carrier of Streptococcus pneumoniae (S. pneumoniae) has been studied very little at the national level. With the emergence of antibiotic-resistant strains worldwide, and the emergence of new serotypes, an epidemiological survey is needed before the vaccine can be introduced in Morocco.This study's objective was to determine the prevalence and risk factors of pneumococcal nasopharyngeal carriage in children less than 2 years of age in the Marrakech region and to assess the antibiotic susceptibility of the isolates and the serotypes present prior to the introduction of the conjugate pneumococcal vaccine.From 2008 to 2009, 660 nasopharyngeal samples were collected on children under 2 years of age during scheduled visits to dispensaries for routine immunization in the Marrakech region.S. pneumoniae carriage was found in 45.8% of children. Of the 660 samples, 302 strains were isolated. The percentage of pneumococcal strains with reduced susceptibility to penicillin (PRSP) was 34.7%. Among these strains, 87.1% showed low-level resistance and 12.9% high-level resistance. Resistance to amoxicillin was found in 3.3% of the strains and no strains were resistant to cefotaxime. Several risk factors for pneumococcal carriage were identified, the main ones being breastfeeding less than 2 months, the presence of more than one sibling, passive smoking, and low socioeconomic level. The most frequent serotypes were 19F, 6, 14, 23, 18, and 9. The study of the vaccine serotype distribution showed that the theoretical vaccine coverage of the 7 valent vaccines was at 57% for all the isolates.These data show the frequency and the risk factors on nasopharyngeal carriage, and report the status of penicillin resistance of strains carrying children less than 2 years of age in the Marrakech region. The fluctuation of circulating serotypes at the national level underscores the importance of epidemiological surveillance carried out before the introduction of the heptavalent vaccine in Morocco.

Listeriosis is a serious invasive disease which affects mainly pregnant women, newborns and immunocompromised adults.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 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.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).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.

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.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.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 %).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.

To conduct a descriptive analysis of clinical, biological and prognostic aspects of Escherichia coli meningitis in young infants.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.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%, p10(-4)) and neurological failure (76% vs 19%, p10(-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, p10(-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 (p0.001).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.

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.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.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.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.

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).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.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.

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).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.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%.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.

In this study, the authors report the distribution of serogroups/serotypes and their susceptibility profiles of Streptococcus pneumoniae causing recurrent and difficulties to treat acute otitis media (AOM) in children obtained at the ENT outpatient clinic of Robert Debré Hospital in Paris, between 2002-2008 after the implementation of the 7-valent pneumococcal conjugate vaccine. In this retrospective study, 126 S. pneumoniae isolates were obtained by tympanocentesis from 126 children with AOM during three different periods: 2002-2003 (period 1), 2004-2005 (period 2), and 2006-2008 (period 3). In period 1, the most common serotype was 19F. Between period 1 and period 3, the proportion of serotype 19F decreased from 39 to 13% (P=0.03). In contrast, the proportion of serotype 19A increased from 25 to 60% (P=0.03). So, they observed that vaccine-related serotype 19A became dominant among young children with AOM in 2006-2008. Overall, 15.1% of the isolates were penicillin susceptible, 73.8% intermediate and 11.1% were resistant. Most (94%) of the S. pneumoniae serotype 19A were penicillin intermediate.

The diagnosis of acute osteomyelitis and septic arthritis is a clinical one. Acute-phase reactants, such as white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are useful to help the clinicians at the time of initial diagnosis. The WBC count may be normal in up to 80 % of cases and it is not a reliable indicator. The ESR is elevated in 80 % of cases. CRP is elevated more than 80 % of cases. CRP rises rapidly within 48 hours of admission and returns to normal within a week after appropriate therapy. Its rapid kinetics is useful for follow-up of the response treatment. Patients who require surgical drainage procedures have prolonged time to normalization of CRP. PCT is a useful specific marker for predicting severe infection but its sensibility to detect bone and joint infections seems to be low.

Streptococcus pneumoniae (Sp) is an important cause of morbidity and mortality among paediatric infectious diseases. The aim of this study is to analyse specific data on Sp meningitis out of the Bacterial Meningitis (BM) French Surveillance Network about mean age of BM cases and clinical features. Overall 367 Sp BM were reported between January 2001 to January 2004 (sex ratio M/F: 1.3), 69.7% were2 years old, median age 0.8 year (minmax 0-16.8 years). Before two years old children, 94.1% had no medical risk factor and no underlying conditions: on the other hand, after two years old, these factors were reported in 27% cases (P0.001). Mortality rate was 10.9%. On account of a Sp BM's pic at five months, data of the BM French Surveillance Network confirm the necessity of an early vaccination. The vaccine administration at two, three, four months with a booster during the second year, recommended in the vaccinal french calendar, seems particularly adapted to the Sp BM in France.

To review the bacteriological features and treatment of suppurative cervical lymphadenitis in children in order to achieve optimal treatment.Forty-five children were hospitalized. Time of hospitalization was evenly distributed over Year and between Years. Age ranged from 2.5 Months to 13.5 Years (median 1 Year 10 Months). Twenty-nine patients had received prior antibiotic treatment. Bacteriological samples were sterile in 15 out of 45 children and were positive for Staphylococcus (all meti-S) in 20. Cefotoxim and fosfomycin were prescribed and was sufficient in 14 children (with needle aspiration). Surgical drainage was performed in the other cases.Staphylococcus aureus is the predominant causal agent for acute suppurative lymphadenitis in children. Antibiotic therapy in the outpatient setting does not always prevent abscess formation and surgical drainage may be required.

Recurrent respiratory tract infections are a common reason for visits to primary care practitioners or hospital physicians. They are placed at the junction of several medical specialities: paediatrics, ENT, pneumology, allergology, immunology, infectiology. The great diversity of the laboratory tests requested and on the other hand the proposed treatments, are the consequences of the diversity of the patients encountered and the paucity of the evidence based-medicine studies in this setting. The dilemma is how to identify the child for which recurrent respiratory tract infections are the witness of underlying condition, without performing repeated medical examinations, laboratory tests and treatments for normal children for which immunologic development occurs normally. The essential tools are the history analysis, physical examination and few laboratory tests. The other questions are how to include, for these patients, influenza and pneumococcal vaccines in the immunization program and how to assess the benefit/risk ratio and the cost of surgical treatments. This paper presents the thought of an expert group trying to define the situations where biological tests or treatments are useful.

Meningococcal disease due to Neisseria meningitidis of serogroup W135 (N. meningitidis W135) is increasing in France. Clinical and outcome data concerning these infections in children are scarce. We report five cases of children hospitalized between June 2000 and December 2002 for N. meningitidis W135 infection. Extra-meningeal septic and/or non-septic complications were frequent and a prolonged post meningococcal inflammatory syndrome was reported. In N. meningitidis W135 infections a careful clinical evaluation of potential extra-meningeal complications and a long term follow up of children are needed.

Streptococcus pneumoniae is the most common bacterial cause of invasive and non-invasive infections in children of less than two years. The high level of resistance to penicillin and other antimicrobial agents observed particularly in France is responsible of the difficulties concerning the treatment of acute otitis media and meningitis due to S. pneumoniae. Potential positive consequences of the implementation of pneumococcal conjugate vaccine may include prevention of invasive diseases and prevention of spread of the drug resistant-strains.

Acute otitis media is the most common bacterial infection in the child under 5 years of age and the leading reason for antibiotic prescriptions in Western countries. The choice of optimal antibiotic treatment is based essentially on microbiologic epidemiologic studies. The bacteria most often responsible for otitis belong to the commensal flora of the nasopharynx. French studies using paracentesis show that the main bacteria responsible for acute otitis media are H. influenzae, S. pneumoniae and M. catarrhalis. The epidemiology of resistance to antibiotics has recently changed, with the appearance of pneumococcal strains having reduced sensitivity to penicillin, and which have played a major role in treatment failures.

Three surveys were successively carried out regarding aminoglycoside use: one analysis of amikacine prescriptions in the most prescribing clinical wards and two surveys among nurses and physicians respectively on prescribing, administering and monitoring aminoglycosides.On 43 amikacine prescriptions analyzed in a month, one daily dose infusion in 30 minutes was observed in most of the patients (70%), doses and indications matched most often the official license. Half of patients treated for more than five days had no drug level monitoring. Sample collection by nurses was very erratic making results obtained not interpretable.Subsequently, guidelines regarding aminoglycoside use were designed by the interest group, approved by the drug committee and sent to all hospital prescribers and nurses.

In this randomized open study, 325 children aged two to 15 years with acute tonsillitis and a positive test of GA beta H streptococcal antigen were treated with josamycin 50 mg.kg-1.day-1 b.i.d for 5 days, or penicillin 50,000 to 100,000 IU/day t.i.d for 10 days. Clinical assessments and throat cultures for GA beta HS isolation were performed at the inclusion visit (V1), at the end of treatment visit (V2: day 12 for all patients) and at the follow-up visit (V3: day 30). In case of positive GA beta HS culture, the bacterial DNA by RFLP was performed to differentiate between the persistence (presence of original strain at V2), relapse (eradication at V2 and acquisition of same strain at V3) and reinfection (eradication at V2 and acquisition of different strain at V3).Two hundred and twenty-three patients were included in the bacteriological and clinical criteria per protocol analysis. At V2, eradication rates were comparable: 82% in josamycin and 80% in penicillin patients; clinical cure rates were 90% and 89%. At V3, relapse of GAS assessed only on clinically and bacteriologically cured patients at V2 occurred in 12% of josamycin patients and 12.8% of penicillin patients. Tolerance was good; 14% and 10% of josamycin and penicillin patients respectively experienced an adverse event.In this non-inferiority study, the efficacy of a 5-day course of josamycin is comparable to reference treatment in GA beta HS tonsillitis in children.

The aim of this study was to analyze the epidemiological evolution of causal germs in meningitis in children aged 1 day to 15 years and determine the relationship between pretreatment concentrations of bacteria in cerebral spinal fluid (CSF), patient age, bacterial species and bacteriological eradication.A quantitative analysis of germs was performed in 212 children with bacterial meningitis (mean age 19.8 months).Bacterial counts ranged from 2.10(1) to 4.10(9) CFU/ml in CSF. Among the 212 patients, 52 (24.5%) had counts 10(7)/ml. Infants had significantly higher counts than the other age groups. Mean counts for Hoemophilus influenzoe serotype B were not different from those for Streptococcus pneumoniae but were significantly higher than for Neisseria meningitidis. Compared with initial germ counts, 98.5% of the CSF specimens were sterile at 24 and 48 hours and 100% at 72 hours.Germ counts were higher in infants.

Between April and October 1997, 21 children of 4 days to 13 years old were admitted to the Pedatric Unit of Aulnay Sous Bois's Hospital for viral meningitidis. The number of white blood cells in the cerebrospinal fluid (CSF) was between 1 and 612 cells/mm3, with, on an average, 56% of segmented cells, 34% lymphocytes and 34% monocytes. Proteins and glucose of CSF were standard. One CSF was normal. Viral meningitidis was confirmed by viral culture of CSF onto MRC5. Enterovirus were identified by direct immunofluorescence (Monoclonal Mouse Anti-Enterovirus, Dako). Serotyping (Enterovirus antisera, Eurobio, Trousses 4) identified an echovirus 30 in all cases. A highly conserved 154 bp sequence at the 5'non-coding region was studied by reverse transcription-polymerase chain reaction (RT-PCR) followed by single-strand conformation polymorphism (SSCP) (GenPhor, Pharmacia) analysis. Two dominant SSCP patterns were observed: the first contained 4/21 strains and the other 10/21 strains. The SSCP patterns of the 7 other strains were different. These results show that 2 echovirus 30 dominant clones were responsible of viral meningitidis admitted to the Pediatric Unit of Aulnay Sous Bois's hospital, between april and october 1997. The PCR-SSCP of the 5'non-coding region of echovirus 30 is a convenient, simple, reproducible epidemiologic method and it's easily applicable in a general hospital.

As many as 90% of all community-acquired urinary tract infections (UTIs) and more than 30% of nosocomially acquired UTIs are caused by E coli. The migration of bacteria into proximal urethra and bladder mucosa requires that the organisms travel "upstream" and resist being carried away by the flow of urine. Colonisation requires binding of specific adhesions of the bacteria to appropriate receptors on the surfaces of the epithelial cells. P fimbrae are found in 80%, 30% and 20% of strains from patients with pyelonephritis, cystitis and asymptomatic bacteriura, respectively. P fimbrae are found in only 30% of strains isolated from patients with pyelonephritis associated with compromising host factors such as vesicoureteral reflux, urinary tract anatomical abnormalities and recent urinary tract instrumentation.

PROBABILITY-BASED ANTIBIOTIC THERAPY: In children, the risk of an unfavorable course of bacterial infections requires careful selection of the initial antibiotic prescription based on the disease state, bacterial epidemiology and the child's age. ACUTE COMMUNITY ACQUIRED PNEUMONIA: Before the age of 5 years, antibiotics active against Haemophilus influenzae such as amoxicillin or clavulanic acid can be given orally. In children over 5, amoxicillin or a macrolide are effective. SEVERE EAR, NOSE AND THROAT INFECTIONS: For sore throats, clinical and bacterial results of a 4-day antibiotic regimen using a second generation cephalosporin are equivalent (with better compliance) to a 10-day regimen of penicillin V. For acute middle ear infections, a combination of amoxicillin-clavulanic acid is usually prescribed as initial treatment. COMMUNITY ACQUIRED BACTERIAL MENINGITIS: The most recent consensus established the indication for cefotaxime or ceftriaxone. The increasing number of peni-R pneumococci and the major drop in the frequency of Haemophilus infections have led to new therapeutic propositions currently under investigation. ACUTE SKIN INFECTIONS: For impetigo, general antibiotics-oxacillin or a derivative-are required due to the risk of contagion. BONE AND JOINT INFECTIONS: For these urgent situations, in vitro sensitivity and antibiotic penetration into the infected tissue are the determining factors. BACTERIAL DIARRHEA: Antibiotics are not required in case of acute diaarhea with little or no fever. Antibiotics could be discussed for cholera-like diarrhea and are required in case of invasive bacterial diarrhea, shigelosis, cholera, and Clostridium difficile as well as diarrhea with fever and blood loss in infants or salmonella-induced diarrhea with signs of extradigestive complications. URINARY TRACT INFECTIONS: The choice of the antibiotic and the duration of treatment depend on the clinical presentation: lower tract infection, acute pyeloephritis, or prophylaxis. The causal germ must be identified for adapted antibiotic treatment.

Careful epidemiological studies and sophisticated diagnostic procedures are necessary to prove that bacterial infection is nosocomial in origin. DNA finger printing method can be useful with this aim in view.A 11 month-old girl suffered from a febrile pneumonia. She developed acute meningitis 15 days later; culture of CSF grew Streptococcus pneumoniae, serotype 23 F, resistant to beta-lactamines, erythromycin and cotrimoxazole. She died 24 hours later. Five days after this death, a 5 month-old infant hospitalized in the next bed developed an acute pulmonary infection due to the same strain with the same bacterial characteristics; this patient was cured with cefotaxime plus vancomycin and gentamicin. Randomly amplified polymorphic DNA analysis showed an identical profile of both strains.This is the first case of meningitis due to penicillin-resistant Streptococcus pneumoniae (PRSP) associated with nosocomial spread between two children in adjacent beds. This case suggests that it is necessary to isolate patients with PRSP infection during hospitalization.

Third generation cephalosporin as cefotaxime or ceftriaxone is the best first line treatment. Duration of treatment is 7 to 10 days in uncomplicated disease. Dexamethasone used very early--before or at the same time of the antibiotic injection--seems to decrease sensorial sequelae. Amikacin by IV route, decreases short term complications. For bacterial meningitis due to intermediate penicillin pneumococci, an increase in daily dose of beta-lactamin is recommended; for resistant pneumococci, vancomycin by continuous infusion and with large doses is used. Chemoprophylaxis by rifampicine is effective for both Meningococcus and Haemophilus. Haemophilus influenzae b vaccination will decrease systemic infection due to this pathogen. In newborns, morbidity is higher, due in part to brain abscesses. Therapeutic choice is not the same for materno-foetal and postnatal infection. Antibiotherapy duration is, at least, 15 days and 21 days for gram-negative bacteria.

Epidemiological surveys which are not frequently carried out in medical practice should provide useful information for the choice of antibiotics to be prescribed in community-acquired infections particularly with the recent development of therapeutic difficulties due to resistant strains. We therefore analyzed the prevalent pharyngeal flora in a general patient population.The study was conducted during a single 24-hour period in 1991 by 43 general practitioners and included 645 subjects consulting for benign affections. No patient selection was made. Two pharyngeal swabs were obtained from each subject and cultured in aerobic and anaerobic conditions. Internationally accepted methods for identifying bacteria in pharyngeal samples all performed by one well-equipped laboratory. Beta-lactamase activity was determined with the nitrocephine technique, both directly and after culture.Patient age varied from 16 to 45 years; most (68.5%) consulted for reasons other than ear-nose-throat affections. Only 41 patients (4.3%) consulted for sore throat and 65.4% had not received antibiotics for at least 6 months. Haemophilus influenzae was found in 59.6% of the patients, 20% of the strains were beta-lactamase producers as were 83.7% of the Moraxella catarrhalis strains identified.These factors are indicators of potential risk of therapeutic failure when using beta-lactams unstable to beta-lactamases for the treatment of pharyngeal infections.

An epidemiological study was conducted in order to monitor the involvement of penicillin-resistant pneumococci (PRP) in treatment failure in acute otitis media (AOM), in an area of France where resistance to antibiotics is high. A total of 293 children presenting to 12 ear, nose and throat (ENT) specialists were included in the study. The mean age of the patients was 15.3 months and most of the children (58.7%) were attending day care centres. Bacteriological sampling demonstrated that in 146 cases (49.8%), no pathogen was present at the time of treatment failure. In the remaining patients Streptococcus pneumoniae was the most frequently recovered pathogen, being isolated from 81/147 (55.1%) of bacteriologically documented cases. Serotype 23F was the predominant strain, representing 53% of all S. pneumoniae isolates recovered. Resistance or reduced susceptibility to the prescribed antibiotic was seen in 70/81 (86.4%) of the S. pneumoniae isolates. In 32 out of 49 children administered a beta-lactam antibiotic, treatment failure involved PRP. Amoxycillin seemed to be the most active oral beta-lactam against these pathogens. The multiresistance of S. pneumoniae poses a serious therapeutic problem and should make myringotomy and bacteriological sampling obligatory in cases of antibiotic treatment failure.

Due to a worldwide increasing number of cephalosporin resistant Streptococcus (S) pneumoniae strains, it appears necessary to modify the current treatment of pneumococcal meningitis. The authors recommend an initial antimicrobial regimen associating cefotaxime or ceftriaxone to vancomycin in any case of bacterial meningitis in which S pneumoniae appears to be involved (Gram positive cocci on direct examination of the CSF and/or presence of soluble bacterial antigen). There is also a need for a reappraisal of the duration of the treatment which, in any case, should not be shorter than 10 days. In the case of meningitis due to a penicillin resistant S pneumoniae, lumbar puncture must be repeated until sterilisation of the CSF.

Nosocomial infection cause severe morbidity and mortality in pediatric patients. To find the cause of an infectious disease outbreak, epidemiologists need to determine early on whether a single strain of microorganism is responsible for the majority of cases. Phenotypic characteristics have been widely used in epidemiologic studies. However with most systems poor reproducibility, poor sensitivity have been reported and they do not reliably show enough strain-to-strain variation to be sufficiently discriminative. Molecular approaches like the analysis of the restriction fragment length polymorphism of the total DNA and of the rDNA regions and pulsed-field gel electrophoresis typing have now been applied with success to a large number of bacterial species associated with epidemics.

Moraxella catarrhalis is a Gram-negative diplococcus of the Neisseriaceae family now recognized as a cause of acute otitis media in pediatric patients and of lower respiratory tract infections in debilitated adults. The finding that 80% to 90% of strains produce beta-lactamases together with reports of cases of bacteremia and arthritis due to M. catarrhalis suggest an increasing pathogenic role for this organism. Antibiotic susceptibility testing suggests that the greatest bactericidal effect is provided by amoxicillin-clavulanic acid.

The minimum inhibitory concentrations (MICs) of vancomycin and teicoplanin were determined for 32 coagulase-negative staphylococci strains recovered from blood specimens from pediatric intensive care patients. All the strains were susceptible to vancomycin (MIC less than 4 mg/l). Sixteen strains were susceptible to teicoplanin (MIC less than 4 mg/l) and the sixteen remaining strains exhibited intermediate susceptibility, with MICs of 8 mg/l (10 strains) or 16 mg/l (6 strains). Inhibition zone diameters seen with vancomycin during agar diffusion susceptibility testing were consistently greater than 17 mm. Inhibition zones obtained with teicoplanin were 17 mm or more in diameter for 30 strains and under 17 mm in diameter for 2 strains. For 14 strains (44%), agar diffusion testing failed to detect the decreased susceptibility to teicoplanin revealed by MIC determinations. The agar diffusion method does not seem reliable for the determination of in vitro susceptibility to teicoplanin.

A differential quantitative study of the fecal flora was used to appreciated the intestinal bacterial flora of 41 hospitalized children, with no infection and receiving no antibiotic treatment. Thus, it was possible to establish the bacterial normal profile of intestinal of hospitalized child. Because of the stability of the fecal flora in those controls, it was possible to study the effect of colistin on the intestinal ecosystem, in 21 children. Colistin per os, with intestinal nutrition and colistin IM in combination with gentamicin IM did not have any quantitative or qualitative effect on fecal flora. Colistin per os, with exclusive parenteral nutrition caused by disappearance of sensitive strains and their replacement by resistant organisms; this was followed by secondary septicaemia. This fact being a very high infectious risk, it leads us to abstain from administering colistin per os, when the intestine does not receive any food.

355 children, 3 months to 15 years old, presenting with acute otitis media, underwent a bacteriological study of otitis exsudate. From November 1985 to September 1987, 162 myringotomy and 149 acute otitis media spontaneously discharging were studied in Paris. From October 1981 to September 1987, 62 myringotomy and 46 spontaneously discharging acute otitis were studied in Valognes. There was none pathogenic bacterium in respectively 20 and 14% of the samples. Two or more pathogenic bacterium were isolated in 24 and 7% of the samples. In Paris as in Valognes, 3 pathogens were predominants: Haemophilus (17% were beta-lactamase producers), S. pneumoniae and Staphylococcus. There was only 5 and 3% Streptococcus pyogenes, 2% Branhamella catarrhalis in Paris, none in Valognes. Pseudomonas was present only in case of spontaneous otorrhea, even if recent. For the moment, the combination of amoxicillin with clavulanic acid is not our first treatment in case of acute otitis media in children. Actually we prescribe amoxicillin alone, 50 to 100 mg/kg/day. If the child is allergic to beta lactamin, we give him the combination of trimethoprime and sulfamethoxazole.

Twenty-six children, aged from 15 days to 14 years, were treated with cefotaxime. 5 were suffering from septicaemia, 14 from respiratory tract infection and were ventilated (intensive care unit), 4 from urinary tract infection and 3 from otitis media complicated with renal failure (nephrology unit). The choice of cefotaxime treatment was based upon the bacterial activity. The daily dose was 50 to 100 mg/kg by the i.m. route, or by slow intravenous injection every 8 hours. In 17 patients, cefotaxime was combined with an aminoglycoside (gentamicin or amikacin). The results were evaluated on the basis of clinical, radiological and bacteriological criteria and, whenever possible, were correlated to the serum levels of antibiotic. The antibiotic was clinically effective in 25 out of 26 patients. The three deaths that occurred, were due to the nature of the initial disease. Tolerance was good in all the patients studied. The efficacy of cefotaxime correlated well with the favorable in vitro bacteriological results and with serum concentrations. Cefotaxime is well tolerated as shown in newborn babies. Cefotaxime is markedly different from previous cephalosporins, because of its high antibacterial activity on most Gram-negative bacilli.

Loperamide has recently been proposed in the management of infants with severe protracted diarrhea. The purpose of this study was to determine the effect of loperamide (0.5 mg/kg/d) on fecal flora in 19 cases of severe protracted diarrhea. Criteria analysed were: clinical tolerance (vomiting and abdominal distension) and efficacy (number of stools, transit time and Na/k in stools); complete identification and counts of aerobic and strict anaerobic bacteria in fresh stools before and 4 to 8 days after the beginning of loperamide. Parental and/or oral alimentation remained unchanged during the entire study. Clinical resolution of diarrhea was rapid (less than 24 h) in 9 of 14 patients. In 2 cases ileus was observed and resolved when loperamide was discontinued. Although important changes in specific fecal flora counts was noticed for streptococcus D and proteus as compared to 5 controls, no bacterial overgrowth appeared or was worsened during loperamide treatment.

Rapid bactericidal effect is essential for therapy of severe Staphylococcus aureus infections in children. The in vitro activity of clinically achievable levels of vancomycin and its combinations with gentamicin, amikacin and rifampin plus amikacin was studied with the time-kill curve method at 2.5, 4, 6, 24 and 48 hours against 20 strains of Staphylococcus aureus isolated from children with severe staphylococcal infection. Vancomycin alone exerted a bactericidal effect at 48 hours. However, with the combinations vancomycin plus gentamicin, vancomycin plus amikacin and vancomycin plus amikacin plus rifampin a bactericidal effect was respectively observed at 24, 6 and 4 hours. Most rapid killing was achieved with vancomycin plus rifampin plus amikacin. Thus this antibiotic combination seems the most appropriate for initial treatment of severe staphylococcal infections in children.

The effect of antibiotic therapy on the intestinal flora was studied qualitatively and quantitatively in 41 infants. The results have been compared with 27 normal children of the same age and background. Antibiotics were responsible for the suppression of sensitive strains and for their replacement by resistant organisms but above all to a rapid multiplication of the intestinal flora. Colistin and pristinamycin caused these changes when given orally. Ampicillin when given both orally and parenterally but Colistin and the aminoglycosides when given parenterally did not have any effect. Fourteen cases of secondary septicaemia due to resistant organisms were observed but other factors were also important, namely the young age of the patients and intestinal problems (stasis and diarrhoea).

Monitoring of serum aminoglycosides is useful in neonates to ensure therapeutic efficacy and avoid toxicity. The choice of a method must take in count several informations: sample size, versatility, sensitivity, specificity, precision, rapidity, equipment requirements and reagent cost. Many methods are now available: Microbiological assay, Radioimmunoassay (RIA) techniques, Radioenzymatic assay (REA), "High Pressure" liquid chromatography (HPLC), Fluorescent immunoassay, Enzyme-Multiplied Immunoassay (EMIT) and Fluorescent polarization Immunoassay (FPIA). Microbiological assay is inexpensive but has major disadvantages: lack of specificity, low precision, requires 24 to 48 hours, large sample size. EMIT and FPIA are rapid, sensitive, highly specific and particularly adapted to the pediatric use but reagent are expensive.