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RSV is an almost obligatory virus responsible for upper (rhinitis and otitis) and lower (bronchiolitis and asthma attack) respiratory infections in children under 5 years of age. Reinfections are frequent at all ages because immunity is only partial and does not last long. Young children under the age of 1 are the most affected. The majority of these children are healthy. Having a risk factor (premature birth, heart disease, bronchopulmonary dysplasia, but also passive smoking) increases the severity of RSV pathology. Very few children currently benefit from prevention by anti-RSV monoclonal antibodies. The annual cost of care, the various socio-economic costs are a public health reality in three care sectors: out-patient, pediatric emergencies, hospitalization. Subsequent consequences: repeated wheezing and asthma, should also be taken into consideration and integrated into public health decisions. Progress in recognizing this pathology is desirable: distribution of diagnostic tests in the city; providing parents with information.Le VRS est un virus quasi obligatoire responsable d’infections respiratoires hautes (rhinite et otite) et basses (bronchiolite et crise d’asthme) chez l’enfant de moins de 5 ans. Les réinfections sont fréquentes du fait d’une immunité partielle, peu durable, à tous les âges de la vie. Les jeunes enfants de moins de 1 an sont les plus touchés. La majorité de ces enfants sont bien portants. Avoir un facteur de risque (prématurité, cardiopathie, dysplasie bronchopulmonaire mais aussi tabagisme passif) majore la sévérité de la pathologie à VRS. Très peu d’enfants bénéficient actuellement d’une prévention par les anticorps monoclonaux anti-VRS. La charge annuelle en soins, les coûts socioéconomiques variés constituent une réalité de santé publique portant sur les trois secteurs de soins : ambulatoire, urgences pédiatriques, hospitalisation.Les conséquences ultérieures : répétition de wheezing, asthme, devraient aussi être pris en considération et intégrés dans les décisions de santé publique.Des progrès dans la reconnaissance de cette pathologie sont souhaitables : diffusion des tests diagnostiques en ville ; information aux parents.

International audience; SARS-CoV-2 diagnosis is a cornerstone for the management of coronavirus disease 2019 (COVID-19). Numerous studies have assessed saliva performance over nasopharyngeal sampling (NPS), but data in young children are still rare. We explored saliva performance for SARS-CoV-2 detection by RT-PCR according to the time interval from initial symptoms or patient serological status. We collected 509 NPS and saliva paired samples at initial diagnosis from 166 children under 12 years of age (including 57 children under 6), 106 between 12 and 17, and 237 adults. In children under 12, overall detection rate for SARS-CoV-2 was comparable in saliva and NPS, with an overall agreement of 89.8%. Saliva sensitivity was significantly lower than that of NPS (77.1% compared to 95.8%) in pre-school and school-age children but regained 96% when considering seronegative children only. This pattern was also observed to a lesser degree in adolescents but not in adults. Sensitivity of saliva was independent of symptoms, in contrary to NPS, whose sensitivity decreased significantly in asymptomatic subjects. Performance of saliva is excellent in children under 12 at early stages of infection. This reinforces saliva as a collection method for early and unbiased SARS-CoV-2 detection and a less invasive alternative for young children.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally milder than in adults, but a proportion of cases result in hyperinflammatory conditions often including myocarditis. Methods To better understand these cases, we applied a multiparametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. Plasma cytokine and chemokine levels and blood cellular composition were measured, alongside gene expression at the bulk and single-cell levels. Findings The most severe forms of multisystem inflammatory syndrome in children (MIS-C) related to SARS-CoV-2 that resulted in myocarditis were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomics analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis characterized by sustained nuclear factor κB (NF-κB) activity and tumor necrosis factor alpha (TNF-α) signaling and associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type I and type II interferons, hyperinflammation, and response to oxidative stress related to increased HIF-1α and Vascular endothelial growth factor (VEGF) signaling. Conclusions These results provide potential for a better understanding of disease pathophysiology. Funding Agence National de la Recherche (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01; Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010; Laboratoire d’Excellence ‘‘Milieu Intérieur,” grant ANR-10-LABX-69-01; ANR-flash Covid19 “AIROCovid” and “CoVarImm”), Institut National de la Santé et de la Recherche Médicale (INSERM), and the “URGENCE COVID-19” fundraising campaign of Institut Pasteur., Graphical abstract, Context and significance Children with SARS-CoV-2 infection were initially thought to have only mild COVID-19 symptoms. However, several weeks into the first wave of SARS-CoV-2 infections, there was a surge of a postacute pathology called multisystem inflammatory syndrome in children (MIS-C). The authors recruited a cohort of children with suspicion of SARS-CoV-2 infection and uncovered hyperinflammation, hypoxic conditions, exacerbation of TNF-α signaling via NF-κB, and absence of responses to type I and type II IFN secretion in the most severe forms of MIS-C with severe myocarditis. This work led the authors to identify in monocytes and validate in peripheral blood mononuclear cells a molecular signature of 25 genes that allows discrimination of the most severe forms of MIS-C with myocarditis., Multiparametric analysis identifies, in monocytes and dendritic cells, a molecular signature of the most severe forms of multisystem inflammatory syndrome in children caused by SARS-CoV-2 infection. Severe myocarditis is characterized by an excess of TNF-α signaling via NF-κB, hypoxic conditions, and hyperinflammation in the absence of type I and type II interferon responses.

Acute bronchiolitis is one of the most common health burdens in infants worldwide and leads to frequent hospitalisation, morbidity and mortality (1). Children have been relatively spared by the COVID-19 pandemic, but reports of multisystem inflammatory syndrome (2) and probable long-term COVID (3) effects in children have started to emerge. One major concern was whether the overlap of the pandemic and seasonal bronchiolitis would put substantial pressure on healthcare systems. Bronchiolitis has a predictable seasonal pattern, primarily in autumn and winter, and in France this is between October and February. The second COVID-19 wave in France led to a two-week night curfew from 17 October 2020, followed by a full lockdown on 30 October. However, day care centres and primary and secondary schools remained open.

Background Respiratory syncytial virus (RSV) is the main cause of infant and child hospitalizations. The study objective is to estimate the RSV-associated hospitalizations and economic burden in young children in France to inform future preventive strategies. Methods We conducted a retrospective analysis of RSV-associated hospitalizations data from the French Hospital database (PMSI-MCO) which covers the entire French population. All children aged Results On average 50,878 RSV-associated hospitalizations (range: 43,715 – 54,616) per season was reported in France, 69% among children Conclusion RSV is an important cause of child hospitalization in France. The burden on healthcare system is mainly driven by

SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κB activity, TNF-α signaling, associated with decreased gene expression of NF-κB inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology.

Summary Background The extent to which very young children contribute to the transmission of SARS-CoV-2 is unclear. We aimed to estimate the seroprevalence of antibodies against SARS-CoV-2 in daycare centres that remained open for key workers' children during a nationwide lockdown in France. Methods Children and staff who attended one of 22 daycare centres during a nationwide lockdown in France (between March 15 and May 9, 2020) were included in this cross-sectional, multicentre, seroprevalence study. Hospital staff not occupationally exposed to patients with COVID-19, or to children, were enrolled in a comparator group. The primary outcome was SARS-CoV-2 seroprevalence in children, daycare centre staff, and the comparator group. The presence of antibodies against SARS-CoV-2 in capillary whole blood was measured with a rapid chromatographic immunoassay. We computed raw prevalence as the percentage of individuals with a positive IgG or IgM test, and used Bayesian smoothing to account for imperfect sensitivity and specificity of the assay. This study is registered with ClinicalTrials.gov, NCT04413968. Findings Between June 4 and July 3, 2020, we enrolled 327 children (mean age 1·9 [SD 0·9] years; range 5 months to 4·4 years), 197 daycare centre staff (mean age 40 [12] years), and 164 adults in the comparator group (42 [12] years). Positive serological tests were observed for 14 children (raw seroprevalence 4·3%; 95% CI 2·6–7·1) and 14 daycare centre staff (7·7%; 4·2–11·6). After accounting for imperfect sensitivity and specificity of the assay, we estimated that 3·7% (95% credible interval [95% CrI] 1·3–6·8) of the children and 6·8% (3·2–11·5) of daycare centre staff had SARS-CoV-2 infection. The comparator group fared similarly to the daycare centre staff; nine participants had a positive serological test (raw seroprevalence 5·5%; 95% CI 2·9–10·1), leading to a seroprevalence of 5·0% (95% CrI 1·6–9·8) after accounting for assay characteristics. An exploratory analysis suggested that seropositive children were more likely than seronegative children to have been exposed to an adult household member with laboratory-confirmed COVID-19 (six [43%] of 14 vs 19 [6%] of 307; relative risk 7·1 [95% CI 2·2–22·4]). Interpretation According to serological test results, the proportion of young children in our sample with SARS-CoV-2 infection was low. Intrafamily transmission seemed more plausible than transmission within daycare centres. Further epidemiological studies are needed to confirm this exploratory hypothesis. Funding Assistance Publique—Hopitaux de Paris; Mairie de Paris, Conseil Departemental de Seine Saint Denis. Translations For the French translation of the abstract see Supplementary Materials section.

Background Children have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections. Aim We tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection. Methods We set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36). SARS-CoV-2 antibodies directed against the nucleoprotein (N) and S1 and S2 domains of the spike (S) proteins were monitored by an in-house luciferase immunoprecipitation system assay. We randomly selected 69 SARS-CoV-2-seropositive patients (including 15 with MIS) and 115 matched SARS-CoV-2-seronegative patients (controls (CTL)). We measured antibodies against SARS-CoV-2 and HCoV as evidence for prior corresponding infections and assessed if SARS-CoV-2 prevalence of infection and levels of antibody responses were shaped by prior seasonal coronavirus infections. Results Prevalence of HCoV infections were similar in HOS, MIS and CTL groups. Antibody levels against HCoV were not significantly different in the three groups and were not related to the level of SARS-CoV-2 antibodies in the HOS and MIS groups. SARS-CoV-2 antibody profiles were different between HOS and MIS children. Conclusion Prior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

International audience; Importance: Multisystem inflammatory syndrome in children (MIS-C) is the most severe pediatric disease associated with severe acute respiratory syndrome coronavirus 2 infection, potentially life-threatening, but the optimal therapeutic strategy remains unknown. Objective: To compare intravenous immunoglobulins (IVIG) plus methylprednisolone vs IVIG alone as initial therapy in MIS-C. Design, Setting, and Participants: Retrospective cohort study drawn from a national surveillance system with propensity score-matched analysis. All cases with suspected MIS-C were reported to the French National Public Health Agency. Confirmed MIS-C cases fulfilling the World Health Organization definition were included. The study started on April 1, 2020, and follow-up ended on January 6, 2021. Exposures: IVIG and methylprednisolone vs IVIG alone. Main Outcomes and Measures: The primary outcome was persistence of fever 2 days after the introduction of initial therapy or recrudescence of fever within 7 days, which defined treatment failure. Secondary outcomes included a second-line therapy, hemodynamic support, acute left ventricular dysfunction after first-line therapy, and length of stay in the pediatric intensive care unit. The primary analysis involved propensity score matching with a minimum caliper of 0.1. Results: Among 181 children with suspected MIS-C, 111 fulfilled the World Health Organization definition (58 females [52%]; median age, 8.6 years [interquartile range, 4.7 to 12.1]). Five children did not receive either treatment. Overall, 3 of 34 children (9%) in the IVIG and methylprednisolone group and 37 of 72 (51%) in the IVIG alone group did not respond to treatment. Treatment with IVIG and methylprednisolone vs IVIG alone was associated with lower risk of treatment failure (absolute risk difference, -0.28 [95% CI, -0.48 to -0.08]; odds ratio [OR], 0.25 [95% CI, 0.09 to 0.70]; P =.008). IVIG and methylprednisolone therapy vs IVIG alone was also significantly associated with lower risk of use of second-line therapy (absolute risk difference, -0.22 [95% CI, -0.40 to -0.04]; OR, 0.19 [95% CI, 0.06 to 0.61]; P =.004), hemodynamic support (absolute risk difference, -0.17 [95% CI, -0.34 to -0.004]; OR, 0.21 [95% CI, 0.06 to 0.76]), acute left ventricular dysfunction occurring after initial therapy (absolute risk difference, -0.18 [95% CI, -0.35 to -0.01]; OR, 0.20 [95% CI, 0.06 to 0.66]), and duration of stay in the pediatric intensive care unit (median, 4 vs 6 days; difference in days, -2.4 [95% CI, -4.0 to -0.7]). Conclusions and Relevance: Among children with MIS-C, treatment with IVIG and methylprednisolone vs IVIG alone was associated with a more favorable fever course. Study interpretation is limited by the observational design..

BACKGROUND: Initial reports on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in children suggested that very young age and comorbidities may increase risk of severe evolution, but these findings remained to be confirmed. We aimed to analyze the clinical spectrum of hospitalized pediatric SARS-CoV-2 infection and predictors of severe disease evolution. METHODS: We conducted a French national prospective surveillance of children hospitalized with SARS-CoV-2 infection. We included all children with confirmed SARS-CoV-2 infection in 60 hospitals during February 15 to June 1, 2020. The main outcome was the proportion of children with severe disease, defined by hemodynamic or ventilatory (invasive or not) support requirement. RESULTS: We included 397 hospitalized children with SARS-CoV-2 infection. We identified several clinical patterns, ranging from paucisymptomatic children, admitted for surveillance, to lower respiratory tract infection or multisystem inflammatory syndrome in children. Children CONCLUSIONS: In contrast with preliminary reports, young age was not an independent factor associated with severe SARS-CoV-2 infection, and children

Acute arthritis is a common cause of consultation in pediatric emergency wards. Arthritis can be caused by juvenile idiopathic arthritis (JIA), septic (SA) or remain undetermined (UA). In young children, SA is mainly caused by Kingella kingae (KK), a hard to grow bacteria leading generally to a mild clinical and biological form of SA. An early accurate diagnosis between KK-SA and early-onset JIA is essential to provide appropriate treatment and follow-up. The aim of this work was to compare clinical and biological characteristics, length of hospital stays, duration of intravenous (IV) antibiotics exposure and use of invasive surgical management of patients under 6 years of age hospitalized for acute monoarthritis with a final diagnosis of JIA, SA or UA. We retrospectively analyzed data from 9/L [10–13.6]) when compared to SA (13.2 × 109/L [11–16.6]), p = 0.01. In synovial fluid leucocytes were higher in SA 105.5 × 103 cells/mm3 [46–211] compared to JIA and UA (42 × 103 cells/mm3 [6.4–59.2] and 7.29 × 103 cells/mm3 [2.1–72] respectively), p Kingellakingae in these patients.

SARS-CoV-2 infection in children is generally milder than in adults, yet a proportion of cases result in hyperinflammatory conditions often including myocarditis. To better understand these cases, we applied a multi-parametric approach to the study of blood cells of 56 children hospitalized with suspicion of SARS-CoV-2 infection. The most severe forms of MIS-C (multisystem inflammatory syndrome in children related to SARS-CoV-2), that resulted in myocarditis, were characterized by elevated levels of pro-angiogenesis cytokines and several chemokines. Single-cell transcriptomic analyses identified a unique monocyte/dendritic cell gene signature that correlated with the occurrence of severe myocarditis, characterized by sustained NF-κ B activity, TNF-α signaling, associated with decreased gene expression of NF-κ B inhibitors. We also found a weak response to type-I and type-II interferons, hyperinflammation and response to oxidative stress related to increased HIF-1α and VEGF signaling. These results provide potential for a better understanding of disease pathophysiology. Funding: The study was supported by the Institut National de la Sante et de la Recherche Medicale (INSERM), by the “URGENCE COVID-19” fundraising campaign of Institut Pasteur, by the Atip-Avenir, Emergence ville de Paris program and fond de dotation Janssen Horizon and by government grants managed by the Agence National de la Recherche as part of the “Investment for the Future” program (Institut Hospitalo-Universitaire Imagine, grant ANR-10-IAHU-01, Recherche Hospitalo-Universitaire, grant ANR-18-RHUS-0010, Laboratoire d’Excellence ‘‘Milieu Interieur”, grant ANR-10-LABX-69-01), the Centre de Reference Deficits Immunitaires Hereditaires (CEREDIH), the Agence National de la Recherche (ANR-flash Covid19 “AIROCovid” to FRL and “CoVarImm” to DD and JDS), and by the FASTFoundation (French Friends of Sheba Tel Hashomer Hospital). The LabTech Single-Cell@Imagine is supported by the Paris Region and the “Investissements d’avenir” program through the 2019 ATF funding – Sesame Filieres PIA (Grant N°3877871).CdC is the recipient of a CIFRE-PhD (Sanofi). L.B. was a recipient of an Imagine institute PhD international program supported by the Fondation Bettencourt Schueller. L.B. was also supported by the EUR G.E.N.E. (reference #ANR-17-EURE-0013) and is part of the Universite de Paris IdEx #ANR-18-IDEX-0001 funded by the French Government through its“Investments for the Future” program. S.M. was a recipient of an INSERM and Institut Imagine post-doctorat program supported by the Fondation pour la Recherche Medicale (FRMN°SPF20170938825). NS was a recipient of the Pasteur-Roux-Cantarini Fellowship. VGP obtained an Imagine international PhD fellowship program supported by the Fondation Bettencourt Schueller. BPP is the recipient of an ANRS post-doctoral fellowship. Conflict of Interest: DD, FRL, JT and MMM are listed as inventors on a patent application related to this technology (European Patent Application no. EP21305197, entitled “Methods of predicting multisystem inflammatory syndrome (MIS-C) with severe myocarditis in subjects suffering from a SARS-CoV-2 infection”). Ethical Approval: The study was approved by the Ethics Committee (Comite de Protection des Personnes Ouest IV, n° DC-2017-2987).

International audience; Aim: This study determined the influence of the COVID-19 pandemic on the occurrence of multisystem inflammatory syndrome in children (MIS-C) and compared the main characteristics of MIS-C and Kawasaki disease (KD).Methods: We included patients aged up to 18 years of age who were diagnosed with MIS-C or KD in a paediatric university hospital in Paris from 1 January 2018 to 15 July 2020. Clinical, laboratory and imaging characteristics were compared, and new French COVID-19 cases were correlated with MIS-C cases in our hospital.Results: There were seven children with MIS-C, from 6 months to 12 years of age, who were all positive for the virus that causes COVID-19, and 40 virus-negative children with KD. Their respective characteristics were as follows: under 5 years of age (14.3% vs. 85.0%), paediatric intensive care unit admission (100% vs. 10.0%), abdominal pain (71.4% vs. 12.5%), myocardial dysfunction (85.7% vs. 5.0%), shock syndrome (85.7% vs. 2.5%) and mean and standard deviation C-reactive protein (339 ± 131 vs. 153 ± 87). There was a strong lagged correlation between the rise and fall in MIS-C patients and COVID-19 cases.Conclusion: The rise and fall of COVID-19 first wave mirrored the MIS-C cases. There were important differences between MIS-C and KD.

BackgroundChildren have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS).MethodsThis cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup).FindingsSARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55·6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66·9 −100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection.InterpretationPrior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection.Evidence before this studyChildren seem to be less likely affected by SARS-CoV-2 infection and clinical course of COVID-19 is less severe than in adults. As those asymptomatic or mildly symptomatic children are underdiagnosed and their viral loads are comparable to those of adults, they may act as an asymptomatic reservoir for the spread of the virus. One explanation of the difference between the adult and the pediatric infectious profile might be that infection with seasonal human coronaviruses, which is very frequent from a very young age, could lead to cross protective immunity. We searched in PubMed, MedRxiv and BioRxiv for publications from inception to June 15, 2020, using the terms “COVID-19, SARS-CoV-2, children, serology, Kawasaki, Corona Virus”.Added value of this studySARS-CoV-2 mean prevalence rate was 11.7% from April 1 to June 1 and neutralizing antibodies were found in 55% of the tested seropositive children. Among patients with a Multisystem Inflammatory Syndrome, Kawasaki-like disease, 70% were SARS-CoV-2 seropositive and had neutralizing antibodies. COVID-19 and MIS attack rates, and anti-SARS-CoV-2 antibodies titres were not significantly impacted by prior seasonal coronavirus infection.Implications of all the available evidencePrior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children As antibodies against seasonal coronaviruses are very frequent and as these viruses circulate efficiently in human populations every winter, our results question to what extent the concept of herd immunity based on circulating antibodies can be applied to seasonal coronaviruses and possibly SARS-CoV-2.

This case series examines cardiac MRI findings in four children and adolescents admitted to intensive care in April 2020 for multisystem inflammatory syndrome and Kawasaki disease-like features related to coronavirus disease 2019 (COVID-19). Acute myocarditis occurred less than 1 week after onset of fever and gastrointestinal symptoms. Physical examination showed rash and cheilitis or conjunctivitis. All patients recovered after intravenous immunoglobulin therapy. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction was negative in nasopharyngeal, stool, and respiratory samples and was positive on serology. Cardiac MRI showed diffuse myocardial edema on T2 short tau inversion-recovery sequences and native T1 mapping, with no evidence of late gadolinium enhancement suggestive of replacement fibrosis or focal necrosis. These findings favor postinfectious myocarditis in children and adolescents with COVID-19.

International audience; The objective of this study was to determine the number of cases of pediatric meningitis or purpura fulminans associated with an incorrect vaccination status from 2011 to 2013 in France. A total of 48 children with vaccine-preventable meningitis or purpura fulminans, including three deaths, had an incorrect vaccination status: 26 cases were due to Neisseria meningitidis group C (54.2%), 19 to Streptococcus pneumoniae (39.6%), and three to Haemophilus influenzae type b (6.3%). The majority of patients (n = 35, 72.9%) had received no injection of the vaccine concerned. Over a 3-year period, 48 cases of bacterial meningitis or purpura fulminans in children could have been avoided if the French immunization schedule had been followed.

Successive implementation of seven-valent then 13-valent pneumococcal conjugate vaccines (PCVs) led to a marked decrease in pneumococcal disease burden, including pneumococcal meningitis. We assessed the long-term effect of implementation of PCVs on incidence of pneumococcal meningitis in children in France over a 16-year period.We did a quasi-experimental, population-based interrupted time-series analysis with a nationwide prospective survey over 16 years in France, recruiting children aged younger than 15 years from 227 paediatric wards from January, 2001, to December, 2016. The main outcome by the time-series model was the estimated incidence of pneumococcal meningitis per 100 000 children (of a population of 12·6 million children in 2017) before and after PCV7 and PCV13 implementation. The time-series model was based on segmented regression with autoregressive error.We enrolled 1778 children with pneumococcal meningitis. PCV13 implementation led to a significant reduction in monthly incidence of pneumococcal meningitis from 0·12 per 100 000 children before PCV13 to a nadir of 0·07 in December, 2014 (-38%, 95% CI -56·1 to -20·4; p0·0001). A sharp increase occurred during 2015 and 2016, (+2·3% per month, incidence of 0·13 per 100 000 children at the end of the study period, p=0·0002), mainly related to an increase of serotype 24F, which was frequently penicillin resistant.The early effect of PCV13 implementation greatly reduced the incidence of pneumococcal meningitis in children less than 15 years old. However, a sharp rebound in incidence linked to the emergence of serotype 24F compromised the long-term PCV efficacy. If confirmed in future studies and in other countries, pneumococcal meningitis incidence rebound and 24F emergence should be considered when developing next-generation PCVs.The French Pediatric Infectious Diseases Group, Association Clinique et Thérapeutique Infantile du Val de Marne, Pfizer, and for the National Reference Centre for Pneumococci, the French National Health Agency.

Acute hematogenous bone and joint infections (osteomyelitis, septic arthritis, osteoarthritis, and spondylodiscitis) affect more frequently children younger than 5 years of age. Early diagnosis and prompt treatment are needed to limit the risk of complications. Children with suspected bone and joint infections (BJI) should be hospitalized at the beginning of treatment. Surgical drainage is indicated in patients with septic arthritis and in those with periosteal abscess. Staphylococcus aureus is involved in BJIs in children at all ages; Kingella kingae is a very common causative pathogen in children under 4 years of age. The French Pediatric Infectious Disease Group recommends in children > 3 months of age empirical antibiotic therapy with appropriate coverage against methicillin-sensitive S. aureus with high doses (150mg/kg/day) of intravenous amoxicillin-clavulanate, cefuroxime or cefazoline. In most children with uncomplicated BJI, short intravenous antibiotic therapy for 3 days can be followed by oral therapy. The minimum total duration of antibiotic therapy should be 10 days for septic arthritis and 3 weeks for osteomyelitis.

This review focuses on the treatment of urinary tract infections (UTI) in children and in particular its recent changes. Areas covered: Acute pyelonephritis, acute cystitis and asymptomatic bacteriuria or asymptomatic infections have to be clearly distinguished. Prompt treatment is required in pyelonephritis and cystitis, but not in asymptomatic bacteriuria or infection, in order to avoid selection of more virulent strains. This concept should be considered even in immunocompromised or bedridden children. In case of pyelonephritis, there should be no delay in beginning the antibiotic treatment in order to decrease the risk of long term complication, such as renal scars. Predisposing conditions for UTI, such as voiding anomalies and urinary tract malformation should be carefully evaluated. Expert opinion: One major concern is the increasing resistance to 3rd generation cephalosporins. Therefore overconsumption in low-risk settings should be absolutely avoided. The prevalence of infections with E. coli producing extended spectrum s-lactamase (ESBL) is increasing and pediatricians should be aware about the specific treatment options. Any recommendation about (initial) antibiotic treatment should be regularly updated and adapted to local resistance profiles and to economic factors in different health systems.

Many countries have observed an early and strong impact of implementation of the 13-valent pneumococcal conjugate vaccine (PCV13) on community-acquired pneumonia (CAP). High levels of C-reactive protein (CRP) and procalcitonin (PCT) are considered biomarkers of bacterial infection (particularly infection due to pneumococcus); therefore, PCV13 implementation should have different effectiveness on CAP depending on the levels of these two biomarkers. To demonstrate this assumption, we analyzed the evolution of number of CAP cases seen in pediatric emergency departments in France after PCV13 implementation (in 2010) by levels of these two biomarkers.From June 2009 to May 2015, 8 pediatric emergency units prospectively enrolled all children (1month to 15years) with radiologically confirmed CAP.A cohort of 9586 children with CAP was enrolled (median age 3years). CAP with pleural effusion (PE-CAP) and proven pneumococcal pneumonia (PP-CAP) accounted for 5.5% and 2.0% of cases. During the study period, the number of cases of overall CAP decreased by 25.4%, hospitalized CAP by 30.5%, PE-CAP by 63.4%, CAP with CRP level≥100mg/L by 50.9%, CAP with PCT level≥4ng/L by 60.4% and PP-CAP by 86.4%. We found no change in number of cases of CAP with low levels of CRP (20 or40mg/L) or PCT (0.5ng/mL). The number of cases of CAP overall increased (20.0%) in the last year of the study as compared with the preceeding year but not cases with CRP level≥100mg/L and/or PCT level≥4ng/mL.PCV13 implementation has had a strong impact on number of CAP cases with high levels of CRP and/or PCT in children but no impact on that with low levels of these two biomarkers. Five years after PCV13 implementation, a sustained reduction in CAP cases is observed.

Importance In several countries, 5 years after 13-valent pneumococcal conjugate vaccine (PCV13) implementation, serotype replacement has been reported for invasive pneumococcal disease, which raises concerns about the long-term outcome of PCV13 implementation. The long-term effect of vaccination on community-acquired pneumonia (CAP) remains unknown. Objective To assess the long-term outcome of PCV13 implementation on CAP in children. Design, Setting, and Participants This quasi-experimental, population-based, interrupted time-series analysis was based on a prospective multicenter study conducted from June 2009 to May 2017 in 8 French pediatric emergency departments. All patients 15 years and younger with chest radiography–confirmed CAP were included. Exposures Community-acquired pneumonia. Main Outcomes and Measures The number of CAP cases per 1000 pediatric emergency department visits over time, analyzed usingasegmented regression model, adjusted for influenza-like illness syndromes. Results We enrolled 12 587 children with CAP, including 673 cases of CAP with pleural effusion (5.3%), 4273 cases of CAP requiring hospitalization (33.9%), 2379 cases of CAP with high inflammatory biomarkers (18.9%), and 221 cases of proven pneumococcal CAP (1.8%). The implementation of PCV13 in 2010 was followed by a sharp decrease in the frequency of CAP (−0.8% per month [95% CI, −1.0% to −0.5% per month]), from 6.3 to 3.5 cases of CAP per 1000 pediatric emergency department visits until May 2014, then a slight increase since June 2014 (0.9% per month [95% CI, 0.4%-1.4% per month]), until 3.8 cases of CAP per 1000 pediatric emergency department visits in May 2017. There were marked immediate decreases in cases of CAP with pleural effusion (−48% [95% CI, −84% to −12%]), CAP requiring hospitalization (−30% [95% CI, −56% to −5%]), and CAP with high inflammatory biomarkers (−30% [95% CI, −54% to −6%]), without any rebound thereafter. Conclusions and Relevance The changes associated with PCV13 use 7 years after implementation remain substantial, especially for CAP with pleural effusion, CAP requiring hospitalization, and CAP with high inflammatory biomarkers. Emerging non-PCV13 serotypes may be less likely involved in severe CAP than invasive pneumococcal disease.

IntroductionWhile drug prescription should be based on established recommendations stemming from clinical trials but in pediatrics, many drugs are used without marketing authorization. Consequently recommendations are often based on clinical experience and the risk of inappropriate prescription (IP) is high. A tool for detecting IP in pediatrics-called POPI (Pediatrics: Omission of Prescriptions and Inappropriate prescriptions)-has been developed in France. However the relevance of its use at an international level is not known. Our aim has been to adapt POPI for a worldwide use.Material and methodA two-round Delphi online questionnaire was completed and validated by international experts to identify consensual items. They were asked to rate the validity of each items taking into account the recommendations and practices in their countries. Only propositions obtaining a median score in the upper tertile with an agreement of more than 75% of the panel-for the first round-and 85%-for the second round-were retained.ResultsOur panel included 11 pharmacists (55%) and 9 physicians (45%). The panelists came from 12 different countries: England, Belgium, Brazil, Canada, China, Ivory Coast, Ireland, Malaysia, Portugal, Switzerland, Turkey and Vietnam. At the end of the first round, of the 105 items of the original POPI tool, 80 items were retained including 16 items reworded and 25 items were deleted. In the second round, 14 experts participated in the study. This final international POPI tool is composed of 73 IP and omissions of prescriptions in the fields of neuropsychiatry, dermatology, infectiology, pneumology, gastroenterology, pain and fever.Discussion and conclusionThis study highlights international consensus on prescription practice in pediatrics. The use of this tool in everyday practice could reduce the risk of inappropriate prescription. The impact of the diffusion of POPI tool will be assessed in a prospective multicentric study.

Nitrous oxide (N2O) is widely used as an anesthetic or an analgesic. N2O prolonged and recurrent administration is known to affect vitamin B12 metabolism with subsequent clinical consequences. We report herein the case of a 13-year-old girl with sickle cell disease exhibiting severe neurological and biochemical signs of functional vitamin B12 deficiency due to prolonged and repeated exposure to N2O. This was an incentive to prospectively investigate functional vitamin B12 deficiency in patients affected by sickle cell disease regularly exposed to N2O. We measured plasma concentrations of vitamin B12, total homocysteine, methionine and methylmalonic acid in 39 patients with sickle cell disease between 2015 and 2016. No patients developed neurological symptoms related to N2O administration but 19 patients (49%) had biochemical abnormalities suggesting mildly disturbed vitamin B12 metabolism e.g. decreased B12 vitamin, hypomethioninemia, or slightly increased methylmalonic acid or homocysteine. The clinical case highlight the potential severe deleterious effects of N2O over exposure on B12 vitamin metabolism in particular in patients affected with sickle cell disease. Conversely, when used without excess even repeatedly, there seem to be no overt clinically relevant abnormalities in vitamin B12 metabolism as observed on the cohort of 39 sickle cell disease affected patients., Highlights • Nitrous oxide (N2O) overexposure has a deleterious impact on vitamin B12 metabolism. • Regular use of N2O in sickle cell disease patients can induce minor abnormalities in vitamin B12 metabolism. • N2O administration should be carefully monitored and quantified as any drug. • Functional vitamin B12 deficiency should be investigated prior to N2O administration in at-risk patients.

Aim Studies on bone and joint infections (BJI) in infants under three months are rare. We described the clinical and paraclinical features and outcomes of infants hospitalised with BJI under three months of age. Methods The French National Hospital Discharge Database provided data on BJIs in infants under three months of age from January 2004 to 2015 in three Parisian Paediatric teaching hospitals. Results We included 71 infants under three months of age with BJI, the median age was 25 days, and the interquartile range (IQR) was 17-43 days. The most common infection sites were the hip (32%) and knee (32%). Symptoms included pain (94%), limited mobility (87%) and/or fever (52%). There were 11 (15.5%) cases of nosocomial BJI. A pathogen was identified in 51 infants (71.8%), including Streptococcus agalactiae (45%), Staphylococcus aureus (22%) and Escherichia coli (18%). The initial median C-reactive protein test rate was 31 mg/L (IQR 17-68). Of the 34 infants followed for more than one year, four developed severe orthopaedic conditions such as epiphysiodesis, limb length discrepancy, bone necrosis and/or impaired limb function. Conclusion Streptococcus agalactiae was the most common cause of BJI in infants under three months. Orthopaedic sequelae were rare, but severe, and required long-term follow-up.

International audience; Background: The incidence of meningitis caused by Klebsiella pneumoniae (Kp) and Klebsiella oxytoca (Ko) in high-income countries is unknown, and no series have been published to date.Methods: We conducted a nationwide multicenter observational study in France between 2006 and 2016. All children from the French national registry for paediatric bacterial meningitis under the age of 1 year and hospitalized for Kp or Ko meningitis were included. Virulence factors of four Klebsiella spp. strains were explored by whole genome sequencing.Results: Of 1859 cases of meningitis in children under the age of 1 year, 13 cases (0.7%) of Klebsiella spp. meningitis (nine for Kp meningitis and four for Ko meningitis) were registered in the French national registry. Three of the patients died and 50% of the survivors had developmental delays.Conclusions: Prematurity, low birth weight, and congenital anomalies of the urinary tract appear to be risk factors for Klebsiella spp. meningitis as well as virulence factors of the strain.

ENT infections are the most common childhood infections and the leading causes of antibiotic prescriptions. These infections are mainly due to viruses and most of them (even if bacterial species are implicated) resolve spontaneously. Therefore, the first message is to not prescribe antibiotics in the following situations: common cold, non-streptococcal pharyngitis, laryngitis, non-purulent otitis media, etc. For sore throat/pharyngitis, the antibiotic treatment decision is based mainly on the use of group A streptococcus rapid diagnostic tests. For otitis media, only purulent forms occurring in children less than 2 years of age and most severe situations in older children should be treated with antibiotics. Amoxicillin is the first-line treatment for the vast majority of ENT infections requiring antibiotic treatment. Severe ENT infections (mastoiditis, epiglottitis, retro- and parapharyngeal abscesses, and ethmoiditis) are therapeutic emergencies requiring in most cases hospitalization and intravenous antibiotics.

Bacterial skin and soft tissues infections are common in children and frequently do not require systemic antibiotics, especially if lesions are superficial. Careful washing is always indicated in superficial lesions and is often sufficient. Careful evaluation of symptoms (which may be difficult despite the accessibility of the lesions) should be performed before prescription. Therefore, the need for drainage (spontaneous or surgical) should be assessed considering that antibiotics are mostly useless if purulent lesions are drained. Presence of toxinic symptoms (i.e., generalized cutaneous rash, diarrhea, hypotension) are strongly associated with enhanced severity. The bacterial targets for antibiotics are mainly Staphylococcus aureus (SA) and Streptococcus pyogenes. Considering the low incidence of methicillin-resistant SA in France, the French Pediatric Infectious Disease Group recommends the use of amoxicillin + clavulanate as the first-line antibiotic in most children suffering from severe skin infections requiring antibiotic treatment. In patients presenting toxinic symptoms and signs, the adjunction of an antibiotic with antitoxin properties such as clindamycin should be considered.

We describe the first case of 2 consecutive acute septic arthritis infections of both knees caused by the same virulent strain of Kingella kingae belonging to the virulent sequence type complex 14, in a 16-month-old boy. Both infections occurred after viral upper respiratory tract infections.

Background The effects of ethambutol (EMB) on vision are particularly difficult to detect in children less than 5 years of age because of a lack of complaints and objective clinical signs. The aim of this study was to assess the frequency of visual abnormalities and the utility of visual-evoked potentials (VEPs) recordings in monitoring the visual function of children less than 5 years of age who were exposed to EMB during anti-mycobacterial treatment. Methods We performed a retrospective study in Robert-Debre University Hospital, Paris, France, including all children less than 5 years of age, who were treated with EMB for a mycobacterial infection from January 2002 to December 2012. Results Fourteen patients were enrolled, including 12 treated for Mycobacterium tuberculosis infection. The sex ratio was 1:1. The median age was 1.65 years (0.3 to 4.7). Five patients had subarachnoid involvement. The median EMB dose was 22 mg/kg/day (15 to 27). Only 11 patients were monitored using VEPs. Three children (27.3%) developed a visual impairment secondary to EMB, with delays of 4, 7 and 36 weeks. One of the 3 patients developed an impairment of the retrochiasmatic visual pathways, and 2 other patients developed classical retrobulbar optic neuritis. In all cases, the discontinuation of EMB resulted in a normalization of these findings. Conclusion Alterations in visual function related to the use of EMB are not uncommon in young children and are most likely underestimated. Systematic close monitoring using VEPs recordings is needed in young children treated with EMB.

La Presse Medicale - In Press.Proof corrected by the author Available online since jeudi 5 fevrier 2015

Objective To document more fully the characteristics of chronic recurrent multifocal osteomyelitis (CRMO) in pediatric patients, to collect data on the outcomes and management of the disease, and to define prognostic factors. Methods One hundred seventy-eight patients were included (123 female patients and 55 male patients), with a mean ± SD age at diagnosis of 10.9 ± 2.9 years. Inclusion criteria were a diagnosis of CRMO, evidence of at least one lesion of osteitis confirmed by imaging, and development of the syndrome before age 18 years. Results Longitudinal clinical and imaging studies revealed that only 12 of 178 CRMO patients (7%) had unifocal lesions at the last medical visit. We were able to apply the clinical chronic nonbacterial osteomyelitis score to 110 of 178 patients (62%), which indicated that bone biopsy could have been avoided in 27 cases (25%). At the last medical visit, disease was in remission in only 73 of 171 patients (43%) (41% receiving therapy) after a mean ± SD of 47.9 ± 38.9 months; 44 of 171 patients (26%) experienced sequelae. Using cluster analysis, the CRMO cohort was separated into 3 homogeneous phenotypes (severe, mild, and intermediate). Patients with the severe phenotype had the worst prognosis. This group was entirely composed of male patients, most of whom had the multifocal form of CRMO and inflammatory syndrome. Patients with the mild phenotype had the best prognosis. This group was primarily composed of female patients with a unifocal form of CRMO and infrequent clavicle involvement and inflammatory syndrome. Patients with the intermediate phenotype had a good prognosis but greater reliance on treatment. This group primarily included female patients with multifocal lesions and inflammatory syndrome. Conclusion This is the largest CRMO cohort described in the literature to date. Clinical evolution and imaging investigations confirmed the multifocal pattern of the disease. Three distinct subgroups of CRMO patients were distinguished, with very different prognoses.

Background and objectiveArthritis in children has many causes and includes septic and viral arthritis, reactive arthritis and juvenile idiopathic arthritis (JIA). We aimed to describe the different types of arthritis among children hospitalised for a first episode of arthritis.DesignRetrospective, descriptive case series study.SettingA French tertiary care centre.PatientsChildren under 16 years of age hospitalised for an arthritis episode between 1 January 2008 and 31 December 2009.Main outcome measuresDemographic and clinical features were compared with χ2or Fisher's exact tests and non-parametric tests.Results173 children were hospitalised for a first episode of arthritis during the study period, with a male/female ratio of 1.14. The most frequent cause of hospitalisation was septic arthritis (43.4% of cases, 69.3% of which were due toKingella kingaeand 10.7% toStaphylococcus aureus). JIA was responsible for 8.1% of cases and arthritis without any definitive diagnosis for 40.4%. Median age at diagnosis was 2.7 years (IQR 0.3–14.6) and was lower in the septic arthritis group (1.5 years; 1.1–3.4) than in the JIA group (4.7 years; 2.5–10.9) (pConclusionsSeptic arthritis was the most frequent cause of arthritis in hospitalised children. Despite the increasing application of microbiological molecular methods to synovial fluid analysis, further measures are required to improve the diagnosis of arthritis of unknown cause.

ABSTRACT Aim: Kingella kingae osteoarticular (KKO) infections are frequently associated with upper respiratory tract infections. However, no comparative studies detecting respiratory viruses had ever been performed between KKO and non-KKO (NKO). Patients & methods: Eighteen viruses were searched by FilmArray® Respiratory Panel (BioFire Diagnostics, UT, USA) in the oropharynx of 6-to-48-month-children admitted for KKO and NKO in 2013. Results: At least one virus was detected in the oropharynx of 19/21 (90.5%) KKO and 3/8 (37.5%) NKO cases (p = 0.008). In KKO group, human rhinovirus was predominant (12/21; 57.1%), especially during winter (7/11; 63.6%) despite its low concomitant circulation (

1. INTRODUCTIONThe European Society for Paediatric Infectious Diseases (ESPID) Bone and Joint Infection Guidelines (ESPID Guidelines) are intended for use by health providers who take care of children with bone and joint infection (BJI). Although BJI can include a diverse range of presentations, the

Background: The pharmacokinetic profile of most drugs is dependent on patient's covariates and may be influenced by the disease. Cefotaxime is frequently prescribed in paediatric patients with Sickle Cell Disease (SCD), characterized by vaso-occlusive complications, chronic haemolytic anaemia and defective immunological function predisposing to severe infection. Considering the very particular inflammatory context and the complexity of the disease, one may suspect than SCD could influence the pharmacokinetic profile of many drugs, which has already been reported for the morphine in SCD patients. Data on the impact of SCD on Cefotaxime disposition are missing, while the prescription of an optimal treatment against potentially fatal infections is essential. In the present study, our aims were to determine Cefotaxime pharmacokinetics when prescribed in SCD children for suspected or proven bacterial infection, identify significant covariates and perform Monte-Carlo simulations to optimize drug dosage. Results: Cefotaxime serum concentrations were measured in 80 paediatric SCD patients receiving Cefotaxime. A total of 110 concentrations were available for pharmacokinetic analysis. The population pharmacokinetic model developed from the SCD samples analyze made it possible to predict the plasma concentrations obtained according to the prescribed dosages. We found that the prescription of a standard dose of Cefotaxime (50 mg/kg every 8 hours) or a high dose of Cefotaxime (50 mg/kg every 6 hours) were both insufficient to reach the therapeutic target (ie a time above the minimum inhibitory concentration of the germ (T>MIC) of 80%, which is recommended for severe bacterial infection), particularly in young children (Figure 1) . With the standard dose of Cefotaxime, only 38% of patients under 12 years old reached the therapeutic target, which increase to 82% with a high dose, meaning that 18% of the patients are still not efficiently treated in case of bacteria infection. In case of germs (Streptococcus pneumoniae or Salmonella) with intermediate sensitivity (MCI=1g/l), the amount of underdosed patients could reach 81% with the prescription of a standard dose (Figure 1). Moreover, Cefotaxime clearance increased by 22% in patients with acute chest syndrome, highlighting the possible impact of severe vaso-occlusion and inflammation on drug metabolism. Conclusion: Our data suggest that SCD patients, particularly young children, may have a particular Cefotaxime pharmacokinetic profile, possibly due to severe inflammatory condition. Considering the predisposition to severe infection in these patients, the prescribed dose of Cefotaxime should not be lower than 50 mg/kg/6h. In case of acute chest syndrome, this dose could even be insufficient to treat a bacterial infection (including due to sensitive germ with MIC= 0.5g/L or below) and should be adapted depending on patients' characteristics and clinical presentation. Disclosures No relevant conflicts of interest to declare.

The group A streptococcus (GAS) is the 5(th) responsible pathogen of invasive infections in children in France. These particularly severe diseases are dominated in children by soft tissue infection, isolated bacteremia but also osteoarthritis. Other complications are rare in France such as lung infections, necrotizing fasciitis (NF) and streptococcal toxic shock syndrome (STSS). More unusual localizations such as meningitis, neonatal infections, severe ear and throat and gastrointestinal infections and vascular disorders are also described. Based on published series, mortality ranging from 0-8 % of cases, is high but still lower than that observed in adults. Probabilistic antibiotherapy includes a β-lactam with anti-SGA but also anti-staphylococcal (predominantly methi-S in France) activity such as clavulanic acid- amoxicillin followed by amoxicillin as soon as identification of SGA is performed. The addition of an anti-toxin antibiotic such as clindamycin is recommended particularly in NF or STSS or clinical signs suggestive of toxin production by the SGA (rash, gastrointestinal signs, hemodynamic disorders). The use of intravenous polyvalent immunoglobulins must also be discussed in NF and STSS. In all cases surgery should be discussed. The prognosis of these potentially very severe infections is related to their early diagnosis and treatment. A better understanding of the pathophysiology of these infections may optimize their management but also their prevention.

Septic arthritis has to be suspected in children with joint effusion and fever so as to perform joint aspiration, which will confirm the diagnosis by bacteriological methods, and to perform surgical treatment by joint lavage. Since development of current molecular methods, such as real-time PCR, Kingella kingae has become the first microbial agent of osteoarticular infections in young children, whereas Staphylococcus aureus is second. C-reactive protein (CRP) is an aid used to diagnose septic arthritis, but its elevation could be moderate. In a previous study, conducted at our hospital, 10% of children hospitalized for S. aureus or K. kingae septic arthritis had a CRP level 10 mg/L during septic arthritis in children, it could be negative in up to 20% of patients in different studies. However, a mild inflammatory syndrome or even a CRP

Objectives This article analyses antimicrobial use in three tertiary-care paediatric hospitals with the aim of improving antimicrobial stewardship in paediatric hospitals. Methods A point prevalence survey (PPS) was undertaken during November 2012 using validated and standardised ARPEC (Antibiotic Resistance and Prescribing in European Children) methodology. The data collected contributed to the ARPEC study. Results Antimicrobials were prescribed to 116 patients (48%) in Birmingham, 114 (38%) in Paris and 128 (37%) in Riga. Respiratory tract infections were the most common indications for antibiotic use in Riga, but in Birmingham and Paris antibiotics were used most for prophylaxis in case of medical problems. The most common age group of patients receiving antimicrobials across all three sites was children aged 1–5 years old: there were 41 (35%) children in this age group in Birmingham, 37 (32%) in Paris and 36 (28%) in Riga. The most common antimicrobial used for the treatment and prophylaxis of paediatric patients was cotrimoxazole in Birmingham and Paris and ceftriaxone in Riga. Antimicrobials were mainly used parenterally: there were 100 (55%) parenteral prescriptions in Birmingham, 122 (50%) in Paris and 111 (75%) in Riga. Conclusions The PPS identified differences in antimicrobial use in the three hospitals and problem areas requiring improvement: high use of thirdgeneration cephalosporins for paediatric patients (especially in Riga) and predominant use of parenteral antibiotics. Further collaboration between pharmacists operating at each site is needed in order to improve antimicrobial stewardship initiatives.