Abstract Background Pneumococcal nasopharyngeal colonization is the first step toward invasive pneumococcal disease (IPD). Respiratory syncytial virus (RSV) may trigger IPD, particularly for serotypes with low disease potential. We aimed to analyze the distribution of pneumococcal serotypes among pediatric IPD according to RSV circulation level. Methods We used data from 3 continuous French surveillance systems on IPD, pneumococcal carriage and RSV infections from 2008 to 2023. Based on the RSV epidemic threshold, we assessed the proportion of each serotype among IPD, depending on “RSV season” and “non-RSV season.” We assessed the correlation between the likelihood of serotype-specific involvement in IPD according to non-RSV season versus RSV season and the estimated disease potential of each serotype. Results Among 4574 IPD cases, the serotype distribution strongly varied during non-RSV season versus RSV season. The lower the disease potential of serotypes, the more RSV circulation enhanced their involvement in IPD (Rho=0.60, CI95% .28–.80, P = .0012). Conclusions The role of RSV in triggering IPD strongly varies across pneumococcal serotypes. The impact of RSV-targeted interventions should be evaluated in light of these data.

Objective: To investigate clinical and microbiological factors associated with persistent faecal carriage of extended spectrum beta-lactamase (ESBL) producing Escherichia coli in infants.Methods: Between 2010 and 2022, children aged 3 months to 2 years old were sampled in a community setting in France, at two visits, V1 and V2, 3 to 24 months apart, to screen for prolonged faecal carriage of ESBL-producing E. coli. Patient clinical information and whole genome sequence of each isolate were used for association studies.Results: A total of 4641 children were sampled. 375 (8%) carried an ESBL-producing Enterobacterales, among which 142 of ESBL-producing E. coli carriers were once again sampled at V2 and included in this study. 21.8% (n=31/142) and 18.4% (n=16/99) carried the same ESBL-producing E. coli clone for at least 3 and 6 months, respectively. B2 phylogroup, and among which ST131 clones were associated with an increased risk of persistent carriage. Multivariate analysis identified virulence associated genes involved in adhesion (papC/papGII allele and a tia-like gene) and encoding toxin (senB) as major risk factors for persistence. A genome wide association study highlighted the potential role of the frz metabolic operon, known to be involved in enterocytes adhesion/internalization.Conclusion: Main extraintestinal pathogenic E. coli genomic features (phylogenetic background, adhesion properties) are associated with ESBL-producing E. coli gut colonisation persistence in infants, which could potentially lead to an increased risk of febrile urinary tract infection in these patients.

BACKGROUND:Pneumococcal nasopharyngeal colonization is the first step toward invasive pneumococcal disease (IPD). Respiratory syncytial virus (RSV) may trigger IPD, particularly for serotypes with low disease potential.We aimed to analyse the distribution of pneumococcal serotypes among paediatric IPD according to RSV circulation level. METHODS:We used data from three continuous French surveillance systems on IPD, pneumococcal carriage and RSV infections from 2008 to 2023. Based on the RSV epidemics threshold, we assessed the proportion of each serotype among IPD, depending on "RSV season" and "non-RSV season". We assessed the correlation between the likelihood of serotype-specific involvement in IPD according to non-RSV season vs RSV season and the estimated disease potential of each serotype. RESULTS:Among 4,574 IPD cases, the serotype distribution strongly varied during non-RSV season vs RSV season. The lower the disease potential of serotypes, the more RSV circulation enhanced their involvement in IPD (Rho=0.60, CI95% 0.28 to 0.80, p-value = 0.0012). CONCLUSIONS:The role of RSV in triggering IPD strongly varies across pneumococcal serotypes. The impact of RSV-targeted interventions should be evaluated in light of these data.

BACKGROUND:Fusobacterium necrophorum is primarily involved in ear, nose and throat (ENT) infections, and exceptionally causes meningitis. We aimed at describing specific clinical features associated with cases of F. necrophorum meningitis. METHODS:Cases of F. necrophorum meningitis were prospectively collected by a network of 259 pediatric wards covering 60% of French pediatric wards between 2001 and 2024. Children were categorized in 2 groups: "isolated" meningitis and "complicated" meningitis, defined by ≥1 local or systemic complication (mastoiditis, subperiosteal or epidural abscess, Lemierre syndrome). RESULTS:A total of 27 cases of F. necrophorum meningitis were recorded. Median age was 4 years old (2-7 years) and only 2 were <1 year old. All children had a previous ENT infection, mainly acute otitis media (N = 21/27). Fusobacterium necrophorum was isolated in the cerebrospinal fluid (CSF) by culture (N = 16) or by polymerase chain reaction (PCR) (N = 3). One child had a positive 16S rRNA PCR in a cerebral abscess; other children had a CSF pleocytosis with a positive blood culture. Twenty children had a "complicated" meningitis, while 7 an "isolated" one. Median age was 4 years old in both groups. In the complicated group, 12 children underwent surgical drainage and 4 died. None of these children had a previous medical history. CONCLUSIONS:Our study highlights that, in addition to the well-known Lemierre syndrome, F. necrophorum should be considered in children ≥1 year old presenting with meningitis associated with acute otitis media, particularly when direct CSF examination or usual multiplex PCR fails to identify any bacteria. In such cases, 16S rRNA PCR and antibiotic treatment targeting anaerobic bacteria should be considered.

Background Acute otitis media (AOM) is the leading cause of antibiotic prescription in children. Respiratory syncytial virus (RSV) is suspected to play an important role in AOM. The aim of this study was to estimate the impact of RSV immunization on the rate of subsequent AOM in children, as this effect remains unknown. Methods We conducted an interrupted time-series analysis based on a French network involving 110 ambulatory pediatricians, trained in pediatric infectious diseases (PARI network). All ambulatory visits for AOM, from June 2017 to February 2025 were included. The main outcome was the monthly rate of pediatric ambulatory visits for AOM in infants aged < 12 months per 1000 pediatric ambulatory visits over time, assessed by a seasonally adjusted quasi-Poisson regression model. Bronchiolitis and urinary tract infections (UTI) were analyzed over the same period, as positive and negative controls, respectively. Results We included 70 452 cases of AOM, 13 284 bronchiolitis and 814 UTI. The rate of AOM per 1000 visits in infants aged < 12 months significantly decreased after RSV immunization implementation (-23.7%, 95% CI -37.6 to -9.7, P = .0014), whereas no significant change was observed in older age groups. We observed similar trends for bronchiolitis. The monthly rate of UTI did not significantly decrease. Conclusions RSV immunization led to a strong reduction of AOM rate in infants aged < 12 months. Beyond its efficacy in preventing RSV-related lower respiratory infections in infants aged < 12 months, RSV immunization may contribute to reduce the burden of AOM in children.

CONTEXT:Nirsevimab was implemented in Europe and the United States in September 2023. While its effectiveness in preventing respiratory syncytial virus (RSV)-bronchiolitis has been demonstrated by real-life studies, its impact on mid-term child health, quality of life, and parental absenteeism remains unstudied. METHODS:Infants under 1-year with a first bronchiolitis episode were recruited through the OURSYN study involving 37 primary care pediatricians in France between 2021 and 2025 (pre-nirsevimab period: 02/2021-03/2023 and nirsevimab period: 09/2023-03/2025). RSV status was determined by antigenic nasopharyngeal testing. At day 15, parents reported symptoms, quality of life (PedsQL Infant), and work absenteeism. Their associations with (i) RSV status, (ii) period of inclusion, and (iii) nirsevimab immunization status among RSV-positive cases were assessed using multivariable logistic regression adjusted for confounders. RESULTS:Among 1870 bronchiolitis cases included, 637 (34.0%) occurred during the nirsevimab period and 812 (43.4%) were RSV-related. Over the study period, at day 15, RSV-cases had more feeding difficulties (aOR = 1.41 [1.06-1.88]), longer daycare absence (4.7 vs. 3.2 days), and more parental absenteeism (aOR = 1.61 [0.99-2.62]) compared to RSV-negative. The proportion of RSV-cases decreased during the nirsevimab period compared with the pre-nirsevimab period (47.1% vs. 35.7% P < .001). Bronchiolitis cases recruited during this period had shorter daycare absences (3.2 vs. 4.3 days). Among RSV-cases, immunized infants had lower risk of persistent fever (aOR = 0.14 [0.01-0.79]). CONCLUSION:This large prospective study provides the first evidence that the mid-term burden of RSV-bronchiolitis in infants may be reduced following the implementation of nirsevimab, with potential benefits for infant health, quality of life and parental absenteeism.

Background:Community-acquired bacterial infections (CABIs) remain a leading cause of pediatric morbidity and mortality. This study aimed to provide a contemporary description of pediatric CABIs requiring admission to pediatric intensive care units (PICUs) in France. Methods:The CAPRICE study is a prospective, multicenter cohort including all children with suspected CABIs who were admitted to 28 French PICUs from January to December 2024. Demographic, clinical, microbiologic, and outcome data were prospectively collected. The primary outcome was mortality at day 28 and secondary outcomes included sequelae at day 28, PICU length of stay, and total hospital stay. Independent predictors of mortality were identified by multivariable logistic regression. Results:Among 897 children, the median age was 1.9 years (IQR 0.2-8.8); 55% were male, and 30% had a chronic condition. The leading infections were lower respiratory tract infection (43%), meningitis (20%), and ear-nose-throat infections (13%). Septic shock occurred in 17% of cases. A pathogen was identified in 89% of cases: Bordetella pertussis (22%) and Mycoplasma pneumoniae (15%) were predominant, followed by Streptococcus pneumoniae (13%), and Staphylococcus aureus (11%). In all, 34% patients had viral co-infection and 70% required organ support. Overall mortality was 7%, increasing to 19% with septic shock. Independent predictors of death included multiple organ failure, meningitis, and B. pertussis infection. Sequelae occurred in 15% of survivors. Conclusions:Severe CABIs in French PICUs in 2024 were mainly caused by B. pertussis and M. pneumoniae, followed by S. pneumoniae and S. aureus. Mortality and morbidity of these infections remain substantial.

BACKGROUND:Cerebrospinal fluid (CSF) leakage is a recognized risk factor for bacterial meningitis. Few data are published concerning bacterial meningitis in children with CSF leakage, and the impact of 13 valent pneumococcal conjugate vaccination (PCV13) in this population is not well known. The aim of this study was to describe the epidemiology of bacterial meningitis in children with known CSF leakage. METHODS:Among all bacterial meningitis in children >3 months old, we analyzed those with known CSF leakage (meningeal breach and/or cochlear implant resulting in meningitis) in a nationwide prospective cohort between 2001 and 2024 in France, with 227 pediatric wards and 168 microbiology departments. RESULTS:Of 5879 cases of bacterial meningitis in children over 3 months old, 251 (4.3%) were associated with known CSF leakage. In this population, Streptococcus pneumoniae (78.9%) was the most frequent bacteria involved, followed by Haemophilus influenzae (10%), mainly non typeable strains. Two cases of Neisseria meningitidis were recorded and only in children with cochlear implant. For children with known CSF leakage, in late PCV13 period, PCV13, PCV15, PCV20, PCV21, and 23-valent polysaccharide vaccine serotypes accounted for 14%, 16.3%, 37.2%, 79.1%, and 27.9%, respectively. In this population, serotype 23B was the most frequent (18.6%), followed by 11A (9.3%), 15A (9.3%), 19F (7%), 3 (4.7%), and 19A (2.3%). CONCLUSION:Bacterial meningitis in children with known CSF leakage is largely due to pneumococci and now mainly due to serotypes not included in PCV13. Only two cases of meningococcal meningitis were found and only for children with cochlear implant.

Abstract The worldwide rise in the prevalence of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli is a major public health concern. In Europe, ESBL carriage frequency increased then stabilized at about 6-8 %. Past antibiotic use and travel in countries with high ESBL frequency, notably South-East Asia, have repeatedly been identified as risk factors of ESBL carriage. Yet, the relative contributions of these mechanisms to the observed maintenance of a stable low frequency of ESBL in Europe remains unknown. Here, we used comprehensive data on the risk factors for carriage of ESBL-producing E. coli in the French community, alongside detailed microbiological characterization of both resistant and overall E. coli , to develop a biologically plausible mathematical model of ESBL resistance spread in France. The model also includes several mechanisms previously showed to favor coexistence such as population structure, variability in carriage duration and within-host dynamics. The level of resistance in the community implies resistant strains transmit 14% less than sensitive (95% credible interval 0.6-38%), and are cleared at a +23% larger rate (0.9-62%). ESBL resistance is predicted to be strongly associated with factors prolonging residence in the gut. Both the rate of antibiotic treatment and transmission strongly impact the frequency of ESBL in the community. In contrast, travel has little impact on ESBL frequency. Whether reducing treatment or transmission is best to reduce resistance depends on community-specific parameters. Our study opens perspectives for the quantitative study of resistance evolution and argues for future work to improve the characterization of the duration of carriage of commensal bacterial strains.

OBJECTIVE:To estimate the effectiveness of nirsevimab against respiratory syncytial virus (RSV)-associated acute otitis media (AOM) in ambulatory care. STUDY DESIGN:We conducted a test-negative design study, post hoc analysis using data from the prospective Oursyn study involving 37 primary care pediatricians across France from 2020 to 2025. Nasopharyngeal sampling for RSV was performed in infants younger than 1 year diagnosed with AOM during the first 2 RSV seasons with introduction of nirsevimab passive immunization (October 2023 to February 2024 and October 2024 to January 2025). The main outcome of the study was the detection of RSV status in infants with AOM. We performed a multivariable logistic regression with nirsevimab adjusted for age, sex, underlying chronic condition, prematurity, type of childcare, month, year, and geographic region of inclusion. Sensitivity analyses were performed as well. RESULTS:A total of 236 AOM events were included over the study period: 141 during the first season of nirsevimab implementation and 95 during the second season. Among infants with AOM, 41 (29.1%) and 15 (15.8%), respectively, tested positive for RSV. Nirsevimab-adjusted effectiveness was estimated to be 78.2% (95% CI 44.4-92.4) for the prevention of RSV-AOM in this sample. Sensitivity analyses found similar results. CONCLUSIONS:These findings highlight the broader protective effect of nirsevimab on complications of respiratory tract infections in infants. TRIAL REGISTRATION:NCT04743609.

BACKGROUND:Nasopharyngeal carriage of major respiratory bacterial pathogens plays a key role in respiratory infections and transmission. While most carriage studies focus on preschool children, data beyond the age of 6 years remain scarce. This 11-year multicenter study provides a unique overview of carriage dynamics in children up to 15 years old during the Pneumococcal Conjugate Vaccine 13-valent (PCV13) era. METHODS:Nasopharyngeal swabs (2013-2024) from 6420 healthy children aged 6 months to 15 years were collected by 87 pediatricians across France. Standard culture identified Streptococcus pneumoniae (Sp), Haemophilus influenzae (Hi), Moraxella catarrhalis (Mc) and Staphylococcus aureus (Sa); pneumococci were serotyped by latex agglutination, and age-specific carriage patterns were analyzed by cross-sectional comparison. RESULTS:Overall pneumococcal carriage was 28.6%, remaining high up to 5 years of age (≈38%) before declining to ~10% in older children. Non-PCV13 serotypes predominated (23B, 11A, 23A, 15B and 35B), but PCV13 serotypes persisted in 10.4% of pneumococcal carriers and 2.9% of children. Serotypes 19A and 19F remained stable across ages, whereas serotype 3 markedly increased, becoming one of the most prevalent in older children. Hi and Mc carriage mirrored pneumococcus patterns in early childhood but declined with age, while Sa carriage rose inversely. Co-carriage of Sp with Hi or Mc was frequent but rare with Sa, independent of age. CONCLUSIONS:Sp, Hi and Mc carriage remains high up to 5 years of age and declines quickly afterward, whereas Sa shows an inverse pattern. The persistence of serotypes 19A, 19F and the increasing prevalence of serotype 3 in older children may act as a reservoir fueling invasive pneumococcal infections in adults, underscoring the need for continued surveillance and next-generation vaccine strategies.

BACKGROUND:Multisystem inflammatory syndrome in children (MIS-C) is a severe postinfectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, primarily affecting children aged 6-12 years. Although MIS-C was prominent during the early pandemic waves, recent studies suggest a declining incidence concurrent with increasing reinfection rates. The objective was to determine whether the risk of MIS-C differs following a primary SARS-CoV-2 infection versus reinfection. METHODS:A retrospective, multicenter, international, matched case-control study was conducted from September 1, 2021, to April 30, 2022. MIS-C cases were recruited from 14 French and Swiss hospitals. Eligible cases included children younger than 18 years meeting the 2020 World Health Organization case MIS-C definition with laboratory evidence of SARS-CoV-2 infection. Cases were matched 1:1 by age, sex and epidemic period to controls with laboratory-confirmed acute SARS-CoV-2 infection. Vaccinated patients and those without consent were excluded. The primary outcome compared the association of reinfection with MIS-C versus acute infection using McNemar's test to estimate matched odds ratios (ORs). Prespecified sensitivity analyses used conditional logistic regression. RESULTS:The matched cohort included 180 MIS-C cases (median [IQR] age, 106 [62-136] months) and 180 controls (median [interquartile range] age, 72 [48-108] months). No MIS-C cases had a documented reinfection, whereas 3.9% (7/180) of controls did (McNemar χ2 = 5.142; P = 0.023; matched OR, 0.067; 95% confidence interval [0.004-1.167]; P = 0.064). Sensitivity analysis also suggested a lower odds of MIS-C after reinfection without reaching statistical significance (adjusted OR, 0.183; 95% [0.027-1.234]; P = 0.093). CONCLUSION:MIS-C occurred predominantly after first SARS-CoV-2 infections; while evidence for a lower risk following reinfection was suggestive but not conclusive.

Among 7578 cases of pediatric bacterial meningitis recorded in France (2001-2021), including 1313 neonatal cases, 23/7578 (0.3%) and 18/1313 (1.4%) were due to Citrobacter koseri. Median age was 11 days. About 63.6% of patients were hospitalized in intensive care unit. Cerebral abscesses were observed in 77.8% and the mortality rate was 22.7%.

BACKGROUND:Following a decline during the COVID-19 pandemic, Mycoplasma pneumoniae infections resurged in several countries. We aimed to characterise the clinical presentation of paediatric patients admitted to hospital for M pneumoniae during 2023 and 2024 in France. METHODS:We conducted a nationwide, multicentre, retrospective, and prospective observational study across 37 French paediatric hospitals (September, 2023-September, 2024). Children younger than 18 years who were hospitalised with laboratory-confirmed M pneumoniae infection (PCR or serology) were included. Demographics (excluding race), clinical features, laboratory and radiological findings, management, and outcomes data were described and analysed. Logistic regression was used to identify factors associated with paediatric intensive care unit (PICU) admission. The trial was registered at ClinicalTrials.gov (NCT06260371) and is complete. FINDINGS:We included 969 children and adolescents with M pneumoniae infection (7·3 years [SD 4·5], 426 [44%] of 966 patients were female and 540 [56%] of 966 were male). 936 (97%) of all patients were positive by PCR for M pneumoniae. Pneumonia was diagnosed in 628 (87%) of the 726 patients with respiratory involvement, and cutaneous manifestations were reported in 132 (14%) of 969 patients, including 56 (42%) of 132 who had erythema multiforme. Macrolides were prescribed in 884 (95%) of the 931 patients who were prescribed antibiotics, primarily azithromycin (563 [64%] of 884). Macrolide resistance was detected in one (5%) of the 21 tested samples. In total, 57 (6%) of 969 patients required PICU admission and four (<1%) died. Factors significantly associated with PICU admission included being older than 11 years (adjusted odds ratio 2·0 [95% CI 1·1-3·6]; p=0·023), asthma (2·2 [1·2-4·0]; p=0·0072), other underlying conditions (2·1 [1·2-3·7]; p=0·013), and erythema multiforme (3·7 [1·6-8·8]; 0·0025). INTERPRETATION:The 2023-2024 M pneumoniae epidemic in France resulted in a substantial paediatric hospitalisation burden. Although severe cases were uncommon, children older than 11 years, those with asthma, other comorbidities, and erythema multiforme were at increased risk of PICU admission. Ongoing surveillance and targeted management strategies are warranted for future epidemics. FUNDING:Association Clinique et Thérapeutique Infantile du Val de Marne (ACTIV).

Regarding nirsevimab immunization status, among 1085 infants hospitalized for bronchiolitis, the odds of hospitalization for respiratory syncytial virus bronchiolitis were 4.7 times higher for nonimmunized children. Immunized infants were less likely to require oxygen supplementation (20.2% vs. 30.6%, P = 0.02) and had a 1-day shorter hospital stay. Respiratory syncytial virus bronchiolitis was less frequent and less severe in infants immunized with nirsevimab.

We describe the characteristics of children hospitalized for coronavirus disease 2019 in France with a focus on the post-BA.1 Omicron period (February 2022–December 2023). We identified 3 main groups of children: those ≤90 days old (44.8%), older children with comorbidities (22.1%) and children with multisystem inflammatory syndrome (5.2%). Low vaccination coverage in these groups suggests that this burden could be alleviated with immunization.

Severe cardiovascular involvement is associated with mortality in multisystem inflammatory syndrome in children (MIS-C). This study aimed to test a previously published cardiogenic shock risk score at diagnosis of MIS-C and build a new screening tool in a larger pediatric cohort. The first score published in a single-center cohort (age > 8 years, time to diagnosis ≥ 6 days, and NT-proBNP at diagnosis ≥ 11.103 ng/L) was tested in a multicenter cohort of pediatric patients diagnosed with MIS-C from 2020 to 2023. In the multicenter cohort, the factors associated with the occurrence of cardiogenic shock were determined and a new score was built using a multivariate regression model. In 127 children with MIS-C, (median age [interquartile range] 8.6 [5.2; 11.5] years, 67 (53

Importance:New resistant mutations of respiratory syncytial virus type B (RSV-B) have been observed during the first year of implementation nirsevimab treatment. During the second season of implementation of nirsevimab treatment in France, RSV-B was predominant. Objectives:To assess and compare the effectiveness of nirsevimab treatment in preventing RSV bronchiolitis in pediatric emergency departments during the first and second seasons of implementation of treatment in France. Design, Setting, and Participants:This a multicenter test-negative case-control study included 636 infants younger than 1 year who received a diagnosis of a first bronchiolitis episode in 5 pediatric emergency departments in France during the 2 first seasons of implementation of nirsevimab treatment (from October 5, 2023, to February 29, 2024, and from October 15, 2024, to January 31, 2025) and underwent a nasopharyngeal test for RSV. Main Outcomes and Measures:The main outcome of the study was the RSV status of the bronchiolitis cases. Multivariable logistic regression was performed with nirsevimab as the explanatory variable, adjusted on age, sex, risk factors of bronchiolitis, type of childcare, month, and center of inclusion. Effectiveness was calculated for each season and compared using the likelihood ratio test. Subgroup analysis by age and severity as well as sensitivity analyses were performed. Results:The study included 636 patients with bronchiolitis (median age, 3.0 months [IQR, 1.4-5.0 months]; 333 boys [52.4%]). In both seasons, 162 of 636 patients (25.5%) were immunized with nirsevimab. During the first season of implementation, 273 of 384 patients (71.1%) tested positive for RSV; during the second season, 181 of 252 patients (71.8%) tested positive for RSV. The effectiveness of nirsevimab treatment against RSV bronchiolitis was estimated to be 83.2% (95% CI, 68.0%-91.4%) during the first season and 89.3% (95% CI, 77.8%-95.1%) during the second season; no statistically significant difference in effectiveness was found between the 2 seasons (P = .97). Subgroup and sensitivity analyses provided similar results. Conclusions and Relevance:In this test-negative case-control study of nirsevimab treatment, its effectiveness in reducing pediatric emergency department visits for RSV bronchiolitis during the second season of national immunization was high and comparable with that observed in the first season. Although RSV-B resistant strains had been recently identified, it did not appear to have important clinical consequences to date. Continued close monitoring of RSV epidemiology in the context of the widespread nirsevimab use remains essential.