Nirsevimab and Hospitalization for RSV Bronchiolitis.

BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis, resulting in 3 million hospitalizations each year worldwide. Nirsevimab is a monoclonal antibody against RSV that has an extended half-life. Its postlicensure real-world effectiveness against RSV-associated bronchiolitis is unclear. METHODS: We conducted a prospective, multicenter, matched case-control study to analyze the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis in infants younger than 12 months of age. Case patients were infants younger than 12 months of age who were hospitalized for RSV-associated bronchiolitis between October 15 and December 10, 2023. Control patients were infants with clinical visits to the same hospitals for conditions unrelated to RSV infection. Case patients were matched to control patients in a 2:1 ratio on the basis of age, date of hospital visit, and study center. We calculated the effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis (primary outcome) by means of a multivariate conditional logistic-regression model with adjustment for confounders. Several sensitivity analyses were performed. RESULTS: The study included 1035 infants, of whom 690 were case patients (median age, 3.1 months; interquartile range, 1.8 to 5.3) and 345 were matched control patients (median age, 3.4 months; interquartile range, 1.6 to 5.6). Overall, 60 case patients (8.7%) and 97 control patients (28.1%) had received nirsevimab previously. The estimated adjusted effectiveness of nirsevimab therapy against hospitalization for RSV-associated bronchiolitis was 83.0% (95% confidence interval [CI], 73.4 to 89.2). Sensitivity analyses gave results similar to those of the primary analysis. The effectiveness of nirsevimab therapy against RSV-associated bronchiolitis resulting in critical care was 69.6% (95% CI, 42.9 to 83.8) (27 of 193 case patients [14.0%] vs. 47 of 146 matched control patients [32.2%]) and against RSV-associated bronchiolitis resulting in ventilatory support was 67.2% (95% CI, 38.6 to 82.5) (27 of 189 case patients [14.3%] vs. 46 of 151 matched control patients [30.5%]). CONCLUSIONS: In a real-world setting, nirsevimab therapy was effective in reducing the risk of hospitalized RSV-associated bronchiolitis. (Funded by the National Agency for AIDS Research-Emerging Infectious Disease and others; ENVIE ClinicalTrials.gov number, NCT06030505.).

Saliva for molecular detection of SARS-CoV-2 in pre-school and school-age children.

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.

Multisystem inflammatory syndrome in children rose and fell with the first wave of the COVID-19 pandemic in France.

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.

Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020.

BackgroundChildren have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections.AimWe 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.MethodsWe 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.ResultsPrevalence 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.ConclusionPrior infection by seasonal coronaviruses, as assessed by serology, does not interfere with SARS-CoV-2 infection and related MIS in children.

Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children.

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.

Cardiac MRI in Children with Multisystem Inflammatory Syndrome Associated with COVID-19.

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.

Bone and joint infections in infants under three months of age.

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.

Population Pharmacokinetics of Cefotaxime and Dosage Recommendations in Children with Sickle Cell Disease.

The pharmacokinetic profile of most drugs is dependent on the patient's covariates and may be influenced by the disease. Cefotaxime is frequently prescribed in pediatric patients with sickle cell disease (SCD), characterized by vaso-occlusive complications, chronic hemolytic anemia, and a defective immunological function predisposing the individual to severe infection. Data on the impact of the disease on the disposition of cefotaxime are missing. In the present study, our aims were to determine cefotaxime pharmacokinetics when prescribed to children with SCD for suspected or proven bacterial infection, identify significant covariates, and perform Monte Carlo simulations to optimize the drug dosage. Cefotaxime serum concentrations were measured in 78 pediatric SCD patients receiving cefotaxime intravenously at a daily dose of 200 mg/kg of body weight in three or four divided doses over 30 min. A total of 107 concentrations were available for pharmacokinetic analysis. A population pharmacokinetic model was developed with NONMEM software and used for Monte Carlo simulations. Cefotaxime concentrations ranged from 0.05 to 103.7 mg/liter. Cefotaxime pharmacokinetics were best described by a one-compartment model: the median estimated weight-normalized volume of distribution and clearance were 0.42 liter/kg (range, 0.2 to 1.1 liter/kg) and 0.38 liter/h/kg (range, 0.1 to 1.2 liter/h/kg). Cefotaxime clearance increased by 22% in patients with acute chest syndrome. Dosing optimization, performed using EUCAST MIC susceptibility breakpoints, showed that a dose of 100 mg/kg/6 h should be used, depending on the patient's characteristics and clinical presentation, in order to reach a value of the percentage of time that the drug concentration exceeded the MIC under steady-state pharmacokinetic conditions of 80% in 80% of the patients when targeting sensitive Gram-positive cocci and Gram-negative bacilli with MICs of 1 mg/liter or below.

Invasive pneumococcal disease in children can reveal a primary immunodeficiency.

BACKGROUND: About 10% of pediatric patients with invasive pneumococcal disease (IPD) die from the disease. Some primary immunodeficiencies (PIDs) are known to confer predisposition to IPD. However, a systematic search for these PIDs has never been carried out in children presenting with IPD. METHODS: We prospectively identified pediatric cases of IPD requiring hospitalization between 2005 and 2011 in 28 pediatric wards throughout France. IPD was defined as a positive pneumococcal culture, polymerase chain reaction result, and/or soluble antigen detection at a normally sterile site. The immunological assessment included abdominal ultrasound, whole-blood counts and smears, determinations of plasma immunoglobulin and complement levels, and the evaluation of proinflammatory cytokines. RESULTS: We included 163 children with IPD (male-to-female ratio, 1.3; median age, 13 months). Seventeen children had recurrent IPD. Meningitis was the most frequent type of infection (87%); other infections included pleuropneumonitis, isolated bloodstream infection, osteomyelitis, endocarditis, and mastoiditis. One patient with recurrent meningitis had a congenital cerebrospinal fluid fistula. The results of immunological explorations were abnormal in 26 children (16%), and a PID was identified in 17 patients (10%), including 1 case of MyD88 deficiency, 3 of complement fraction C2 or C3 deficiencies, 1 of isolated congenital asplenia, and 2 of Bruton disease (X-linked agammaglobulinemia). The proportion of PIDs was much higher in children aged >2 years than in younger children (26% vs 3%; P < .001). CONCLUSIONS: Children with IPD should undergo immunological investigations, particularly those aged >2 years, as PIDs may be discovered in up to 26% of cases.

Fluoroquinolones in pediatrics: review of hospital prescription use over 2 years.

OBJECTIVE: Numerous studies have shown that the tolerance of children to fluoroquinolones (FQs) is satisfactory, and some indications have been recently agreed upon. However, vigilance is required when prescribing FQ to children. The aim of our study was to describe the prescription of FQs to children hospitalized in our hospital. MATERIALS AND METHODS: This is a chart retrospective observational study at the Robert-Debré teaching Hospital between January 2009 and December 2010. Data was collected about patients (name, sex, weight, age) and prescribed treatments (indication, international nonproprietary names, dose, number of doses per day, administration route). Quality of collected data was assessed by analyzing the clinical files of 32 randomly selected patients. RESULTS: We analyzed data for 397 patients (3 days - 18 years old and 640 g - 115 kg). Ciprofloxacin was prescribed for 382 patients (96%), ofloxacin for 10 patients (3%), and levofloxacin for 5 patients (1%). Febrile neutropenia was the most common indication (108 patients, i.e., 27%), followed by inflammatory bowel disease (50 patients, 13%). Doses conformed to recommendations for 88% of the patients. Analysis of the 32 cases indicated an overall compliance percentage of 94.4%. CONCLUSION: This is the first study to collect so much data on FQ prescriptions for hospitalized children. Use in practice went beyond the licensed indication. Doses were consistent with those for recommended indications.

Pediatric gastroenteritis in the emergency department: practice evaluation in Belgium, France, The Netherlands and Switzerland.

BACKGROUND: Based on European recommendations of ESPGHAN/ESPID from 2008, first line therapy for dehydration caused by acute gastroenteritis (AGE) is oral rehydration solution (ORS). In case of oral route failure, nasogastric tube enteral rehydration is as efficient as intra-venous rehydration and seems to lead to fewer adverse events. The primary objective was to describe rehydration strategies used in cases of AGE in pediatric emergency departments (PEDs) in Belgium, France, The Netherlands, and Switzerland. METHODS: An electronic survey describing a scenario in which a toddler had moderate dehydration caused by AGE was sent to physicians working in pediatric emergency departments. Analytical data were analyzed with descriptive statistics and Kruskal -Wallis Rank test. RESULTS: We analyzed 68 responses, distributed as follows: Belgium N = 10, France N = 37, The Netherlands N = 7, and Switzerland N = 14. Oral rehydration with ORS was the first line of treatment for 90% of the respondents. In case of first line treatment failure, intravenous rehydration was preferred by 95% of respondents from France, whereas nasogastric route was more likely to be used by those from Belgium (80%), The Netherlands (100%) and Switzerland (86%). Serum electrolyte measurements were more frequently prescribed in France (92%) and Belgium (80%) than in The Netherlands (43%) and Switzerland (29%). Racecadotril was more frequently used in France, and ondansetron was more frequently used in Switzerland. No respondent suggested routine use of antibiotics. CONCLUSION: We found variations in practices in terms of invasiveness and testing. Our study supports the need for further evaluation and implementation strategies of ESPGHAN/ESPID guidelines. We plan to extend the study throughout Europe with support of the Young ESPID Group.

Real-world effectiveness of nirsevimab immunisation against bronchiolitis in infants: a case-control study in Paris, France.

BACKGROUND: Respiratory syncytial virus (RSV) is the most common cause of bronchiolitis in infants. Nirsevimab, an RSV-neutralising monoclonal antibody, was approved for use in the EU in 2022, and a national immunisation campaign began in France in September, 2023. We aimed to assess the effectiveness of nirsevimab in reducing paediatric emergency department visits (and subsequent hospitalisations) for all-cause bronchiolitis and RSV-associated bronchiolitis. METHODS: In this case-control study in a paediatric emergency department in Paris, France, we included all infants aged 12 months or younger who attended the department between Oct 14, 2023, and Feb 29, 2024, and whose nirsevimab status was known. Infants were classed as cases if they had all-cause bronchiolitis; all other infants were classed as controls. The primary outcome was the effectiveness of nirsevimab against paediatric emergency department visits for all-cause bronchiolitis during the 2023-24 RSV season. Secondary outcomes were paediatric emergency department visits for RSV-associated bronchiolitis; hospitalisations for all-cause bronchiolitis, RSV-associated bronchiolitis, and severe RSV-associated bronchiolitis requiring supplemental oxygen or feeding by nasogastric tube; and severe RSV-associated bronchiolitis requiring admission to the paediatric intensive care unit. Effectiveness estimates were adjusted for age, week of paediatric emergency department visit, and sex. FINDINGS: Our study included 2786 infants, 864 with all-cause bronchiolitis (cases) and 1922 without bronchiolitis (controls). 178 (21%) of the 864 cases had received nirsevimab, and 305 (35%) cases were hospitalised for all-cause bronchiolitis. 200 (72%) of the 277 cases tested for RSV were positive, of whom 22 (11%) had received nirsevimab. 701 (36%) of 1922 infants in the control group had received nirsevimab. The effectiveness of nirsevimab against paediatric emergency department visits for all-cause bronchiolitis was 47% (95% CI 33-58). Nirsevimab effectiveness was 83% (71-90) against paediatric emergency department visits for RSV-associated bronchiolitis, 59% (42-71) against hospitalisations for all-cause bronchiolitis, 83% (72-90) against hospitalisations for RSV-associated bronchiolitis (91% [78-96] against those necessitating supplement oxygen and 88% [74-95] against those necessitating feeding via a nasogastric tube). Nirsevimab did not significantly reduce admissions to the paediatric intensive care unit (67% [95% CI -100 to 95]). INTERPRETATION: During the first French national immunisation campaign, a single dose of nirsevimab effectively reduced paediatric emergency department visits (both all-cause visits and visits related to RSV-associated bronchiolitis) and subsequent hospitalisations. FUNDING: None.

Association between pertactin-producing Bordetella pertussis and fulminant pertussis in infants: a multicentre study in France, 2008-2019.

OBJECTIVES: Virulence factors of the causative agent, Bordetella pertussis, may be involved in fulminant pertussis, the most severe form of whooping cough (pertussis) in infants. We aimed to assess the association between fulminant pertussis and the status of pertactin (PRN) production of B. pertussis clinical isolates. METHODS: Symptomatic infants aged <6 months with a positive B. pertussis culture from 2008-2019 were included. B. pertussis isolates and clinical data were collected from French hospital laboratories through the national pertussis surveillance network. Fulminant pertussis was defined as a case with a leukocyte count >40 × 109/L and at least one of the following criteria: respiratory failure, pulmonary hypertension, shock, or multiple organ failure. PRN production was assessed by western blotting. Baseline characteristics of infants and microbiological findings were compared between patients with and without fulminant pertussis. To identify patient and microbiological features associated with fulminant pertussis, a multivariable modified Poisson regression model was developed with confounders selected using a directed acyclic graph. RESULTS: We included 361 infants with pertussis (median age 63 days [interquartile range, 39-86]), of whom 32 (9%) progressed to fulminant pertussis. None of the mothers was vaccinated during pregnancy. Of the 361 implicated B. pertussis isolates, 294 (81%) produced PRN. Patients with fulminant pertussis were more often neonates (adjusted relative risk [aRR]: 3.62, 95% confidence interval [CI]: 1.76-7.44), infants with a history of prematurity (aRR: 7.08, 95% CI: 3.06-16.36), unvaccinated infants (aRR: 4.42, 95% CI: 1.02-19.24), and infants infected by PRN-producing isolates (aRR: 3.76, 95% CI: 1.02-13.83). DISCUSSION: PRN-producing B. pertussis was independently associated with an increased risk of fulminant pertussis. In a context where PRN-containing acellular pertussis vaccines favour the emergence of PRN-deficient isolates, our study suggests a positive role for such vaccines in driving the evolution of B. pertussis populations towards reduced virulence.

Preschool-age children maintain a distinct memory CD4+ T cell and memory B cell response after SARS-CoV-2 infection.

The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-reactive CD3+CD4+CD154+ T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4+ T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4+ T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2-reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.

Two atypical cases of Kingella kingae invasive infection with concomitant human rhinovirus infection.

We describe two atypical cases of Kingella kingae infection in children diagnosed by PCR, one case involving a soft tissue abscess and one case a femoral Brodie abscess. Both patients had concomitant human rhinovirus infection. K. kingae strains, isolated from an oropharyngeal swab, were characterized by multilocus sequence typing and rtxA sequencing.

Antimicrobial treatment of skin and soft tissue infections.

Bacterial skin infections are common in children, and frequently do not require systemic antibiotic therapy, particularly for superficial forms. In these cases, washing (with soap and water) and careful rinsing of the lesion are the key points of treatment. A semiotic analysis must precede any therapeutic decision to assess the appropriateness of antibiotic therapy, need for drainage (which may be spontaneous or surgical) and possible existence of symptoms related to toxin production, which are frequent signs of severity. The bacterial species most frequently implicated in children are Staphylococcus aureus and Streptococcus pyogenes. Given the low incidence of methicillin-resistant S. aureus in France (<10%), the first-line antibiotic treatment is amoxicillin-clavulanate, to which an anti-toxin treatment such as clindamycin may be added for patients with overt toxin signs.

Treatment of Resistant Gram-negative bacilli in children.

Resistance of Gram-negative bacteria to the most widely used antibiotics, particularly ß-lactams, is now considered as major public health problem. The main resistance mechanisms to ß-lactams in Enterobacterales are the production of extended spectrum ß-lactamases (ESBL) or carbapenemases, which hydrolyze virtually all ß-lactams. However, a substantial proportion of carbapenem-resistant Gram-negative bacilli do not produce carbapenemase but combine overproduction of a cephalosporinase and/or ESBL with very low penem hydrolysis and reduced outer membrane permeability. The arrival of new antibacterial agents active on some of these multidrug-resistant strains, such as new ß-lactam inhibitors, has marked a turning point in treatment and represents real progress. In-depth knowledge of resistance mechanisms is crucial to the choice of the most effective molecule, and their prescription requires close collaboration between microbiologists, infectious disease specialists and intensive care physicians. While these compounds are significantly more active against resistant strains than those previously available, their spectrum of activity does not cover all resistance mechanisms in Gram-negatives, nor in other bacterial species potentially involved in polymicrobial infections. The use of these new compounds does not alter antibiotic regimens in terms of duration and indication of combined antibiotic therapy, which remain very limited.

Antibiotic therapy for osteoarticular infections in 2023: Proposals from the Pediatric Infectious Pathology Group (GPIP).

Most osteoarticular infections (OAI) occur via the hematogenous route, affect children under 5 years of age old, and include osteomyelitis, septic arthritis, osteoarthritis and spondylodiscitis. Early diagnosis and prompt treatment are needed to avoid complications. Children with suspected OAI should be hospitalized at the start of therapy. Surgical drainage is indicated in patients with septic arthritis or periosteal abscess. Staphylococcus aureus is implicated in OAI in children at all ages; Kingella kingae is a very common causative pathogen in children from 6 months to 4 years old. The French Pediatric Infectious Disease Group recommends empirical antibiotic therapy with appropriate coverage against methicillin-sensitive S. aureus (MSSA) with high doses (150 mg/kg/d) of intravenous cefazolin. In most children presenting uncomplicated OAI with favorable outcome (disappearance of fever and pain), short intravenous antibiotic therapy during 3 days can be followed by oral therapy. In the absence of bacteriological identification, oral relay is carried out with the amoxicillin/clavulanate combination (80 mg/kg/d of amoxicillin) or cefalexin (150 mg/kg/d). If the bacterial species is identified, antibiotic therapy will be adapted to antibiotic susceptibility. The minimum total duration of antibiotic therapy should be 14 days for septic arthritis, 3 weeks for osteomyelitis and 4-6 weeks for OAI of the pelvis, spondylodiscitis and more severe OAI, and those evolving slowly under treatment or with an underlying medical condition (neonate, infant under 3 months of old, immunocompromised patients). Treatment of spondylodiscitis and severe OAI requires systematic orthopedic advice.