Type I Interferon in Children with Viral or Bacterial Infections.

BACKGROUND: Fever is one of the leading causes of consultation in the pediatric emergency department for patients under the age of 3 years. Distinguishing between bacterial and viral infections etiologies in febrile patients remains challenging. We hypothesized that specific host biomarkers for viral infections, such as type I-interferon (IFN), could help clinicians' decisions and limit antibiotic overuse. METHODS: Paxgene tubes and serum were collected from febrile children (n = 101), age from 7 days to 36 months, with proven viral or bacterial infections, being treated at pediatric emergency departments in France. We assessed the performance of an IFN signature, which was based on quantification of expression of IFN-stimulated genes using the Nanostring® technology and plasma IFN-α quantified by digital ELISA technology. RESULTS: Serum concentrations of IFN-α were below the quantification threshold (30 fg/mL) for 2% (1/46) of children with proven viral infections and for 71% (39/55) of children with bacterial infections (P < 0.001). IFN-α concentrations and IFN score were significantly higher in viral compared to bacterial infection (P < 0.001). There was a strong correlation between serum IFN-α concentrations and IFN score (p-pearson = 0.83). Both serum IFN-α concentration and IFN score robustly discriminated (Area Under the Curve >0.91 for both) between viral and bacterial infection in febrile children, compared to C-reactive protein (0.83). CONCLUSIONS: IFN-α is increased in blood of febrile infants with viral infections. The discriminative performance of IFN-α femtomolar concentrations as well as blood transcriptional signatures could show a diagnostic benefit and potentially limit antibiotic overuse. CLINICAL TRIALS REGISTRATION: clinicaltrials.gov (NCT03163628).

Percutaneous guided biopsy for diagnosing suspected primary malignant bone tumors in pediatric patients: a safe, accurate, and cost-saving procedure.

BACKGROUND: Percutaneous biopsy is the reference diagnostic procedure for adult musculoskeletal tumors. Its place in pediatrics is controversial and open biopsy remains recommended. OBJECTIVE: To assess diagnostic performance and feasibility of percutaneous biopsy performed on children and young adults for suspected malignant bone tumors. MATERIALS AND METHODS: We conducted a 5-year retrospective study including patients ≤21 years who underwent a bone biopsy for a suspected malignant bone tumor. We assessed diagnostic yield (percentage of analyzable biopsies), accuracy (percentage of accurate diagnoses among all analyzable biopsies) and efficacy (percentage of accurate diagnoses among all biopsies), costs, anesthetic requirements and sample availability for biomedical research. Patients diagnosed with an open biopsy were used to compare diagnostic performances, anesthetic requirements and costs. RESULTS: We included 90 percutaneous and 27 open biopsies in 117 patients. For percutaneous biopsy, diagnostic yield was 95.5% (95% confidence interval [CI] 88.8-98.7%), accuracy was 96.2% (95% CI 86.8-99.5%) and efficacy was 89.3% (95% CI 78.1-96.0%). There was no statistical difference with open biopsy (Fisher exact test, P > 0.05). Mean costs were reduced with percutaneous biopsy: €1,937 (standard deviation [SD] €2,408) versus €6,362 (SD €5,033; Mann-Whitney, P < 0.0001). Thirty-two of the 48 (67%) patients included in clinical trials and diagnosed with percutaneous biopsy had suitable samples for ancillary analyses. CONCLUSION: Percutaneous biopsy is a valid alternative to open biopsy for diagnosing pediatric and young adult primary malignant bone tumors.

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.

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.

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.

Performance Evaluation of Host Biomarker Combinations for the Diagnosis of Serious Bacterial Infection in Young Febrile Children: A Double-Blind, Multicentre, Observational Study.

The diagnosis of serious bacterial infection (SBI) in young febrile children remains challenging. This prospective, multicentre, observational study aimed to identify new protein marker combinations that can differentiate a bacterial infection from a viral infection in 983 children, aged 7 days-36 months, presenting with a suspected SBI at three French paediatric emergency departments. The blood levels of seven protein markers (CRP, PCT, IL-6, NGAL, MxA, TRAIL, IP-10) were measured at enrolment. The patients received the standard of care, blinded to the biomarker results. An independent adjudication committee assigned a bacterial vs. viral infection diagnosis based on clinical data, blinded to the biomarker results. Computational modelling was applied to the blood levels of the biomarkers using independent training and validation cohorts. Model performances (area under the curve (AUC), positive and negative likelihood ratios (LR+ and LR-)) were calculated and compared to those of the routine biomarkers CRP and PCT. The targeted performance for added value over CRP or PCT was LR+ ≥ 5.67 and LR- ≤ 0.5. Out of 652 analysed patients, several marker combinations outperformed CRP and PCT, although none achieved the targeted performance criteria in the 7 days-36 months population. The models seemed to perform better in younger (7-91 day-old) patients, with the CRP/MxA/TRAIL combination performing best (AUC 0.895, LR+ 10.46, LR- 0.16). Although computational modelling using combinations of bacterial- and viral-induced host-protein markers is promising, further optimisation is necessary to improve SBI diagnosis in young febrile children.

Septic Arthritis of Facet Joint in Children: A Systematic Review and a 10-year Consecutive Case Series.

BACKGROUND: Due to the low resolution of historical imaging technologies, descriptions of Septic Arthritis of Facet Joint (SAFJ) in children are scarce, though severe cases are known. We first aimed to estimate the incidence rate of SAFJ in children; we further aimed to specify SAFJ clinical, imaging and laboratory findings, and identify avenues for appropriate management. METHODS: A 10-year consecutive SAFJ case series using our imaging center database combined with a 50-year systematic review of literature cases. RESULTS: The mean ± SD incidence of pediatric SAFJ was 0.23 ± 0.4/100,000 children-years. The key symptoms were potty refusal (in toddlers) or painful sitting (78%) and lateralized signs (paravertebral tenderness and/or swelling, 88%). SAFJ diagnosis and extension were obtained using magnetic resonance imaging (MRI) (94%), and found an epidural extension in 8/16 cases. The mean duration of antibiotic treatment was 5.1 weeks. The compliance with guidelines was 79% for empiric and 62% for targeted antibiotic therapies. CONCLUSIONS: SAFJ incidence in children is much greater than expected from the literature. Half of cases were complicated by an epidural infection. Simple clinical symptoms detected as early as the bedside allow a strong suspicion of SAFJ, justifying the use of a first-line MRI to confirm the diagnosis and precisely describe the extension. Focusing on simple clinical signs is key to justify the transfer of a child or the shortening of the delay to obtain an MRI. However, as MRI availability increases in most Western countries, and the capacity for diagnosis increases, the awareness of SAFJ must be spread to avoid missed cases.