Oral versus intravenous empirical antibiotics in children and adolescents with uncomplicated bone and joint infections: a nationwide, randomised, controlled, non-inferiority trial in Denmark.

BACKGROUND: Bone and joint infections (BJIs) are treated with intravenous antibiotics, which are burdensome and costly. No randomised controlled studies have compared if initial oral antibiotics are as effective as intravenous therapy. We aimed to investigate the efficacy and safety of initial oral antibiotics compared with initial intravenous antibiotics followed by oral antibiotics in children and adolescents with uncomplicated BJIs. METHODS: From Sept 15, 2020, to June 30, 2023, this nationwide, randomised, non-inferiority trial included patients aged 3 months to 17 years with BJIs who presented to one of the 18 paediatric hospital departments in Denmark. Exclusion criteria were severe infection (ie, septic shock, the need for acute surgery, or substantial soft tissue involvement), prosthetic material, comorbidity, previous BJIs, or antibiotic therapy for longer than 24 h before inclusion. Patients were randomly assigned (1:1), stratified by C-reactive protein concentration (<35 mg/L vs ≥35 mg/L), to initially receive either high-dose oral antibiotics or intravenous ceftriaxone (100 mg/kg per day in one dose). High-dose oral antibiotics were coformulated amoxicillin (100 mg/kg per day) and clavulanic acid (12·5 mg/kg per day) in three doses for patients younger than 5 years or dicloxacillin (200 mg/kg per day) in four doses for patients aged 5 years or older. After a minimum of 3 days, and upon clinical improvement and decrease in C-reactive protein, patients in both groups received oral antibiotics in standard doses. The primary outcome was sequelae after 6 months in patients with BJIs, defined as any atypical mobility or function of the affected bone or joint, assessed blindly, in all randomised patients who were not terminated early due to an alternative diagnosis (ie, not BJI) and who attended the primary outcome assessment. A risk difference in sequelae after 6 months of less than 5% implied non-inferiority of the oral treatment. Safety outcomes were serious complications, the need for surgery after initiation of antibiotics, and treatment-related adverse events in the as-randomised population. This trial was registered with ClinicalTrials.gov, NCT04563325. FINDINGS: 248 children and adolescents with suspected BJIs were randomly assigned to initial oral antibiotics (n=123) or initial intravenous antibiotics (n=125). After exclusion of patients without BJIs (n=54) or consent withdrawal (n=2), 101 patients randomised to oral treatment and 91 patients randomised to intravenous treatment were included. Ten patients did not attend the primary outcome evaluation. Sequelae after 6 months occurred in none of 98 patients with BJIs in the oral group and none of 84 patients with BJIs in the intravenous group (risk difference 0, one-sided 97·5% CI 0·0 to 3·8, pnon-inferiority=0·012). Surgery after randomisation was done in 12 (9·8%) of 123 patients in the oral group compared with seven (5·6%) of 125 patients in the intravenous group (risk difference 4·2%, 95% CI -2·7 to 11·5). We observed no serious complications. Rates of adverse events were similar across both treatment groups. INTERPRETATION: In children and adolescents with uncomplicated BJIs, initial oral antibiotic treatment was non-inferior to initial intravenous antibiotics followed by oral therapy. The results are promising for oral treatment of uncomplicated BJIs, precluding the need for intravenous catheters and aligning with the principles of antimicrobial stewardship. FUNDING: Innovation Fund Denmark and Rigshospitalets Forskningsfond.

Prevalence of SARS-CoV-2-Antibodies in Danish Children and Adults.

In Denmark, severe acute respiratory syndrome coronavirus 2 antibodies were assessed in a cross-sectional study among 1033 children visiting pediatric departments and 750 blood donors in June 2020, using a point-of-care test. Antibodies were detected in 17 children (1.6%) and 15 blood donors (2.0%) (P = 0.58). In conclusion, children and adults were infected to a similar low degree.

[Subglottic haemangioma]. / Subglottisk hæmangiom.

Subglottic haemangioma (SGH) is the rare condition of an infantile haemangioma in the subglottic space. The diagnostics is complicated due to the clinical symptoms mimicking pseudocroup, and difficulties in visualization of the subglottic space. A two-month-old girl with a cycle of repeated hospitalizations due to recurrent and progressive croupal cough and stridor was diagnosed with SGH by laryngoscopy and initiated propranolol treatment with effect after 48 hours. SGH is rare but should be kept in mind in infants with recurrent croupal cough and stridor.

Heart rate variability in children with exercise-induced idiopathic ventricular arrhythmias.

Ventricular arrhythmias (VAs) are common pediatric rhythm disorders requiring comprehensive laboratory evaluation. Although usually idiopathic, implying a benign character and favorable prognosis, the initial clinical approach is still not established in all cases. Considering their prognostic significance, exercise-induced (precipitated or aggravated) VAs usually require additional diagnostics, treatment, and follow-up. A number of reports have presented experimental and clinical evidence that increased sympathetic activity can initiate, or at least facilitate, VAs. Recent data highlight the relationship between exercise-induced idiopathic VAs (IVAs) and the long-term risk of cardiovascular death. The aim of this study was to assess the utility of heart rate variability (HRV) analysis as a noninvasive method for estimating autonomic nervous activity in children with exercise induced IVAs. The study included 42 children with IVAs, who were divided into two groups: children with exercise induced (precipitated or aggravated) IVAs and children with exercised-suppressed IVAs. Time-domain HRV parameters were analyzed from 24-h ambulatory electrocardiography recordings, and the majority of children underwent an exercise stress test using the McMaster protocol. The results of this study showed no significant changes in parasympathetic index, i.e., the square root of the mean of the sum of the squares of the differences between adjacent NN intervals (the length between two successive heartbeats) between the groups examined. On the other hand, we observed diminished time-domain values for the standard deviation of all adjacent NN intervals, as well as diminished time-domain values for standard deviation of the averages of NN intervals in all 5-min segments in the group of children with exercise-induced IVAs, implicating increased sympathetic activity in such individuals. HRV analysis could be a helpful diagnostic method, giving useful information regarding cardiac autonomic control in some children with exercise-induced IVAs.