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.

Diabetic ketoacidosis and severe hypertriglyceridaemia in a child.

Diabetic ketoacidosis (DKA) in children with severe hypertriglyceridaemia (S-HTG) is infrequent. This case report presents a seven-year-old girl without a family history of dyslipidaemia with moderate DKA, lipaemic plasma, retinal lipaemia, and P-triglyceride 185 mmol/l. The course was uneventful on standard treatment and lipids normalized. She had abdominal pain but no biochemical or ultrasound evidence of pancreatitis. S-HTG affected laboratory analysis; CO2 could not be analyzed, and there was haemolysis and uncertain electrolyte results with P-Na+ 125 mmol/l, i.e. pseudo hyponatraemia, despite ultracentrifugation.

[Tubulointerstitial nephritis and uveitis syndrome].

Tubulointerstitial nephritis and uveitis (TINU) syndrome in children is an uncommon, underreported condition. Onset of renal and ocular symptoms is often not simultaneous with nephritis which may precede uveitis by several months. A variable treatment response and a propensity for relapse characterize the syndrome. This is a case report of a previously healthy 14-year-old boy with TINU syndrome, emphasizing the need for long-term interdisciplinary treatment and monitoring. Also, the importance of repetitive screening of patients with uveitis for renal disease and ophthalmological evaluation of children with nephritis is emphasized.

Population-based Incidence of Myopericarditis After COVID-19 Vaccination in Danish Adolescents.

In this prospective nationwide multicenter study from Denmark, myopericarditis after Pfizer-BioNTech mRNA COVID-19 vaccination was identified in 13 males and 2 females between May 15 and September 15, 2021, among 133,477 vaccinated males and 127,857 vaccinated females 12-17 years of age, equaling 97 males and 16 females per million. In conclusion, the incidence of myopericarditis after COVID-19 vaccination among males appears higher than reports from the United States.

[Familial hypomagnesaemia with secondary hypocalcaemia as a cause of seizures in children].

This case report presents a three-month-old girl, previously healthy, who was admitted to the hospital due to a cyanotic episode during breastfeeding. The episode was initially interpreted as aspiration. She had recurrent generalised seizures, and blood tests revealed hypomagnesaemia and hypocalcaemia. The electrolyte abnormalities were corrected by intravenous magnesium with subsequent normalisation of the calcium level. Genetic testing discovered a deletion in the TRPM6, which is associated with familial hypomagne-s-aemia with secondary hypocalcaemia. It is important to identify electrolyte disturbances in infants with afebrile seizures.

Tubulointerstitial nephritis and uveitis (TINU) syndrome: a case report and review of the literature.

PURPOSE: We aim to describe the first case of tubulointerstitial nephritis and uveitis (TINU) syndrome reported in Scandinavia and to underline the importance of the syndrome, which should be better known among ophthalmologists. METHODS: We report an 11-year-old boy who was admitted to hospital because of general fatigue and weight loss. Blood tests showed renal insufficiency and a renal biopsy revealed acute tubulointerstitial nephritis. One week after admission the patient developed transitory blurred vision and flickering shadows in the left eye. Slit-lamp examination revealed bilateral anterior non-granulomatous uveitis and TINU syndrome was diagnosed. RESULTS: Because of renal insufficiency the patient was treated with systemic prednisone 50 mg/day for 3 weeks. Evolution was favourable, and prednisone was tapered over 10 weeks. Uveitis was treated with topical steroid with good effect. The only complication after 18 months of follow-up was transitory cushingoid aspect. CONCLUSIONS: Tubulointerstitial nephritis and uveitis syndrome is a rare syndrome that is probably underdiagnosed in clinical practice. Co-operation between ophthalmologists and nephrologists/paediatricians is crucial for early diagnosis and instigation of treatment. Uveitis may occur before tubulointerstitial nephritis or the renal symptoms may be so mild that the patient is unaware of them. Therefore, ophthalmologists play an important role in the initial discovery of patients with TINU syndrome. Tubulointerstitial nephritis tends to be self-limiting, whereas uveitis tends to relapse and recurrences tend to be more severe than the initial uveitis. Therefore, the patient must be ophthalmologically monitored very carefully.

[Diagnosis of meningococcal sepsis by real-time polymerase chain reaction]. / Meningokoksepsis diagnosticeret ved realtids-polymerasekaedereaktion.

Approximately 100 cases of meningococcal disease are reported annually in Denmark; 90% of these cases are confirmed by culture and serological methods. Real-time PCR was introduced in Denmark in 2005 as a diagnostic tool for meningococcal disease. We hereby report the first notified case of meningococcal sepsis in Denmark where real-time PCR was the primary positive microbiological result.

[Prenatal diagnosed hydronephrosis and other urological anomalies]. / Praenatalt diagnosticeret hydronefrose og andre urologiske anomalier.

By renal ultrasound examination, urological anomalies may be demonstrated in 1-2% of fetuses and in about 0.5% of newborns. Boys have about twice the frequency of girls. Surgical treatment is indicated in about one fourth of these urological anomalies. If all pregnant women in Denmark were to have fetal ultrasound examination of the kidneys and the urinary tract, about 70 children would be born each year with a prenatally diagnosed urological anomaly for which surgical procedure is or will be indicated. This paper provides Danish guidelines for prenatal diagnosis, follow-up and intervention in cases of urological anomalies and guidelines for post-natal diagnosis, follow-up and treatment of these anomalies, especially hydronephrosis.