Host RNA Expression Signatures in Young Infants with Urinary Tract Infection: A Prospective Study.

Early diagnosis of infections in young infants remains a clinical challenge. Young infants are particularly vulnerable to infection, and it is often difficult to clinically distinguish between bacterial and viral infections. Urinary tract infection (UTI) is the most common bacterial infection in young infants, and the incidence of associated bacteremia has decreased in the recent decades. Host RNA expression signatures have shown great promise for distinguishing bacterial from viral infections in young infants. This prospective study included 121 young infants admitted to four pediatric emergency care departments in the capital region of Denmark due to symptoms of infection. We collected whole blood samples and performed differential gene expression analysis. Further, we tested the classification performance of a two-gene host RNA expression signature approaching clinical implementation. Several genes were differentially expressed between young infants with UTI without bacteremia and viral infection. However, limited immunological response was detected in UTI without bacteremia compared to a more pronounced response in viral infection. The performance of the two-gene signature was limited, especially in cases of UTI without bloodstream involvement. Our results indicate a need for further investigation and consideration of UTI in young infants before implementing host RNA expression signatures in clinical practice.

NON-pharmacological Approach Less Invasive Surfactant Administration (NONA-LISA) trial: protocol for a randomised controlled trial.

INTRODUCTION: Using pre-procedure analgesia with the risk of apnoea may complicate the Less Invasive Surfactant Administration (LISA) procedure or reduce the effect of LISA. METHODS: The NONA-LISA trial (ClinicalTrials.gov, NCT05609877) is a multicentre, blinded, randomised controlled trial aiming at including 324 infants born before 30 gestational weeks, meeting the criteria for surfactant treatment by LISA. Infants will be randomised to LISA after administration of fentanyl 0.5-1 mcg/kg intravenously (fentanyl group) or isotonic saline solution intravenously (saline group). All infants will receive standardised non-pharmacological comfort care before and during the LISA procedure. Additional analgesics will be provided at the clinician's discretion. The primary outcome is the need for invasive ventilation, meaning mechanical or manual ventilation via an endotracheal tube, for at least 30 min (cumulated) within 24 h of the procedure. Secondary outcomes include the modified COMFORTneo score during the procedure, bronchopulmonary dysplasia at 36 weeks, and mortality at 36 weeks. DISCUSSION: The NONA-LISA trial has the potential to provide evidence for a standardised approach to relief from discomfort in preterm infants during LISA and to reduce invasive ventilation. The results may affect future clinical practice. IMPACT: Pre-procedure analgesia is associated with apnoea and may complicate procedures that rely on regular spontaneous breathing, such as Less Invasive Surfactant Administration (LISA). This randomised controlled trial addresses the effect of analgesic premedication in LISA by comparing fentanyl with a placebo (isotonic saline) in infants undergoing the LISA procedure. All infants will receive standardised non-pharmacological comfort. The NONA-LISA trial has the potential to provide evidence for a standardised approach to relief from discomfort or pain in preterm infants during LISA and to reduce invasive ventilation. The results may affect future clinical practice regarding analgesic treatment associated with the LISA procedure.

Individualised versus standard duration of antibiotic therapy in children with acute uncomplicated febrile urinary tract infection: a study protocol and statistical analysis plan for a multicentre randomised clinical trial.

INTRODUCTION: Febrile urinary tract infection is one of the most common bacterial infections in children. Currently, recommended antibiotic duration is 10 days. However, recent evidence suggests that 90%-95% of children with febrile urinary tract infections are afebrile and clinically improved 48-72 hours after treatment initiation. Accordingly, individualised duration of antibiotic therapy, according to the recovery time, might be more beneficial than current recommendations, but no evidence exists. METHODS AND ANALYSIS: An open-label randomised clinical trial equally randomising children aged 3 months to 12 years from eight Danish paediatric departments with uncomplicated febrile (≥38°C) urinary tract infection to either individualised or standard duration of antibiotic therapy. Children allocated to individualised duration of antibiotic therapy will terminate antibiotic therapy 3 days after clinical improvement with no fever, flank pain or dysuria. Children allocated to standard duration will receive 10 days of antibiotic therapy. Co-primary outcomes are non-inferiority for recurrent urinary tract infection or death within 28 days after the end of treatment (non-inferiority margin 7.5 percentage points) and superiority for the number of days with antibiotic therapy within 28 days after treatment initiation. Seven other outcomes will also be assessed. A total of 408 participants are needed to detect non-inferiority (one-sided alpha 2.5%; beta 80%). ETHICS AND DISSEMINATION: This trial has been approved by the Ethics Committee (H-21057310) and the Data Protection Agency (P-2022-68) in Denmark. Regardless of the trial's findings (whether positive, negative or inconclusive), the results will be compiled into one or more manuscripts for publication in international peer-reviewed scientific journals and presented at conferences. TRIAL REGISTRATION NUMBER: NCT05301023.

[Herpes simplex virus infection in newborns].

Neonatal herpes simplex disease (HSV) is a rare but life-threatening infection associated with high rates of morbidity and mortality. Recent studies indicate that the incidence rate has continued to rise over the past decades, while the mortality remains unchanged. Early clinical suspicion of HSV and parenteral antiviral treatment of acute disease is essential for the prognosis. The subsequent use of suppressive therapy with oral acyclovir has further enhanced the long-term prognosis. This review presents evidence of risk factors, clinical presentation, prevention, and management of HSV in newborns.