Therapeutic Options and Outcomes for the Treatment of Children with Gram-Positive Bacteria with Resistances of Concern: A Systematic Review.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci (MR-CoNS), and vancomycin-resistant Enterococci (VRE) are increasing worldwide and represent a threat for the limited treatment options in pediatric patients and neonates compared to adults. Recommendations in pediatrics are mainly extrapolated from adults' studies. METHODS: A literature search for the treatment of these pathogens in children (<18 years old) was conducted in Embase, MEDLINE, and Cochrane Library. Studies reporting data on single-patient-level outcomes related to a specific antibiotic treatment for multidrug resistant (MDR) Gram-positive bacterial infection in children were included. Studies reporting data from adults and children were included if single-pediatric-level information could be identified (PROSPERO registration: CRD42022383867). RESULTS: The search identified 11,740 studies (since January 2000), of which 48 fulfilled both the inclusion and the exclusion criteria and were included in the analysis: 29 for MRSA, 20 for VRE, and seven for MR-CoNS. Most studies were retrospective studies. Vancomycin was mainly used as a comparator, while linezolid and daptomycin were the most studied antimicrobials showing good efficacy. CONCLUSIONS: Linezolid showed a safety and efficacy profile in a neonatal setting; daptomycin is increasingly used for MRSA, but the evidence is scarce for VRE.

Early Treatments of Fragile Children with COVID-19-Results of CLEVER (Children COVID Early Treatment), a Retrospective, Observational Study.

(1) Background: SARS-CoV-2 infection is notably mild in children, though comorbidities may increase the risk of hospitalization and may represent a risk for increased disease severity. There is an urgent need for targeted therapies with an acceptable efficacy and safety profile. To date, most of the medicines for COVID-19-specific treatment are prescribed off-label for children due to a lack of clinical trials and consequent evidence in this population. (2) Methods: This was a retrospective, observational study investigating the safety of treatments for the prevention of severe COVID-19 in fragile pediatric patients who received monoclonal antibodies and antivirals for mild-to-moderate symptoms between December 2021 and July 2022. (3) Results: Thirty-two patients were included. Monoclonal antibodies were prescribed to 62%, intravenous antivirals to 22%, and oral antivirals to 16% of children. Sotrovimab was the most frequently prescribed drug among monoclonal antibodies and overall (59%). The second most prescribed drug was remdesivir (22%). No severe adverse drug reaction was reported. There was no progression to severe disease and no death cases due to COVID-19 or drug administration. At drug-type stratification, resolution of symptoms and swab positivity time showed no difference between the two groups at 7 and 28 days. Off-label prescriptions were 84% overall, and in similar proportions between the two groups. (4) Conclusions: in this small sample, antivirals seemed safe and showed no differences in efficacy as compared to MAbs for the early treatment of COVID-19 in fragile children, thus representing a valuable choice, even when administered off-label.

Clinical features of COVID-19 in Italian outpatient children and adolescents during Parental, Delta, and Omicron waves: a prospective, observational, cohort study.

Introduction: COVID-19 features changed with the Omicron variant of SARS-CoV-2 in adults. This study aims to describe COVID-19 symptoms in children and adolescents during the Parental, Delta, and Omicron eras. Methods: A single-centre, prospective observational study was conducted on individuals aged 0-20 years attending the University Hospital of Padua (Italy) from April 2020 to December 2022. COVID-19 cases were defined by positive SARS-CoV-2 molecular detection and/or serology; patient/family symptoms and virological positivity were considered to determine the infection onset. Variables were summarized and compared using appropriate tests of descriptive statistics. Results: A total of 509 cases [46% female, median age eight years (IQR: 4-12)] were studied. Three-hundred-eighty-seven (76%), 52 (10%), and 70 (14%) subjects experienced COVID-19 during the Parental, Delta, and Omicron waves, respectively. All subjects developed an asymptomatic/mild COVID-19. Overall, the most frequent symptoms were fever (47%) and rhinitis (21%), which showed a significant increasing incidence from the Parental to Omicron waves (p < 0.001). Conversely, diarrhea was most common during the pre-Omicron eras (p = 0.03). Stratifying symptoms according to the age group, fever, rhinitis, and skin rashes were observed more frequently among infants/toddlers; conversely, fatigue was more common in children older than five years. The duration of symptoms was similar across different SARS-CoV-2 variants of concern (VOCs); conversely, the number of symptoms varied according to the age group (p < 0.0001). Discussion: This study showed differences in COVID-19 clinical presentation among infants, children, and adolescents and confirmed Omicron infection is more likely to be associated with upper respiratory symptoms. However, further population-based studies are needed to support these findings. In addition, active surveillance will play a crucial role in assessing the disease severity of future VOCs.

Enteral Linezolid as an Effective Option to Treat an Extremely Preterm Infant with Bacillus cereus Sepsis.

We report the safe and effective use of oral linezolid for treatment of Bacillus cereus sepsis in an extremely preterm neonate, previously fed with human donor milk, in which a Brevibacillus sp. was eventually found. Due to several predisposing factors, premature, very low birth weight newborns are extremely vulnerable to invasive infections by environmental pathogens. After vancomycin microbiologic treatment failure (despite adequate blood concentrations and clinical response), linezolid was chosen for its optimal enteral absorption and bioavailability, also after exhaustion of peripheral venous heritage. No adverse events were recorded, with clinical cure. We reviewed the literature on B. cereus infections in newborns, together with the available evidence on the use of linezolid in similar contexts.

Early Use of Sotrovimab in Children: A Case Report of an 11-Year-Old Kidney Transplant Recipient Infected with SARS-CoV-2.

BACKGROUND: The use of virus-neutralizing monoclonal antibodies has been approved in fragile populations, including kidney transplant recipients, who are at risk of developing severe COVID-19. Sotrovimab is the only currently available anti-SARS-CoV-2 neutralizing monoclonal antibody with activity against the new Omicron variant of concern. While sotrovimab has been approved in adolescents and adults, studies regarding its efficacy and safety in children aged less than 12 years old and weighing less than 40 kg are still lacking. Here, we report a first case of a child, who was treated early with sotrovimab after a kidney transplant. CASE REPORT: At the end of January 2022, a 11-year-old male child underwent a deceased-donor kidney transplant and became infected with SARS-CoV-2 during the first day after surgery. Due to the increased risk of developing severe COVID-19, based on the predominance of Omicron and the patient's renal function, the child was treated with sotrovimab. The clinical course was successful and no adverse reactions were reported. CONCLUSIONS: For the first time, we report the well-tolerated use of sotrovimab in children under 12 years old. As the pandemic affects children across the globe, urgent data on sotrovimab dosing in children with a higher risk of developing severe COVID-19 are needed.