Pediatric Infectious Disease Journal最新文献

Background: Sisunatovir is an investigational respiratory syncytial virus (RSV) antiviral that was effective in an adult human viral challenge study.

Methods: In 2 multicenter studies, safety and pharmacokinetics of sisunatovir were evaluated in hospitalized individuals 1 month to 36 months of age (Study 1) and outpatient and hospitalized individuals 1 day to 60 months of age (Study 2) with RSV lower respiratory tract infection (RSV-LRTI). In Study 1 Part A, participants received single sisunatovir doses; in Part B, participants received placebo or multiple ascending sisunatovir doses every 12 hours for 5 days. In Study 2, participants received weight-based sisunatovir dosing or placebo every 12 hours for 5 days.

Results: In Study 1 Part A, 19 participants received sisunatovir; 31 in Part B received sisunatovir (n = 22) or placebo (n = 9). Adverse events (AEs) were reported by 11 (57.9%) and 12 (38.7%) participants in Parts A and B, respectively. In Study 2, 10 participants received sisunatovir (n = 6) or placebo (n = 4). No treatment-related serious AEs were reported; all AEs were mild or moderate. In Study 1 Part A 12 hours post-dose, mean sisunatovir concentrations were within safety margins. In Part B, at the highest dose assessed for each group, steady-state trough concentrations surpassed those effective in the adult challenge study.

Conclusions: In children with RSV-LRTI, sisunatovir was safe and well tolerated. The pediatric multiple-dose regimen achieved plasma concentrations effective at reducing viral load and symptoms in an adult challenge study; however, further studies are needed to identify doses providing comparable exposure across pediatric populations.

Clinicaltrialsgov registration number: NCT04225897 (registered December 11, 2019); NCT06102174 (registered October 6, 2023).

Background: Human metapneumovirus (hMPV) is a significant respiratory pathogen in infants and young children. Although most infections present as nonsevere cases in outpatient settings, severe courses can lead to hospitalization. Few potential risk factors for hospitalization have already been identified, but studies comparing the clinical presentation of children with hMPV in inpatient versus outpatient settings are lacking.

Methods: This retrospective analysis used data from the Pediatric Airway Pathogen Incidence study, a multicenter surveillance study of lower respiratory tract infections, conducted in Germany during winter seasons 2021/22 and 2022/23 (weeks 40-17 each season). We compared 102 hospitalized and 114 outpatient pediatric cases with laboratory-confirmed hMPV infection after excluding coinfections with respiratory syncytial virus. Detailed clinical and demographic data were collected.

Results: Hospitalized patients were significantly younger (median age 9 vs. 14 months, P = 0.003) than outpatients. Prematurity was notably higher in severe cases (25% vs. 6.2%, P < 0.001), and extreme prematurity (gestational age <28 weeks) was present only in hospitalized patients. Hospitalized cases were independently associated with a history of recurrent wheezing, but not with neonatal invasive and noninvasive respiratory support, inhalative steroids and bronchopulmonary dysplasia. On clinical examination, hospitalized children more often exhibited wheezing, crackles, tachypnea, hypoxemia and reduced fluid intake. Hypoxemia in hMPV was independently associated with gestational age at birth, but not with age at diagnosis.

Conclusion: The clinical presentation of hMPV in hospitalized young children differed from that observed in outpatient settings. We identified multiple factors that were independently associated with hMPV-related hospitalization.

Background: Routine surveillance for vancomycin-resistant enterococci (VRE) colonization remains the standard practice in many intensive care units. However, in high-acuity pediatric intensive care units (PICUs), where clinical VRE infections are uncommon, universal screening may impose substantial financial and operational burdens with uncertain clinical benefits. This study evaluates the necessity and value of universal VRE surveillance by describing the clinical characteristics and risk profiles of asymptomatic VRE-colonized patients in a newly established, high-acuity, 54-bed PICU.

Methods: This single-center, retrospective cohort study included all patients with positive admission or weekly rectal VRE screening cultures between October 2023 and October 2024. Demographic, clinical, microbiologic (including species identification) and outcome variables were analyzed.

Results: Among 1270 PICU admissions, 74 patients (5.8%) were colonized with VRE; 42 (56.8%) were positive on admission and 32 (43.2%) acquired colonization during hospitalization. Enterococcus faecium was the predominant species (97.3%). Despite frequent exposure to recognized risk factors, including central venous catheters (79.7%), urinary catheters (77.0%), prolonged PICU stays and carbapenem exposure (62.2%), no patient developed a clinical VRE infection.

Conclusions: In this high-acuity PICU with robust infection prevention infrastructure, VRE colonization, including colonization with high-risk E. faecium strains, did not progress to clinical infection. These findings suggest that in high-acuity PICUs with established infection control excellence, the clinical yield of universal VRE screening may be marginal compared with its operational costs, supporting a transition toward targeted, risk-based surveillance.

Background: Human rhinovirus is one of the leading causes of pediatric respiratory infections worldwide. Its circulation patterns have shown notable changes in recent years. This study aimed to compare the epidemiologic, clinical and laboratory characteristics of rhinovirus infections and coinfections in 2 consecutive periods to identify shifts in age distribution, symptom patterns, healthcare utilization and pathogen codetection among pediatric patients.

Methods: A retrospective analysis was conducted at a tertiary pediatric center and included all children aged 0-18 years with laboratory-confirmed rhinovirus infection between December 2023 and October 2025. Two consecutive 11-month periods were compared: December 2023-October 2024 (Period 1) and December 2024-October 2025 (Period 2). Demographic and laboratory parameters were recorded.

Results: A total of 572 children with rhinovirus-positive samples were evaluated. The number of cases increased 2.9-fold in December 2024-October 2025 (Period 2) (from 141 to 431; 0.42 vs. 1.22 cases/day), while age and sex distributions remained similar. Children under 6 years represented the most detections, and the proportions of 0-2-year-old children were similar in both periods. Fever, cough and rhinorrhea were significantly less frequent in Period 2. Chest X-ray use increased overall (34.8%-49.7%) but remained unchanged among hospitalized patients. Hospitalization rates were comparable, and antibiotic use declined (60.0%-48.9%). Multivariable analysis showed that neither hospitalization nor antibiotic exposure predicted period assignment. Coinfections increased from 3.5% to 10.2%, though severe outcomes remained rare.

Conclusions: Human rhinovirus cases nearly tripled across 2 seasons, yet clinical severity did not increase. Fever, cough and rhinorrhea declined, antibiotic use decreased and hospitalization remained stable. Coinfections became more frequent but did not affect outcomes. These observations suggest that rhinovirus circulation is expanding with a shift toward milder, community-managed illness.

Twice-daily dosing of Dolutegravir is approved for adults with HIV and integrase strand transfer inhibitor resistance, but not for children. Population pharmacokinetic modeling and simulations identified a weight-tiered twice-daily dose for children, predicted to yield dolutegravir exposures within the therapeutic window and provide similar efficacy and safety as seen in adults with HIV-1 and first-generation integrase strand transfer inhibitor resistance.