Journal of the Pediatric Infectious Diseases Society最新文献

Background: Critically ill pediatric patients admitted to the pediatric intensive care unit (PICU) are highly vulnerable to infections, including invasive fungal diseases and antifungal agents are frequently prescribed. Little is known about antifungal usage in PICUs across Europe.

Methods: A multinational 3-month weekly point-prevalence study for measuring antifungal drug use was organized. Eigtheen PICUs (16 hospitals) in 10 countries in the European region participated. All patients hospitalized in the participating PICUs and receiving systemic antifungals were included. Information about ward demographics was collected once; weekly ward and patient data were collected prospectively for the 12-week study period and entered in REDCap database.

Results: Among 18 PICUs, 8 (44%) followed prophylactic practices for targeted group of patients, 7/18 (39%) had an antifungal stewardship program and the majority (16/18, 89%) had the capacity of biomarker utilization (16/16 galactomannan, 13/16 beta-D-glucan, and 9/16 pan-fungal PCR). One hundred one courses in equal number of patients were recorded; 14 for patients aged <3 month, 87 for patients ≥3 month. Malignancy was the most common underlying condition among patients aged ≥3 month (29%) followed by surgery/trauma (25%), whereas all patients <3 month had undergone a recent surgery. Indication for antifungal prescribing was prophylaxis in 38% and treatment in 62% [empirical (57%), preemptive (13%), and targeted (30%)]. Fluconazole was the most common agent both for prophylaxis and treatment, whereas liposomal amphotericin B was the most frequent agent for targeted treatment. The majority (63%) of patients on prophylaxis were oncology or transplant patients. Common reasons for empirical and targeted treatment were persistent fever/other signs of infections in high-risk patients (61%) and Candida infections (100%), respectively. For targeted treatment, the most frequent pathogens were Candida albicans (37%) and Candida parapsilosis (32%).

Conclusions: Most antifungal prescriptions across European PICUs were for treatment. Fluconazole was the most frequently prescribed antifungal. These surveillance data can guide antifungal stewardship strategies in PICUs.

Although the current risk of avian influenza A/H5N1 Virus infection in humans is low, children represent a high-risk group for severe disease as virus evolves. A/H5N1 vaccine development, clinical trials, and implementation strategies for infants and children should be prioritized. Highly pathogenic avian influenza A/H5N1 Virus has been found in multiple US states since 2024. While human infection risk is currently low, children are a high-risk group for severe infection as the virus evolves. Preventive efforts should prioritize children in vaccine and therapeutic clinical trials and vaccine implementation strategies.

Background: To ensure the Pediatric Infectious Diseases (ID) Certifying Examination remains aligned with current clinical practice, the American Board of Pediatrics (ABP) conducted a comprehensive practice analysis to update the exam content outline.

Methods: A panel of 9 pediatric ID physicians identified 34 core tasks across 5 performance domains to guide revisions to the existing outline. The panel identified relevant, testable knowledge areas aligned with these tasks and organized them into 22 domains and 186 initial subdomains. A nationwide validation survey of board-certified pediatric ID physicians collected relevance ratings and feedback on missing or outdated topics and suggested exam weights, which were used to guide further revisions. Subsequently, the pediatric ID subboard conducted an item reclassification process, which resulted in additional refinement.

Results: The final content outline comprises 22 domains and 196 subdomains, with updated domain weights to better reflect the clinical landscape. Notably, domains such as cardiovascular, bone and joint, and urologic infections increased in weight, while antimicrobial principles decreased.

Conclusions: This rigorous, inclusive process strengthens the exam's content validity and supports the ABP's goal of certifying physicians who possess the knowledge needed to deliver safe and effective care.

Background: The Japanese Society of Chemotherapy developed practical area under the concentration-time curve (AUC)-guided therapeutic drug monitoring (PAT), a freely available web-based application widely used in Japan to support AUC-guided dosing of vancomycin. Its broad adoption has generated a substantial real-world pharmacokinetic database. Although PAT includes a preliminary pediatric model based on data from American children aged 3 months or older, that model requires further optimization. This study aimed to develop a population pharmacokinetic (popPK) model specifically for Japanese pediatric patients and to compare its performance with existing models.

Methods: We utilized a real-world database collected through PAT between December 2022 and October 2024, comprising 1673 pediatric patients aged 3 months or older. Population pharmacokinetic analysis was performed using nonlinear mixed-effects modeling, with comparisons made against 5 existing models.

Results: The developed model demonstrated strong a priori predictive performance for empirical vancomycin dosing, with a mean prediction error of 0.2 μg/mL and a mean absolute prediction error of 5.6 μg/mL. These results showed no apparent bias. Graphical diagnostics confirmed optimal a priori prediction in the developed model. A posteriori predictive performance-used for Bayesian posterior dosing-was similarly favorable across all models. Notably, 2-point sampling produced significantly different clearance estimates compared with 1-point sampling in 21 of 116 patients (18.1%).

Conclusions: For Japanese pediatric patients aged 3 months or older, the developed popPK model is suitable for both empirical and Bayesian-guided vancomycin dosing. Two-point sampling improves the accuracy of clearance estimation and is recommended when feasible.

Background: There are no established recommendations for the most suitable treatment of children with immune-tolerant chronic hepatitis B (CHB).To evaluate the clinical outcome of combination therapy among treatment-naïve children with immune-tolerant CHB, we conducted this study.

Methods: We retrospectively identified pediatric patients who were diagnosed with immune-tolerant CHB and who received combination therapy with interferon-alpha or peginterferon-alpha-2a plus entecavir at Hunan Children's Hospital between August 2014 and April 2023. A total of 106 patients were ultimately enrolled in the study. Complete clinical data were collected for all the enrolled patients. The associations between baseline characteristics and HBsAg loss were assessed using Cox proportional hazards regression. Restricted cubic spline (RCS) plots were constructed to portray the association between HBsAg loss and patient age.

Results: After a median follow-up of 87 weeks, 23.5% (25/106) of the participants achieved sustained HBsAg loss, with a cumulative incidence of 44.9%. Proportional hazard regression indicated a significant association between achieving HBsAg loss and age, HBsAg level, and HBsAb level at baseline. The RCS plots suggested that, for pediatric patients, initiating antiviral therapy for immune-tolerant CHB might be most beneficial when they are less than 5 years old. Seventy-five (70.8%) patients experienced adverse events (AEs) following interferon therapy, with no severe AEs leading to treatment discontinuation.

Conclusions: The combination therapy led to favorable clinical outcomes for children with immune-tolerant CHB. Moreover, young age and low HBsAg and high HBsAb levels at baseline are predictors of a clinical cure.

Background: Bacterial bloodstream infections (BSIs) cause morbidity and mortality in children with chemotherapy-associated neutropenia. While levofloxacin prophylaxis reduces BSI incidence, breakthrough infections occur in ~20%, often with fluoroquinolone non-susceptible (FQN-NS) gram-negative (GN) pathogens. The impact of FQN-NS on outcomes of GN BSI remains unknown. This study compares outcomes in pediatric patients with hematologic malignancies following FQN-NS vs. fluoroquinolone-susceptible (FQN-S) GN BSI.

Methods: A single-center cohort of pediatric patients with hematologic malignancies and neutropenia-associated GN BSI between 2014 and 2023 was retrospectively collected. The exposure was dichotomized as FQN-NS vs. FQN-S. Primary outcomes were intensive care unit admission and 30-day all-cause mortality, assessed from the day before to 30 days after blood culture collection. Modified Poisson regression with inverse probability of treatment weighting (IPTW) was used to balance covariates including age, calendar year of diagnosis, time from malignancy onset, cumulative neutropenia, granulocyte colony-stimulating factor use, international status, relapse/refractory disease, and type of underlying hematologic malignancy. A subgroup analysis assessed effect modification by resistance to empiric therapy. Only 5 patients contributed multiple events; clustering adjustments were not made.

Results: Among 119 GN BSI events, 82 (68.9%) were FQN-S and 37 (31.1%) FQN-NS. In IPTW-adjusted analyses, FQN-NS BSI was associated with higher 30-day all-cause mortality (aRR: 2.62, 95% CI: 0.39-17.64) and sepsis-related mortality (aRR: 2.60, 95% CI: 0.16-41.65), although confidence intervals were wide and not statistically significant. In a subgroup restricted to patients who received effective empiric therapy, estimates further reverted toward the null.

Conclusions: Fluoroquinolone non-susceptible GN BSI during neutropenia after chemotherapy was associated with increased 30-day all-cause and sepsis-related mortality in pediatric patients with hematologic malignancies, although not statistically significant. Effect modification by empiric therapy may have contributed to this association, suggesting that FQN-NS itself may not directly drive poor outcomes, but its impact appears mediated through resistance to empiric therapy, which is associated with worse outcomes.

Microbiome disruption is a proposed mechanism for the observed differences in child health outcomes by maternal HIV status, but the early neonatal microbiome of HIV-exposed (HE) newborns is not well-studied. We used 16S ribosomal ribonucleic acid sequencing to analyze the microbiome composition of nasal, skin, and rectal samples collected ≤72 h after birth from 57 hospitalized neonates in Botswana, 33% of whom were HE. Beta diversity differed by anatomic compartment (P = .001) and days since birth; however, interindividual differences were greater than those by anatomic site (P = .001). There were not significant differences by maternal HIV status. When timing of maternal HIV diagnosis was accounted for, however, we noted statistically significant differences in beta diversity for nasal and skin swabs. Microbial composition of samples from neonates with mothers diagnosed with HIV prior to pregnancy were more similar to samples from HIV-unexposed than HE neonates with mothers diagnosed with HIV during this pregnancy (P = .03 and P < .01 in skin and nasal, respectively) suggesting that microbiome variations mediated by HIV exposure might only emerge later in infancy. In the entire cohort, we examined differences in relative taxa abundance of neonatal pathogens and other species of clinical interest. We noted differences by anatomic compartment, for example, increased Klebsiella pneumoniae in rectal samples and increased Acinetobacter baumannii in nasal samples, whereas other pathogens expected to differ by body site did not, for example, Enterococcus faecium and Streptococcus agalactiae, highlighting that in the early neonatal microbiome exposures may have a significant impact on microbiome development.

In prior work, we demonstrated that clinician audit and feedback reports summarizing adherence to appropriate antibiotic choice and duration metrics in previously healthy children with nonsevere community-acquired pneumonia were associated with improved antibiotic use in this population. In this exploratory study, we evaluated the off-target impact of these reports on antibiotic choice and duration in a small cohort of medically complex children cared for concurrently by these same clinicians. The feedback report-based intervention was also associated with an increase in adherence to the appropriate antibiotic choice and duration metrics among the medically complex children, despite these children being excluded from the reports. These preliminary, hypothesis-generating findings provide proof-of-principle that the impact of clinician feedback reports is broader than the population specifically included in the report, and should inform future studies evaluating the safety and effectiveness of feedback-report-based interventions.