Journal of the Pediatric Infectious Diseases Society最新文献

{"title":"Oral Cephalexin Population Pharmacokinetics and Target Attainment Analysis in Infants 7-60 Days Old.","authors":"Andrew S Haynes, Zixuan Wei, Marc H Scheetz, Daniel Gonzalez, Kevin Messacar, Sonya Tang Girdwood, Charles A Peloquin, Douglas N Fish, Peter Anderson","doi":"10.1093/jpids/piaf088","DOIUrl":"https://doi.org/10.1093/jpids/piaf088","url":null,"abstract":"<p><strong>Background: </strong>There are limited data to guide oral antibiotic dosing in neonates and young infants, particularly for intravenous (IV) to oral transition. Cephalexin is a promising oral treatment for neonatal pathogens, including Enterobacterales and methicillin-susceptible Staphylococcus aureus (MSSA). However, maturational changes in gastrointestinal absorption and kidney function during early infancy complicate extrapolation of dosing from older populations. We evaluated cephalexin pharmacokinetics (PK) and simulated dosing strategies to achieve pharmacodynamic (PD) targets in infants ≤60 days old.</p><p><strong>Methods: </strong>This prospective, single-center study enrolled infants 0-60 days receiving cephalexin either as part of routine clinical care or as a single 25 mg/kg study dose. Plasma concentrations were analyzed using non-linear mixed-effects modeling. Simulations assessed the probability of target attainment (PTA) for free time above MIC (fT>MIC) for ≥ 50% and ≥ 70% of the dosing interval across MICs 1-16 mg/L, assuming 10% protein binding. We also simulated the cumulative fractional response (CFR) using typical MIC distributions for Enterobacterales and MSSA.</p><p><strong>Results: </strong>The analysis included 144 samples from 33 infants with median post-natal age 31 days (range 9-56) and median gestational age 37 weeks (range 29-41). A one-compartment model with first-order absorption and lag time best described the data. Weight influenced apparent volume of distribution and apparent clearance. Additionally, we identified a maturational effect on absorption rate using post-natal age and on apparent clearance using post-menstrual age. For Enterobacterales, 25 mg/kg/dose every 6 hours achieved >90% CFR for a 50% fT>MIC target. For MSSA, 25 mg/kg/dose every 8 hours was sufficient. Higher or more frequent dosing was required to meet the more stringent 70% fT>MIC target.</p><p><strong>Conclusions: </strong>Oral cephalexin can achieve necessary PD targets in infants 7-60 days old. These findings support the use of model-informed dosing strategies to guide safe and effective oral antibiotic use in early infancy, including for IV-to-oral transition.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of vancomycin population pharmacokinetic models for pediatric patients using a real-world web application database.","authors":"Kazutaka Oda, Kensuke Shoji, Kazuaki Matsumoto, Hideki Kawamura, Yoshio Takesue, Aakari Shigemi, Toshimi Kimura","doi":"10.1093/jpids/piaf087","DOIUrl":"https://doi.org/10.1093/jpids/piaf087","url":null,"abstract":"<p><strong>Background: </strong>The Japanese Society of Chemotherapy developed Practical AUC-guided Therapeutic Drug Monitoring (PAT), a freely available web-based application widely used in Japan to support area under the concentration-time curve (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 three 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.</p><p><strong>Methods: </strong>We utilized a real-world database collected through PAT between December 2022 and October 2024, comprising 1,673 pediatric patients aged three months or older. PopPK analysis was performed using nonlinear mixed-effects modeling, with comparisons made against five existing models.</p><p><strong>Results: </strong>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, two-point sampling produced significantly different clearance estimates compared to one-point sampling in 21 of 116 patients (18.1%).</p><p><strong>Conclusions: </strong>For Japanese pediatric patients aged three 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.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evidence and Interventions to Reduce the Risk of Cardiovascular-Related Morbidity and Mortality in Youth with Perinatally Acquired HIV.","authors":"Dannielle Grayer, Sahera Dirajlal-Fargo","doi":"10.1093/jpids/piaf084","DOIUrl":"https://doi.org/10.1093/jpids/piaf084","url":null,"abstract":"","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empiric Antibiotic Therapy for Mycoplasma pneumoniae Pneumonia in Children: A Pro/Con Discussion.","authors":"Elizabeth C Lloyd, Joshua Wolf","doi":"10.1093/jpids/piaf075","DOIUrl":"10.1093/jpids/piaf075","url":null,"abstract":"<p><p>Mycoplasma pneumoniae is a common respiratory pathogen of increasing clinical interest due to a recent rise in cases in the United States and worldwide following a period of reduced activity during the COVID-19 pandemic. While most cases are mild, M pneumoniae can cause severe community-acquired pneumonia (CAP), and cannot be reliably distinguished from other common causes of CAP based solely on features of clinical presentation or imaging. However, testing to confirm a diagnosis of M pneumoniae, when it is suspected, can be logistically challenging in some clinical settings. It also remains unclear which patients with M pneumoniae CAP benefit from antibiotic treatment, which raises the question of whether treatment should be offered, particularly when the diagnosis is not confirmed. This pro/con discussion explores the available data to support or refute routine testing and empiric antibiotic treatment for M pneumoniae.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Antibiotic Discontinuation in Pediatric Suspected Septic Arthritis With No Pathogen Identified: Results of a 6-Year Protocol-Based Observational Study.","authors":"Yannis Lassoued, Cindy Mallet, Philippe Bidet, Juliette Goutines, Jeanne Truong, Maud Gits, Brice Ilharreborde, Stéphane Bonacorsi, Anne-Laure Simon, Marion Caseris","doi":"10.1093/jpids/piaf080","DOIUrl":"10.1093/jpids/piaf080","url":null,"abstract":"<p><p>In a 6-year observational study of 45 children with suspected septic arthritis and no pathogen identified, early antibiotic discontinuation based on strict clinical and biological criteria was not associated with relapse during the 6-month period following hospitalization, supporting this approach may be safe and reduce unnecessary antibiotic exposure.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145000845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hospitalizations Associated With Respiratory Syncytial Virus Illness Among Children and Adolescents in Ontario, Canada.","authors":"Alexandra Goyette, Ana Gabriela Grajales, Deshayne B Fell, Sophia Rodopoulou, Ceryl Tan, Natalie Nightingale, Maria Esther Perez Trejo, Calum S Neish, Sazini Nzula","doi":"10.1093/jpids/piaf079","DOIUrl":"10.1093/jpids/piaf079","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) illness poses a significant burden in children yet is understudied in those >2 years old.</p><p><strong>Methods: </strong>We identified patients aged ≤17 years hospitalized with RSV between July 2010 and March 2023 using Ontario's administrative healthcare data. RSV-specific hospitalizations were defined by ICD-10-CA codes (B97.4, J12.1, J20.5, J21.0) and included overnight stays. Key outcomes included hospitalization frequency, intensive care unit (ICU) use, mechanical ventilation, supplemental oxygen, length of stay, mortality, and costs. Risk conditions included chronic respiratory diseases, congenital malformations, and cystic fibrosis.</p><p><strong>Results: </strong>There were 23 930 RSV hospitalizations; annual counts ranged from 1356 (2010-2011) to 4298 (2022-2023). Children <2 years accounted for 84% of hospitalizations, though risk conditions were more common in those aged 2-17 years (35% vs. 7%). In 2022-2023, hospitalizations were ~2-fold, ~3-fold, and ~5-fold higher than previous years (2010-2021) for those <12 months, 12-<24 months, and 2-17 years, respectively. Median length of stay was 69 h. Annual median cost per hospitalization was $5070 (IQR: $4486-6742). ICU admission occurred in 12% of cases, with median costs over twice that of non-ICU stays ($12 042 vs. $5070). ICU use ranged from 7% to 16% in <2 years and 10%-35% in 2-17 years. In-hospital mortality was 0.12%, higher among those with risk conditions (<2 years: 0.61%; 2-17 years: 1.02%).</p><p><strong>Conclusions: </strong>This study highlighted the burden associated with RSV hospitalizations for people aged ≤17 years and those who may be more impacted by RSV illness.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12476832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Rheumatic Fever During a Surge of Group A Streptococcus Disease in a US Children's Hospital System.","authors":"J Chase McNeil, Richard Bui, Lauren M Sommer, Meghan Walther, Tam T Doan, Marietta Deguzman, Misu Sanson, Anthony R Flores","doi":"10.1093/jpids/piaf078","DOIUrl":"10.1093/jpids/piaf078","url":null,"abstract":"","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Influence of Maternal Staphylococcus aureus Anti-Hla Neutralizing Antibody on Infant Skin and Soft Tissue Development in the First Year of Life.","authors":"Carol M Kao, Kristine M Wylie, Mary G Boyle, Alaina Schneider, Rachel Uhlir, Scott L Crick, Juliane Bubeck Wardenburg, Stephanie A Fritz","doi":"10.1093/jpids/piaf077","DOIUrl":"10.1093/jpids/piaf077","url":null,"abstract":"<p><strong>Background: </strong>Staphylococcus aureus is the leading cause of infectious-related deaths. Vaccine development has been hampered by the recall of nonprotective immune responses from prior exposure, suggesting an effective vaccine may need to be given early in life. The goal of this pilot study was to correlate the maternal serologic response against S. aureus to an infant's risk for skin and soft tissue infection (SSTI) and colonization in the first year of life.</p><p><strong>Methods: </strong>Pregnant women were enrolled and maternal-infant dyads followed for 12 months. Maternal third trimester and cord blood were obtained to determine the anti-S. aureus IgG and anti-α-toxin (Hla) neutralizing antibody (NAb) titers. Serial surveys and skin swabs were obtained from mothers at enrollment and from infants longitudinally to ascertain S. aureus colonization status and the incidence of SSTI.</p><p><strong>Results: </strong>Sixty-three pregnant women were enrolled, 54% with history of SSTI or asymptomatic S. aureus colonization at enrollment. Within 48-h of delivery, 23% of infants had S. aureus colonization and 43% at 1-month. Maternal S. aureus colonization resulted in 7.4 increased odds of infant colonization at delivery. Higher cord blood anti-Hla Nab titer was associated with significantly lower risk for infant SSTI in the first year of life.</p><p><strong>Conclusions: </strong>S. aureus colonization occurs early in life, with over 40% of infants colonized by 1-month. These results are the first to demonstrate an association between higher transplacental anti-Hla NAb and protection against infant SSTI in the first year of life. Overall, these findings support Hla as a promising vaccine target.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144958741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of maternal HIV status on the early neonatal microbiome.","authors":"M Carolyn, Jonathan Strysko, One Bayani, Banno Moorad, Nametso Ntlhako, Ngwao Nwako, Weiming Hu, Ceylan Tanes, Ahmed M Moustafa, Steven M Jones, Britt Nakstad, Alemayehu M Gezmu, Tonya Arscott-Mills, David M Goldfarb, Andrew P Steenhoff, Melissa Richard-Greenblatt, Tichaona Machiya, Tefelo Thela, Margaret Mokomane, Giacomo M Paganotti, Moses Vurayai, Morgan Zalot, Mickael Boustany, Paul J Planet, Susan Coffin, Kyle Bittinger","doi":"10.1093/jpids/piaf076","DOIUrl":"https://doi.org/10.1093/jpids/piaf076","url":null,"abstract":"<p><p>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 hours 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.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144992787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monomicrobial Rothia spp. Bloodstream Infections in Pediatric Patients and Literature Review.","authors":"Joshua D Green, Preeti Jaggi, Mark D Gonzalez, Pratik A Patel","doi":"10.1093/jpids/piaf074","DOIUrl":"10.1093/jpids/piaf074","url":null,"abstract":"<p><p>We examined 51 monomicrobial Rothia spp. blood cultures from 2015 to 2024. Seventy-one percent occurred in cancer/hematopoietic cell transplantation patients, of which 97% were treated as true bloodstream infections and 78% followed recent broad-spectrum antibiotics. Prolonged (>4 day) fever was common. Routine Rothia spp. susceptibility testing is warranted to gauge antibiotic-driven breakthrough infection.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144835495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}