Ville Lindholm, Suvi Mattila, Kimmo Halt, Niko Paalanne, Tytti Pokka, Vesa Mäki-Koivisto, Laura E Savolainen, Minna Honkila, Terhi Ruuska-Loewald
Background: Less invasive alternatives for nasopharyngeal swab samples are needed for the detection of respiratory pathogens in children.
Methods: Prospective diagnostic study comparing the accuracy and convenience of saliva and mouthwash samples with nasopharyngeal swab samples in detecting respiratory pathogens using a multiplex polymerase chain reaction panel for 19 respiratory viruses or viral subtypes and 4 respiratory bacteria. Acutely ill children aged 2-16 years with a suspected respiratory tract infection provided saliva and mouthwash samples in addition to a nasopharyngeal swab sample.
Results: Altogether, 850 samples were obtained from 302 children, including 300 nasopharyngeal swab, 277 saliva, and 273 mouthwash samples. Among 302 participants (mean age, 9.7 years [SD, 3.0], 151 males [50%]), at least 1 respiratory pathogen was detected in 219 (73%). The most common pathogens in nasopharyngeal swab samples were rhinovirus or enterovirus (86 [29%]), Mycoplasma pneumoniae (46 [15%]), influenza viruses A and B (32 [11%]), adenovirus (15 [5.0%]), and respiratory syncytial virus (14 [4.7%]). The sensitivity of saliva samples was 71% (95% CI, 60%-81%) for rhinovirus or enterovirus, 93% (95% CI, 82%-99%) for M. pneumoniae, 86% (95% CI, 64%-97%) for influenza A virus, and 88% (95% CI, 47%-100%) for influenza B virus. The sensitivity of mouthwash samples was 48% (95% CI, 36-60%) for rhinovirus or enterovirus, 90% (95% CI, 77%-97%) for M. pneumoniae, 73% (95% CI, 50%-89%) for influenza A virus, and 67% (95% CI, 30%-93%) for influenza B virus. In total, 99% (257/260) of the children preferred either saliva or mouthwash samples to nasopharyngeal swab samples.
Conclusions: The sensitivity of saliva and mouthwash samples varied across respiratory pathogens in children. Less invasive saliva samples may serve as an alternative to nasopharyngeal swab samples for detecting certain respiratory pathogens in children.
{"title":"Detection of Respiratory Pathogens in Saliva and Mouthwash Samples in Children.","authors":"Ville Lindholm, Suvi Mattila, Kimmo Halt, Niko Paalanne, Tytti Pokka, Vesa Mäki-Koivisto, Laura E Savolainen, Minna Honkila, Terhi Ruuska-Loewald","doi":"10.1093/jpids/piaf105","DOIUrl":"10.1093/jpids/piaf105","url":null,"abstract":"<p><strong>Background: </strong>Less invasive alternatives for nasopharyngeal swab samples are needed for the detection of respiratory pathogens in children.</p><p><strong>Methods: </strong>Prospective diagnostic study comparing the accuracy and convenience of saliva and mouthwash samples with nasopharyngeal swab samples in detecting respiratory pathogens using a multiplex polymerase chain reaction panel for 19 respiratory viruses or viral subtypes and 4 respiratory bacteria. Acutely ill children aged 2-16 years with a suspected respiratory tract infection provided saliva and mouthwash samples in addition to a nasopharyngeal swab sample.</p><p><strong>Results: </strong>Altogether, 850 samples were obtained from 302 children, including 300 nasopharyngeal swab, 277 saliva, and 273 mouthwash samples. Among 302 participants (mean age, 9.7 years [SD, 3.0], 151 males [50%]), at least 1 respiratory pathogen was detected in 219 (73%). The most common pathogens in nasopharyngeal swab samples were rhinovirus or enterovirus (86 [29%]), Mycoplasma pneumoniae (46 [15%]), influenza viruses A and B (32 [11%]), adenovirus (15 [5.0%]), and respiratory syncytial virus (14 [4.7%]). The sensitivity of saliva samples was 71% (95% CI, 60%-81%) for rhinovirus or enterovirus, 93% (95% CI, 82%-99%) for M. pneumoniae, 86% (95% CI, 64%-97%) for influenza A virus, and 88% (95% CI, 47%-100%) for influenza B virus. The sensitivity of mouthwash samples was 48% (95% CI, 36-60%) for rhinovirus or enterovirus, 90% (95% CI, 77%-97%) for M. pneumoniae, 73% (95% CI, 50%-89%) for influenza A virus, and 67% (95% CI, 30%-93%) for influenza B virus. In total, 99% (257/260) of the children preferred either saliva or mouthwash samples to nasopharyngeal swab samples.</p><p><strong>Conclusions: </strong>The sensitivity of saliva and mouthwash samples varied across respiratory pathogens in children. Less invasive saliva samples may serve as an alternative to nasopharyngeal swab samples for detecting certain respiratory pathogens in children.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12771362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573607","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}
Despite widespread vaccination, the United States has seen a stark increase in pertussis cases over the past year. Disease profiles vary across age groups, with infants at the greatest risk. The development of next generation pertussis vaccines will involve updated antigenic content, novel adjuvants, and live-attenuated constructs, potentially leveraging controlled human infection models of pertussis.
{"title":"Pertussis: Modern Approaches to an Ancient Adversary.","authors":"C Buddy Creech, Dakota Musgrave","doi":"10.1093/jpids/piaf098","DOIUrl":"10.1093/jpids/piaf098","url":null,"abstract":"<p><p>Despite widespread vaccination, the United States has seen a stark increase in pertussis cases over the past year. Disease profiles vary across age groups, with infants at the greatest risk. The development of next generation pertussis vaccines will involve updated antigenic content, novel adjuvants, and live-attenuated constructs, potentially leveraging controlled human infection models of pertussis.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409566","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}
Zheyi Teoh, Ariana P Toepfer, Chelsea Rohlfs, Christopher J Harrison, Eileen J Klein, Elizabeth P Schlaudecker, Geoffrey A Weinberg, Janet A Englund, John V Williams, Julie A Boom, Leila C Sahni, Marian G Michaels, Natasha Halasa, Laura S Stewart, Peter G Szilagyi, Rangaraj Selvarangan, Meredith L McMorrow, Heidi Moline, Mary Allen Staat
Introduction: Bronchiolitis, pneumonia, and croup account for a substantial burden of pediatric hospitalizations. We aim to provide an updated, multi-center, multi-pathogen evaluation of viral detections seen with these acute respiratory illness (ARI) syndromes before and after the COVID-19 pandemic.
Methods: We included children <5 years with a diagnosis of bronchiolitis, pneumonia, or croup during 2017-2023 from the New Vaccine Surveillance Network. Respiratory viruses were detected with a research ± clinical respiratory swabs; demographic and clinical data were obtained from caregiver interview and chart review. Virus-specific proportions across all three ARI syndromes were described, including comparisons stratified by age, surveillance year including pre- (2017-2019) and post (2021-2023) COVID-19 onset periods, and underlying medical condition.
Results: Among 14 340 cases of bronchiolitis, 4423 cases of pneumonia, and 2367 cases of croup, >80% had one or more respiratory virus detected. Respiratory syncytial virus (RSV) was the most frequent virus detected in bronchiolitis (41%) and pneumonia (26%), with a similar distribution across the COVID-19 onset periods. Parainfluenza virus (PIV) was the most frequent virus detected in croup (28%), but detections fell in the post-COVID-19 onset period by 8.4%; there was a comparable proportion of SARS-CoV-2 detections (7.6%) that emerged among croup cases. Rhinoviruses/enteroviruses (RV/EV) were the second most frequently detected virus across all three ARI syndromes and were the predominant virus in children <6 months and children with an underlying medical condition diagnosed with croup. Codetections were present in 17%-19% of bronchiolitis, pneumonia, and croup cases.
Discussion: We found a high proportion of respiratory viral detections in children <5 years with bronchiolitis, pneumonia, or croup, particularly with RSV, RV/EV, and PIV. Most viruses were identified in similar proportions before and after the emergence of SARS-CoV-2, except for PIV and influenza virus. In our cohort, there was a high proportion of viral detection across all three ARI syndromes, with RV/EV frequently detected in certain age groups and among children with underlying conditions.
{"title":"Viral Detection in Children <5 Years with Bronchiolitis, Pneumonia, and Croup, New Vaccine Surveillance Network, 2017-2023.","authors":"Zheyi Teoh, Ariana P Toepfer, Chelsea Rohlfs, Christopher J Harrison, Eileen J Klein, Elizabeth P Schlaudecker, Geoffrey A Weinberg, Janet A Englund, John V Williams, Julie A Boom, Leila C Sahni, Marian G Michaels, Natasha Halasa, Laura S Stewart, Peter G Szilagyi, Rangaraj Selvarangan, Meredith L McMorrow, Heidi Moline, Mary Allen Staat","doi":"10.1093/jpids/piaf096","DOIUrl":"10.1093/jpids/piaf096","url":null,"abstract":"<p><strong>Introduction: </strong>Bronchiolitis, pneumonia, and croup account for a substantial burden of pediatric hospitalizations. We aim to provide an updated, multi-center, multi-pathogen evaluation of viral detections seen with these acute respiratory illness (ARI) syndromes before and after the COVID-19 pandemic.</p><p><strong>Methods: </strong>We included children <5 years with a diagnosis of bronchiolitis, pneumonia, or croup during 2017-2023 from the New Vaccine Surveillance Network. Respiratory viruses were detected with a research ± clinical respiratory swabs; demographic and clinical data were obtained from caregiver interview and chart review. Virus-specific proportions across all three ARI syndromes were described, including comparisons stratified by age, surveillance year including pre- (2017-2019) and post (2021-2023) COVID-19 onset periods, and underlying medical condition.</p><p><strong>Results: </strong>Among 14 340 cases of bronchiolitis, 4423 cases of pneumonia, and 2367 cases of croup, >80% had one or more respiratory virus detected. Respiratory syncytial virus (RSV) was the most frequent virus detected in bronchiolitis (41%) and pneumonia (26%), with a similar distribution across the COVID-19 onset periods. Parainfluenza virus (PIV) was the most frequent virus detected in croup (28%), but detections fell in the post-COVID-19 onset period by 8.4%; there was a comparable proportion of SARS-CoV-2 detections (7.6%) that emerged among croup cases. Rhinoviruses/enteroviruses (RV/EV) were the second most frequently detected virus across all three ARI syndromes and were the predominant virus in children <6 months and children with an underlying medical condition diagnosed with croup. Codetections were present in 17%-19% of bronchiolitis, pneumonia, and croup cases.</p><p><strong>Discussion: </strong>We found a high proportion of respiratory viral detections in children <5 years with bronchiolitis, pneumonia, or croup, particularly with RSV, RV/EV, and PIV. Most viruses were identified in similar proportions before and after the emergence of SARS-CoV-2, except for PIV and influenza virus. In our cohort, there was a high proportion of viral detection across all three ARI syndromes, with RV/EV frequently detected in certain age groups and among children with underlying conditions.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308615","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":"Impact of SARS-CoV-2 pandemic on Pediatric inpatients with invasive group a streptococcal infections (iGAS): results of a National Survey.","authors":"Zweifel Nils, Güsewell Sabine, Jaboyedoff Manon, Albrich Werner, Aebi Christoph, Niederer-Lohner Anita, Kahlert Christian","doi":"10.1093/jpids/piaf097","DOIUrl":"10.1093/jpids/piaf097","url":null,"abstract":"","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409546","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}
Diego R Hijano, Walter A Orenstein, Carlos R Oliveira
Reduced vaccine coverage has led to a resurgence of vaccine-preventable diseases, threatening decades of public health progress. This perspective explores the rise in measles cases and outlines how the pediatric infectious disease community can rebuild vaccine confidence to reverse this trend.
{"title":"Measles Resurgence and the Fragility of Herd Immunity: Implications for Pediatric Infectious Disease Practice.","authors":"Diego R Hijano, Walter A Orenstein, Carlos R Oliveira","doi":"10.1093/jpids/piaf094","DOIUrl":"10.1093/jpids/piaf094","url":null,"abstract":"<p><p>Reduced vaccine coverage has led to a resurgence of vaccine-preventable diseases, threatening decades of public health progress. This perspective explores the rise in measles cases and outlines how the pediatric infectious disease community can rebuild vaccine confidence to reverse this trend.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12581858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145308589","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}
Huan Vinh Dong, Neema Pithia, Choiyuk Chiang, Megan Halbrook, Melanie Barr, Sherry Yin, Adriana Diaz, James Beekley, Nava Yeganeh
Nirsevimab reduces respiratory syncytial virus-related hospitalizations and is recommended for infants shortly after birth during RSV season. We compared characteristics of newborns who received nirsevimab to those who received hepatitis B vaccine within one week of life to better identify gaps in coverage and target public health outreach. One year after the introduction of nirsevimab, fewer infants received the recommended birth dose of nirsevimab as compared to hepatitis B vaccine.
{"title":"Factors Associated With Newborn Nirsevimab Administration in Los Angeles County During the 2024 Respiratory Syncytial Virus Season.","authors":"Huan Vinh Dong, Neema Pithia, Choiyuk Chiang, Megan Halbrook, Melanie Barr, Sherry Yin, Adriana Diaz, James Beekley, Nava Yeganeh","doi":"10.1093/jpids/piaf095","DOIUrl":"10.1093/jpids/piaf095","url":null,"abstract":"<p><p>Nirsevimab reduces respiratory syncytial virus-related hospitalizations and is recommended for infants shortly after birth during RSV season. We compared characteristics of newborns who received nirsevimab to those who received hepatitis B vaccine within one week of life to better identify gaps in coverage and target public health outreach. One year after the introduction of nirsevimab, fewer infants received the recommended birth dose of nirsevimab as compared to hepatitis B vaccine.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12596719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145345967","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}
Background: The COVID-19 pandemic magnified longstanding racial and ethnic disparities in pediatric health, but it is unclear which populations experienced the largest disparities. Our objective was to determine whether disparities in COVID-19 severity differed with respect to patient factors analyzed as effect modifiers.
Methods: Using data from the Premier Healthcare Database, this retrospective cohort study included encounters among inpatients < 19 years old from April 2020 through September 2022 in the USA with a COVID-19 diagnosis. Outcomes of COVID-19 severity were intensive care unit (ICU) admission and ventilator use. Comparisons between Black and White patients and Hispanic and White patients were adjusted for confounders using propensity score weights, reported as risk differences (RDs) in percentage points, and tested for heterogeneity (interaction P) across subgroups of effect modifiers such as complex chronic conditions (CCCs) and insurance status.
Results: Of 8947 pediatric inpatients with primary COVID-19 diagnosis, 3858 were White, 2153 were Black, and 2936 were Hispanic. Among children with a CCC, 14.3% of Black inpatients required a ventilator compared to 9.8% of White inpatients; among children without a CCC, 3.2% of both Black and White inpatients required a ventilator (RDs 4.5 vs 0.0; interaction P = .013). Comparisons of Hispanic and White inpatients showed a similar trend in ventilator use, with larger disparities among inpatients with CCCs and no difference among those without CCCs (RDs 2.7 vs -0.7; interaction P=.031). Among children with government insurance, 25.9% of Black inpatients were admitted to the ICU compared to 20.8% of White inpatients; among children with private insurance, Black and White inpatients had comparable ICU admission rates of 20.0% and 21.4%, respectively (RDs 5.1 vs -1.4; interaction P = .025).
Conclusions: Among hospitalized children, racial and ethnic disparities in COVID-19 severity were largest for those with CCCs or government insurance. These results can help identify target populations for interventions to reduce inequity.
背景:2019冠状病毒病大流行放大了儿科健康方面长期存在的种族和民族差异,但尚不清楚哪些人群的差异最大。我们的目的是确定COVID-19严重程度的差异是否与作为效果调节剂分析的患者因素有关。方法:采用来自Premier Healthcare数据库的数据,对住院患者进行回顾性队列研究。结果:8947例初诊COVID-19的儿科住院患者中,3858例为白人,2153例为黑人,2936例为西班牙裔。在患有CCC的儿童中,14.3%的黑人住院患者需要呼吸机,而白人住院患者的这一比例为9.8%;在没有CCC的儿童中,3.2%的黑人和白人住院患者需要呼吸机(RDs为4.5 vs. 0.0;交互作用p= 0.013)。西班牙裔和白人住院患者在呼吸机使用方面的比较显示出类似的趋势,有CCCs的住院患者差异较大,无CCCs的住院患者无差异(RDs为2.7 vs. -0.7;相互作用p= 0.031)。在有政府保险的儿童中,25.9%的黑人住院患者进入ICU,而白人住院患者的这一比例为20.8%;在拥有私人保险的儿童中,黑人和白人住院患者的ICU住院率分别为20.0%和21.4% (RDs为5.1 vs. -1.4;相互作用p= 0.025)。结论:在住院儿童中,患有CCCs或政府保险的儿童在COVID-19严重程度上的种族和民族差异最大。这些结果有助于确定干预措施的目标人群,以减少不平等现象。
{"title":"Heterogeneity in Racial and Ethnic Disparities in COVID-19 Severity Among Pediatric Inpatients in a National Healthcare Database.","authors":"David Watson, Alicen B Spaulding, Laura Norton","doi":"10.1093/jpids/piaf092","DOIUrl":"10.1093/jpids/piaf092","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 pandemic magnified longstanding racial and ethnic disparities in pediatric health, but it is unclear which populations experienced the largest disparities. Our objective was to determine whether disparities in COVID-19 severity differed with respect to patient factors analyzed as effect modifiers.</p><p><strong>Methods: </strong>Using data from the Premier Healthcare Database, this retrospective cohort study included encounters among inpatients < 19 years old from April 2020 through September 2022 in the USA with a COVID-19 diagnosis. Outcomes of COVID-19 severity were intensive care unit (ICU) admission and ventilator use. Comparisons between Black and White patients and Hispanic and White patients were adjusted for confounders using propensity score weights, reported as risk differences (RDs) in percentage points, and tested for heterogeneity (interaction P) across subgroups of effect modifiers such as complex chronic conditions (CCCs) and insurance status.</p><p><strong>Results: </strong>Of 8947 pediatric inpatients with primary COVID-19 diagnosis, 3858 were White, 2153 were Black, and 2936 were Hispanic. Among children with a CCC, 14.3% of Black inpatients required a ventilator compared to 9.8% of White inpatients; among children without a CCC, 3.2% of both Black and White inpatients required a ventilator (RDs 4.5 vs 0.0; interaction P = .013). Comparisons of Hispanic and White inpatients showed a similar trend in ventilator use, with larger disparities among inpatients with CCCs and no difference among those without CCCs (RDs 2.7 vs -0.7; interaction P=.031). Among children with government insurance, 25.9% of Black inpatients were admitted to the ICU compared to 20.8% of White inpatients; among children with private insurance, Black and White inpatients had comparable ICU admission rates of 20.0% and 21.4%, respectively (RDs 5.1 vs -1.4; interaction P = .025).</p><p><strong>Conclusions: </strong>Among hospitalized children, racial and ethnic disparities in COVID-19 severity were largest for those with CCCs or government insurance. These results can help identify target populations for interventions to reduce inequity.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12570028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251742","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":"Childhood Pneumonia-Related Mortality Trends in the United States, 1999-2023.","authors":"Mark I Neuman, Chris A Rees","doi":"10.1093/jpids/piaf085","DOIUrl":"10.1093/jpids/piaf085","url":null,"abstract":"","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091942","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}
Andrew S Haynes, Zixuan Wei, Marc H Scheetz, Daniel Gonzalez, Kevin Messacar, Sonya Tang Girdwood, Charles A Peloquin, Douglas N Fish, Peter Anderson
Background: 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 and simulated dosing strategies to achieve pharmacodynamic targets in infants ≤60 days old.
Methods: 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 for free time above minimum inhibitory concentration (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 using typical MIC distributions for Enterobacterales and MSSA.
Results: 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 h achieved >90% cumulative fractional response for a 50% fT > MIC target. For MSSA, 25 mg/kg/dose every 8 h was sufficient. Higher or more frequent dosing was required to meet the more stringent 70% fT > MIC target.
Conclusions: Oral cephalexin can achieve necessary pharmacodynamic 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.
{"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":"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 and simulated dosing strategies to achieve pharmacodynamic 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 for free time above minimum inhibitory concentration (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 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 h achieved >90% cumulative fractional response for a 50% fT > MIC target. For MSSA, 25 mg/kg/dose every 8 h 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 pharmacodynamic 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":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12551457/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elisavet Chorafa, Elias Iosifidis, Aisha Abdalla Alkhaaldi, Ana Arias, Benhur Sirvan Cetin, Maia De Luca, Marieke Emonts, Laura Ferreras-Antolin, Elisabetta Ghimenton-Walters, Carlos D Grasa, Andreas H Groll, Laura Herrera-Castillo, Thomas Lehrnbecher, Angela Manzanares, Katja Masjosthusmann, Susana Melendo, Natalia Mendoza-Palomar, Stéphane Paulus, Elena Rincón-López, Lorenza Romani, Maria Sdougka, Galina Solopova, Volker Strenger, Kara Tedford, Christina Tzika, Adilia Warris, Borbala Zsigmond, Emmanuel Roilides
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.
背景:入住PICU的危重儿科患者极易受到感染,包括侵袭性真菌疾病和经常使用抗真菌药物。欧洲picu的抗真菌药物使用情况尚不清楚。方法:组织了一项为期3个月、每周一次的多国点流行调查,以了解抗真菌药物的使用情况。欧洲区域10个国家的18个picu(16家医院)参与了该项目。所有在picu住院并接受全身抗真菌治疗的患者均被纳入。收集一次病区人口统计信息;在为期12周的研究期间,前瞻性地收集每周的病房和患者数据,并输入REDCap数据库。结果:在18个picu中,8个(44%)对目标组患者采取了预防措施,7/18(39%)有抗真菌管理计划,大多数(16/ 18,89%)具有生物标志物利用能力(16/16半乳甘露聚糖,13/16 β - d -葡聚糖,9/16泛真菌PCR)。记录等量患者的101个疗程;结论:欧洲picu的抗真菌处方主要用于治疗。氟康唑是最常用的抗真菌药物。这些监测数据可以指导picu的抗真菌管理策略。
{"title":"Antifungal Prescribing in European Pediatric Intensive Care Units: Results of a Multinational 3-Month Weekly Point-Prevalence Survey†.","authors":"Elisavet Chorafa, Elias Iosifidis, Aisha Abdalla Alkhaaldi, Ana Arias, Benhur Sirvan Cetin, Maia De Luca, Marieke Emonts, Laura Ferreras-Antolin, Elisabetta Ghimenton-Walters, Carlos D Grasa, Andreas H Groll, Laura Herrera-Castillo, Thomas Lehrnbecher, Angela Manzanares, Katja Masjosthusmann, Susana Melendo, Natalia Mendoza-Palomar, Stéphane Paulus, Elena Rincón-López, Lorenza Romani, Maria Sdougka, Galina Solopova, Volker Strenger, Kara Tedford, Christina Tzika, Adilia Warris, Borbala Zsigmond, Emmanuel Roilides","doi":"10.1093/jpids/piaf081","DOIUrl":"10.1093/jpids/piaf081","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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%).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":17374,"journal":{"name":"Journal of the Pediatric Infectious Diseases Society","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030098","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}