Pediatric Infections Research Articles

Practice guideline of influenza vaccination and antiviral drugs use in children(2024 editon)

Influenza is the most common acute respiratory infectious diseases among children in China. The annual seasonal influenza outbreak has a significant impact on children's health, poses a significant disease and socioeconomic burden, and arouses a wide public concern. In recent years, a number of new influenza vaccines and influenza antivirals have been approved for use in children, expanding the choices for prevention and treatment of influenza. Pediatric Infection Group, Chinese Society of Infectious Diseases of Chinese Medical Association and Infection Group, Pediatric Expert Committee of National Health Commission Capacity Building and Continuing Education, and China Clinical Practice Guidelines Alliance Methodology Committee organized a multidisciplinary guideline development group (GDG) consisting of experts in pediatrics, infectious diseases,epidemiologists,health policy,and guideline methodology proposed eight key issues concerning influenza vaccination and antiviral use from a practice perspective. Through research question construction, evidence retrieval and synthesis, evidence appraisal and evidence-to-decision discussion, recommendations and implementation suggestions were formulated. This guideline is intended to provide guidance for pediatricians at different facility levels and healthcare providers engaged in vaccination services,and institutional professionals dealing with prevention and control of infectious diseases.

Paediatric iGAS Morbidity and Mortality in Ireland 2022-2023 episodic upsurge

Abstract There was an unseasonal upsurge in invasive Group A Streptococcal (iGAS) activity in Ireland during the 2022/2023 winter period. In particular, there was an increase in the proportion of paediatric infections and a rise in the age specific death rate for those under the age of 18, from 0.10 to 1.43 per 100,000. This review aimed to describe the demographic and clinical factors associated with paediatric iGAS infection during this upsurge. All iGAS cases under the age of 16 years, notified to Public Health between 1st October and 30th June 2023, were included. A review of hospital records for each case was conducted using a standardised electronic data collection proforma. Descriptive, univariate and multivariate analysis was conducted using SPSS statistical package. There was a total of 183 cases of iGAS notified during this upsurge in Ireland. A hospital chart review was conducted for 169 of these cases, giving a response rate of 92.3%. The median age was 4 years (range 0-15,) with 44.4% (75) having a previous healthcare attendance during their illness. Varicella coinfection occurred in 27.8% (47) of cases. There was respiratory viral coinfection in 40.8% (69) of cases, and this was significantly associated with an increased risk of death RR 6.49 (95% CI 4.45 - 29.08) p < 0.05. A respiratory site of infection was also significantly associated with an increased risk of death RR 10.13 (95% CI 2.23 - 45.95) p < 0.001. However, both factors did not remain significant once adjusted for age, sex, ethnicity and deprivation index. This national review demonstrated the significant burden of paediatric iGAS morbidity and mortality during this upsurge. A significant proportion of cases, 37.9% (64) were associated with vaccine preventable illness, with respiratory viral infections and a respiratory site of infection both being significantly associated with an increased risk of death. Key messages • A significant proportion of iGAS cases were associated with a vaccine preventable illness. • A respiratory site of iGAS infection was significantly associated with an increased risk of death in paediatric cases.

Hospitalisation cost for paediatric osteomyelitis and septic arthritis in New Zealand.

Hospitalisation rates for paediatric bone and joint infection (BJI) in New Zealand (NZ) are among the highest globally. This study aims to quantify hospitalisation costs of BJI in 2018-2019. National hospitalisation data from the NZ Ministry of Health was used to describe costs associated with all paediatric hospitalisations coded for osteomyelitis or septic arthritis in those aged <16 years. Data included age, ethnic group, area level deprivation, diagnosis-related-group coding, admission length and cost-weight. Readmissions up to 24 months following the initial encounter were analysed for associated costs. More than ten million dollars was spent on hospitalisation for paediatric BJI over the study period (NZ$10 819 474). There were 869 primary hospitalisations and 229 related readmissions. Median length of stay was 7.4 days (95% confidence interval 6.8-7.9). Re-admission costs were NZ$1 196 640 within 24 months following diagnosis. Higher median hospitalisation costs occurred for children residing in the most deprived versus least deprived neighbourhoods (NZ$12 126 vs. NZ$9010, P < 0.01). NZ Māori compared with non-Māori children had longer length of stay (8.4 vs. 6.3 days, P = 0.04), more complex and severe illnesses (53% vs. 17%, P < 0.01), and higher median hospitalisation costs (NZ$11 796 vs. NZ$9581, P = 0.03). Direct BJI hospitalisation costs in 2018-2019 were NZ$10 819 474 with 11% of costs due to re-admission. Direct hospitalisation costs for paediatric BJI in NZ vary by deprivation and ethnic group. Illness complexity of paediatric BJI varies by ethnic group. Interventions are needed to reduce incidence and severity of these debilitating infections.

High SARS-CoV-2 secondary infection rates in households with children in Georgia, United States, Fall 2020—Winter 2021

BackgroundA wide range of household secondary infection rates has been reported, and the role of children in population transmission dynamics for SARS-CoV-2 remains ill-defined. We sought to better understand household infection early in the pandemic.MethodologyA cross-sectional study of 17 households in the Atlanta metropolitan area with at least one child and one case of COVID-19 in the prior 1–4 months were recruited between December 2020 and April 2021. Self-collected saliva samples were tested on a multiplexed platform to detect IgG antibodies that bind to SARS-CoV-2 antigens. Secondary infection rates (SIR) were calculated and compared.ResultsWe report results on 17 families, including 66 individuals. We found an average SIR of 0.58; children and adults were similarly infected (62% children vs. 75% adults) (p = 0.2). Two out of 17 households had a pediatric index per our definition. Number of pediatric infections per household (p = 0.18), isolation (p = 0.34), and mask wearing (p = 0.80) did not differ significantly among households with an SIR above the mean vs. those with SIR below the mean. Households with higher SIR also had a higher number of symptomatic cases (p &amp;lt; 0.001).DiscussionWe demonstrated high household SIRs at the early stages of the pandemic in late 2020 to early 2021 with similar impact on children and adults. The ease of collecting saliva and the detection of asymptomatic infections highlight the advantages of this strategy and potential for scale-up.

Antibiotic use in pediatric dental infections: knowledge and awareness levels of dentists

Antibiotics are crucial in treating infections; however, their unnecessary and incorrect use can lead to numerous health issues, notably antibiotic resistance. Evaluating the accuracy and awareness of antibiotic prescription practices among dentists, who play a significant role in antibiotic use, is critical in developing effective health policies and professional training programs. This study assesses dentists’ knowledge levels and practice habits regarding antibiotic use. Using a structured questionnaire, the research employed a cross-sectional design and was conducted with 202 general dentists, 98 pediatric dentists, and 43 oral and maxillofacial surgeons. Data were analyzed using demographic characteristics, antibiotic prescription practices, and scenario-based questions measuring knowledge levels. The results revealed that while most participants were generally knowledgeable about antibiotic use, inconsistencies in prescription practices were evident. Notably, unnecessary antibiotic prescriptions were identified in some cases, contributing to significant health issues such as antibiotic resistance. This study emphasizes the necessity of promoting conscious antibiotic use by evaluating dentists’ practices. Therefore, the urgent need for developing professional training programs and strengthening strategies to combat antibiotic resistance is paramount.

Molecular characterization of human adenovirus associated with pediatric severe acute respiratory infections in a tertiary care hospital in North East India

PurposeThe present study explored the molecular characterization of human Adenovirus (HAdV) and its strains among hospitalized SARI cases in the pediatric unit of a tertiary care hospital in North-East India.MethodsNasal and throat swabs were collected from 70 patients of Pediatric Unit, of a tertiary hospital in NE India from April 2023-October 2023. The samples were screened for the presence of HAdV using an adenovirus-specific Real-Time PCR Kit. For molecular characterization, Next Generation Sequencing (NGS) was performed by targeting the hexon gene of HAdV followed by post-sequencing analysis.ResultsOverall, 18.57% (13/70) of samples were positive for HAdV. In context of the severity of illness, 3/13 adenovirus-positive patients (23.07%) died after hospitalization, had severe pneumonia among which two were of less than one year of age. Molecular characterization using NGS indicated that 4/13 individuals were infected with HAdV-B type 3 and 5/13 patients were infected with HAdV type 7. Notably, 4/7 cases of severe pneumonia were under five years of age and associated with HAdV type 7 infection. The ratio of non-synonymous to synonymous mutation (dN/dS) was comparatively low in HAdV type 7 positive samples (dN/dS=0.31). No non-synonymous mutation was observed in HAdV-B type 3 positive samples. The higher neutrophil percentage among the death cases suggested an acute immune response.ConclusionThe study demonstrated HAdV type 7 and HAdV-B type 3 as strains associated with pediatric SARI cases from April 2023-October 2023. Further, HAdV type 7 infection was primarily linked with lower respiratory tract infections mainly severe pneumonia.

The impact of the COVID-19 pandemic on pediatric bloodstream infections and alteration in antimicrobial resistance phenotypes in Gram-positive bacteria, 2020–2022

BackgroundAlteration in the etiology of pediatric bloodstream infections (BSIs) and antimicrobial resistance (AMR) is not well known during the Coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the impact of the COVID-19 pandemic on pediatric BSIs and alteration in antimicrobial resistance phenotypes in Gram-positive bacteria.MethodsThe frequency of BSIs among children under 18 years old was retrospectively recorded in a tertiary children’s hospital in Tehran, Iran from February 2020 to December 2022. The status of COVID-19 infection using reverse transcription polymerase chain reaction, bacteremia/fungemia according to BACTEC 9120 Culture System results, characterization of bacteria using biochemical tests, and antimicrobial susceptibility patterns for Gram-positive bacterial isolates using disk diffusion method were determined. Statistical analysis was done to measure the correlation of COVID-19 infection with BSIs and AMR.ResultsOut of 13,345 COVID-19 tests and 4,194 BACTEC blood culture requests, bacteremia/fungemia were confirmed in 10.37% (435/4,194) of the patients who requested both tests simultaneously. The COVID-19 infection was confirmed in 25.3% (110/435) of the patients with bacteremia/fungemia. The infection with characterized Gram-positive bacteria (GPB) and fungi was detected in 32.3% (140/433) and 8.31% (36/433) of the cases, respectively. Coagulase-negative Staphylococcus (CNS, 72, 16.62%), S. aureus (36, 8.3%), and Enterococcus spp. (22, 5%) were among the common isolates. Candida spp. and non-Candida yeasts were detected in 6.7% and 13.4% of the cases, respectively. A positive correlation was shown between the CNS bacteremia and COVID-19 infection (p-value = 0.019). Antibiotic susceptibility testing results showed the highest frequency of resistance to azithromycin among CNS, azithromycin and tetracycline among S. aureus and tetracycline among Enterococcus spp. Methicillin-resistance phenotype in the S. aureus (MRSA) and coagulase-negative Staphylococcus spp. (MR-CNS) was detected in 40% and 61.5% of the strains, respectively and the Enterococci were resistant to vancomycin in 33.3% of the isolates.ConclusionA decline in the trend of BSIs by GPB and an increase in AMR was shown in children during the COVID-19 pandemic. Increasing antibiotic resistance is a concern; however, chloramphenicol, linezolid, and vancomycin remain active against common causes of GPB-BSIs.

Analysis Neutrophil-to-Lymphocyte and Monocyte-to- Lymphocyte Ratios in Pediatric Respiratory Infections

Indonesia ranks third among countries with the highest tuberculosis (TB) cases worldwide. Pneumonia also stands as a leading cause of death among infants in developing nations. The delay in diagnosing and the challenges in distinguishing TB and pneumonia have significant impacts on elevated morbidity and mortality rates. Both Neutrophil-to-Lymphocyte Ratio (NLR) and Monocyte-to-Lymphocyte Ratio (MLR) serve as inflammatory biomarkers utilized for rapid and straightforward bacteremia evaluation. This study aimed to analyze the difference between NLR and MLR in diagnosing of TB and pneumonia in children. This study was retrospective cross-sectional research utilizing secondary data at the time of initial diagnosis by a clinician as TB or pneumonia. Subjects with TB and/or pneumonia were treated at Dr. Wahidin Sudirohusodo Hospital, Makassar from January 2017 to December 2021. The research sample consisted of 150 patients with pediatric patients with pneumonia. Statistical analyses involved the Kolmogorov-Smirnov test, Mann-Whitney U test, and Receiver Operating Characteristic (ROC). This study examined NLR and MLR as supportive biomarkers for diagnosing TB and pneumonia. The NLR (AUC 0.674) and MLR (AUC 0.63) values in TB subjects were reasonably good in distinguishing between TB diagnosis and healthy subjects. The NLR (AUC 0.77) and MLR (AUC 0.787) values were effective in distinguishing pneumonia diagnosis from healthy control with better sensitivity and specificity compared to TB subjects. However, NLR (AUC 0.401) and MLR (AUC 0.384) values were not recommended to distinguish pneumonia from tuberculosis due to low AUC and extremely low sensitivity and specificity. The NLR and MLR values cannot be used to differentiate TB and pneumonia in children due to their low sensitivity and specificity.

Clinical Utility of a Multiplex PCR Panel (BioFire Joint Infection®) in the Adjustment of Empiric Antimicrobial Therapy: Experience in Pediatric Osteoarticular Infections.

This study aims to evaluate the impact of the PCR multiplex panel (BioFire JI®) on the diagnosis and management of pediatric osteoarticular infections. This retrospective study analyzed data from pediatric patients diagnosed with osteoarticular infections between January 2023 and April 2024. The effectiveness of the PCR multiplex panel in identifying pathogens was compared with traditional culture methods. In total, 50 patients were identified (66.6% male, 74% under 3 years of age). They were diagnosed as follows: septic arthritis in 46%, osteomyelitis in 26%, and septic osteoarthritis in 22%. An identifiable agent was isolated by conventional culture in 22 cases (44%). Kingella kingae was the predominant pathogen identified, accounting for 50% of cases (11/22), followed by Staphylococcus aureus (9/22). The BioFire JI® Panel PCR demonstrated a sensitivity of 93%, with a specificity of 63% when evaluated against synovial fluid culture as the reference standard. The panel identified seven additional pathogens not detected by conventional culture methods: 2/9 MSSA (22%), 1/1 S. pyogenes (100%), and 4/11 K. kingae (37%), increasing the yield by 14%. The rapid identification of pathogens facilitated timely and targeted therapeutic interventions. The PCR multiplex panel (BioFire JI®) improved the diagnosis of pediatric osteoarticular infections.

Antibiotic Resistance Pattern of Pathogens Isolated from Pediatric Patients during and after the COVID-19 Pandemic.

Background/Objectives: The present study aims to highlight the possible significant changes due to the COVID-19 pandemic in the resistance of pathogens involved in cases of pediatric infections. Methods: This study included children hospitalized in the Pediatric Intensive Care Unit, Surgery and Pediatrics from a tertiary teaching hospital, during and after the COVID-19 period (2020-2023). Results: The research included 845 samples collected during 2020-2023, from 685 pediatric patients. A total of 937 bacterial isolates were obtained, of which 509 isolates (54.32%) were Gram-negative bacteria. Around 30% of all the pathogens were multidrug-resistant (MDR), with a statistically significant increase post-pandemic, in the case of the MDR Escherichia coli strains (p < 0.05). A very high percentage of MDR Acinetobacter spp. isolates was found, with an important, but not statistically significant, increase in the post-pandemic period. The highest percentage of the MDR Gram-positive pathogens was registered in the case of S. aureus strains (31.80%). Over 20% of the Coagulase-negative Staphylococci (CoNS) strains isolated between 2020 and 2023 were MDR, with an important increase in the post-COVID-19 period. The proportion of carbapenem-resistant Gram-negative pathogens significantly decreased in the post-COVID-19 period compared with the COVID-19 period (p < 0.05), especially in the case of the Klebsiella spp. strains. Conclusions: Our findings revealed the increase in the post-COVID-19 period of the prevalence of MDR strains of Acinetobacter spp., CoNS, and Escherichia coli isolated in pediatric patient samples and a significant decline in the trend of the carbapenem-resistant Gram-negative pathogens, which may be due to the testing rate and to the specific pathology of the pediatric patients hospitalized in the two periods.

Triple broadly neutralizing antibody (bnAb) combination therapy: a cure for pediatric HIV?

Abstract Background In 2022, UNAIDS estimated out of the 1.7 million children living with HIV, only 57.1% had access to antiretroviral therapy (ART). Though ART has significantly decreased HIV-associated morbidity and mortality, it cannot eliminate the latent viral reservoir. Consequently, most people living with HIV demonstrate viral rebound when ART is interrupted. There is therefore a critical need for alternative therapeutic to achieve long term ART free viral control. Broadly neutralizing antibodies (bnAb) have shown promising results in preclinical and clinical studies, but their potential efficacy is limited by the emergence of escape variants, especially with monotherapy. We previously tested the neutralizing and non-neutralizing functions of different bnAb combinations and identified a triple bnAb combination that showed robust neutralization potency and breadth, as well as non-neutralizing functions. In this project, we investigated the impact of combination bnAb therapy on viral rebound in SHIV infected infant rhesus macaques (RMs). Methods Ten infant rhesus macaques were orally challenged with SHIV.C.CH505 at 4 weeks of age. Oral challenge is a well-established method that is used to mimic breastmilk transmission of HIV, which contributes to almost 50% of pediatric HIV infections every year. A triple bnAb combination of simianized 3BNC117 (CD4 binding site), PGDM1400 (V2 glycan dependent), and PGT151 (interface) was subcutaneously administered twice at 40 mg/kg of each antibody. The initial infusion was administered at ART initiation (8 weeks post-infection) while the second infusion with administered at the time of analytical treatment interruption (ATI) (49 weeks post-infection). RMs were monitored weekly from the beginning of infection until 12 weeks post-ATI. Enzyme-linked Immunosorbent Assay (ELISA) was used to monitor plasma concentrations of each bNab and Env-specific IgG binding responses. Results Env-specific antibody binding levels against HIV envelope proteins gp120 and gp41 peaked in plasma 8 weeks after infection. The antibody levels then slightly decreased during ART and increased again after viral rebound following ATI. BnAb plasma concentrations peaked 1-2 weeks after each bnAb infusion, then slowly declined. After the initial infusion, all RMs had undetectable levels of 3BNC117 and PGT151 by 8 weeks post initial infusion, and only 2/10 RMs had detectable PGDM1400 levels. All animals experienced viral rebound following ATI.). Importantly, the average time to virus rebound (7 weeks, range 3-10 weeks) was significantly longer than a s control group of RMs without any immune-based intervention (~2.5 weeks). By the time of viral rebound, most animals had undetectable plasma levels of 3BNC117, PGDM1400 or PGT151. However, in some animals, rebound occurs when passively administered antibodies were still detectable, suggesting the emergence of bnAb resistant variants. Conclusion Passive immunization with a triple-bnAb combination of 3BNC117, PGT151 and PGDM1400 was associated with delayed viral rebound, but more investigation is needed to understand the potential role of this strategy in the HIV therapeutic portfolio. Future work will investigate the sensitivity of the rebound viruses to the bnAb combination to evaluate the contribution of bnAb escape to viral rebound.

Distribution and seasonality of viral respiratory infections in pediatric oncologic patients in a tropical country

Abstract Background Comprehension of the distribution and seasonality viral respiratory infections pediatric oncologic patients in tropical localities remains poor. Due to lack mandatory report of all viruses and limitations in access to molecular biology techniques there is currently few data published on this topic. We report the distribution and seasonality of pediatric viral respiratory infections at a tertiary care oncological hospital in Guayaquil, Ecuador. Methods The laboratory database with results of real time PCR panel (Biofire® respiratory panel 2.1) from January to December 2021 was reviewed to collect the relative frequency and seasonality of identifiable viral infections in pediatric (ages &amp;lt; 18 years) patients. The frequency of infection according to sample characteristics including sex and age was compared using chi square test with a significance of 0.05. The frequency of detection was organized per month within the year. Percentage of coinfections was also determined. Results Out of 217 included PCR results, 143 (65.8%) tested positive for detectable viral organisms. Mean age was 7.3 years SD 4.8 years. The infection frequency for girl samples was higher than that of boy samples, X2 (1, N=217) = 4.16, p 0.041. The relation between age groups and the frequency of infection was not statistically significant X2 (2, N=217) = 5.24, p 0.073. The most prevalent viruses included Rhinovirus/Enterovirus 53 cases (relative frequency 37.0%), Parainfluenza virus 3 42 cases (relative frequency 29.3%) and Respiratory syncytial virus 19 cases (relative frequency 13.2%). Rhinovirus/Enterovirus, Paramyxovirus and Adenovirus respiratory infections occurred throughout the year while other respiratory viruses including Coronaviruses showed a higher detection rate during the rainy season (December – April). A total of 13 (5.9%) patients were coinfected with two up to four viruses. The most common combination was Parainfluenza virus 3 with Rhinovirus/Enterovirus. No bacterial targets were detected. Conclusion Larger and more complex studies are necessary to understand the burden of viral respiratory infections in pediatric oncological patients. In Ecuador, detection was higher in girls and school aged children. Rhinovirus/Enterovirus, Paramyxovirus and Adenovirus were present all year long while seasonality was common for other viruses following dry/rainy season pattern in the region. More understanding of seasonality will aim for preventive measures during more difficult months and to distribute resources accordingly. Figure 1. Seasonality of respiratory viral infections.

The Impact of Tele-Stewardship on Rural Antibiotic Prescribing Practices

Abstract Background Antibiotic prescribing for children is highest in rural areas. Tele-stewardship allows for implementation of antimicrobial stewardship (AS) via telecommunication with providers. There has been limited research on the effectiveness of tele-stewardship in the outpatient setting. In this study, we address the need for better AS in rural areas by developing, implementing, and evaluating AS interventions using tele-stewardship. Methods We employed bundled outpatient AS implementation strategies in rural pediatric primary care (PC) clinics and emergency departments (EDs) affiliated with Vanderbilt University Medical Center (VUMC) using tele-stewardship. The bundle includes (1) patient/guardian educational materials, (2) antibiotic use commitment posters (3) provider education through quarterly teaching pearls on common pediatric infections, communication skills training (DART modules), app-based microlearning modules (QuizTime), and implicit/explicit bias education and (4) quarterly audit and feedback with peer comparison on guideline-concordant antibiotic use. Participants are pediatric prescribers (physician, physician assistant, nurse practitioner). We compared antibiotic prescription data for children &amp;lt;18 years collected during the “baseline” period (Jan-Dec 2022) to the intervention period (Jan-Sept 2023). Two academic urban primary care clinics and one academic urban ED at which the interventions were not implemented were included as “control” sites. The primary outcome is percent of all encounters that result in an antibiotic prescription. Pre- and post-intervention data were analyzed in aggregate (not at the provider-level). Significance was determined via calculating a 95% confidence interval (CI) for the difference of proportions. Results To date, there have been 140,077 PC patient encounters (98,409 baseline and 41,065 intervention) and 94,205 ED encounters (61759 baseline and 32,446 intervention) across all sites. Change from baseline to intervention periods in academic PC sites was 0.9 percentage points (95% CI 0.556 to 1.243; 6.6% baseline, 7.5% intervention) while change in rural intervention sites was -1.05 percentage points (95% CI -0.409 to -1.667; 11.8% baseline, 10.75% intervention; Figure 1a). Only 1 of 3 rural EDs had a decrease in percent of encounters with an antibiotic prescription (Figure 1b). Overall the academic ED showed a 3.1 percentage point increase (95% CI 2.430 to 3.769; 18.0% baseline, 21.1% intervention) while the rural sites showed a 1.0 percentage point increase (95% CI -0.817 to 2.817; 24.2% baseline, 25.2% intervention). Conclusion Interim analysis shows that bundled implementation strategies using tele-AS led to significantly decreased overall antibiotic use in rural primary care clinics compared to urban academic control sites. The study is ongoing and will continue to evaluate outcomes over a longer intervention period to reduce seasonal bias.

Proteomic profiling of the local and systemic immune response to pediatric respiratory viral infections.

We describe the first proteomic profiling of the lower airway and blood in critically ill children with severe viral lower respiratory tract infection (vLRTI). From tracheal aspirate (TA), we defined a proteomic signature of vLRTI characterized by increased expression of interferon signaling proteins and decreased expression of proteins involved in immune modulation including FABP and MIP-5. Using machine learning, we developed a parsimonious diagnostic classifier that distinguished vLRTI from non-infectious respiratory failure with high accuracy. Comparative analysis of paired TA and plasma specimens demonstrated limited concordance, although the interferon-stimulated protein ISG15 was significantly upregulated with vLRTI in both compartments. We further identified TSG-6 and CRP as airway biomarkers of bacterial-viral coinfection, and viral load analyses demonstrated positive correlation with interferon-related protein expression and negative correlation with the expression of neutrophil activation proteins. Taken together, our study provides new insight into the lower airway and systemic proteome of severe pediatric vLRTI.

An altered natural killer cell immunophenotype characterizes clinically severe pediatric RSV infection.

Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV+ children) develop respiratory failure requiring intensive care, but immune mechanisms distinguishing severe pediatric RSV infection are not fully elucidated. Natural killer (NK) cells are key innate immune effectors of viral host defense. In this study of 47 critically ill RSV+ children, we coupled NK cell immunophenotype and cytotoxic function with clinical parameters to identify an NK cell immune signature of severe pediatric RSV disease. Airway NK cells were increased in intubated RSV+ children with severe hypoxemia and prolonged duration of mechanical ventilation and were correlated with clinical severity scores. Peripheral blood NK cells were decreased in RSV+ patients and had altered activating receptor expression, with increased expression of CD69 and decreased expression of NKG2D. Ex vivo, circulating NK cells from RSV+ patients exhibited functional impairment characterized by decreased cytotoxicity as well as aberrant immune synapse assembly and lytic granule trafficking. NK cell frequency and phenotype correlated with clinical measures that defined disease severity. These findings implicate a role for NK cells in mediating RSV immunopathology and suggest that an altered NK cell immunophenotype is associated with severe RSV disease in young children.

A review of clinical and preclinical data supporting a role for resveratrol in the treatment of common respiratory tract pathogens

Respiratory infections are a relevant issue during infancy and childhood, constituting a major source of morbidity and imposing a substantial burden on healthcare systems. Conditions such as bronchiolitis, pneumonia, and influenza exemplify the gravity of these infections among pediatric populations. In the context of this health challenge, resveratrol, a naturally occurring polyphenolic antioxidant has emerged as a focal point of extensive research, known for its antioxidant, anti-inflammatory, and antimicrobial properties. This comprehensive review delves into the compound's extensive antimicrobial activities against a diverse range of bacteria and viruses, both as a standalone agent and in combination with conventional antibiotics. This compound exhibits notable antiviral activity against viruses implicated in severe respiratory infections, offering a potential therapeutic avenue. By exploring the antiviral mechanisms and highlighting the anti-inflammatory potential of resveratrol, this comprehensive overview contributes to a deeper understanding of its applicability in mitigating the complexities associated with pediatric respiratory infections.

Importance of risk adjusting central line-associated bloodstream infection rates in children.

Central line-associated bloodstream infection (CLABSI) is one of the most prevalent pediatric healthcare-associated infections and is used to benchmark hospital performance. Pediatric patients have increased in acuity and complexity over time. Existing approaches to risk adjustment do not control for individual patient characteristics, which are strong predictors of CLABSI risk and vary over time. Our objective was to develop a risk adjustment model for CLABSI in hospitalized children and compare observed to expected rates over time. We conducted a prospective cohort study using electronic health record data at a quaternary Children's Hospital. We included hospitalized children with central catheters. Risk factors identified from published literature were considered for inclusion in multivariable modeling based on association with CLABSI risk in bivariable analysis and expert input. We calculated observed and expected (risk model-adjusted) annual CLABSI rates. Among 16,411 patients with 520,209 line days, 633 patients experienced 796 CLABSIs. The final model included age, behavioral health condition, non-English speaking, oncology service, port catheter type, catheter dwell time, lymphatic condition, total parenteral nutrition, and number of organ systems requiring ICU level care. For every organ system receiving ICU level care the odds ratio for CLABSI was 1.24 (95% CI 1.12-1.37). Although not statistically different, observed rates were lower than expected rates for later years. Failure to adjust for patient factors, particularly acuity and complexity of disease, may miss clinically significant differences in CLABSI rates, and may lead to inaccurate interpretation of the impact of quality improvement efforts.

The predictive value of PCT, SP-D and 8-iso-PGF2 α for the development of severe pneumonia in children

Background: To investigate the predictive value of predictive value of procalcitonin (PCT), 8-iso-prostaglandin F2α (8-iso-PG-F2α) and pulmonary surfactant-associated protein D (SP-D) for the development of severe pneumonia in children. Methodology: Children with severe pneumonia were selected as the pneumonia group, and children with non-pulmonary respiratory diseases were selected as the control group. PCT, 8-iso-PGF2α, and SP-D were compared between the pneumonia group and the control group at admission; PCT, 8-iso-PGF2α, SP-D, and Acute Physiology and Chronic Health Evaluation (APACHE-II), Pediatric Critical Illness Score (PCIS) and Clinical Pulmonary Infection Score (CPIS) scores were compared between children with severe pneumonia with different pathogen infection types and different prognostic outcomes; and the correlation between APACHE-II, CPIS, and PCIS scores and PCT, 8-iso-PGF2α, and SP-D levels was analysed in children with severe pneumonia. Results: PCT, 8-iso-PGF2α and SP-D in pneumonia group were higher than those in control group. PCT, 8-iso-PGF2α, SP-D, APACHE-II, CPIS, and PCIS were lower in good prognosis children than in poor prognosis children. APACHE-II, CPIS, and PCIS scores were positively correlated with PCT, 8-iso-PGF2α, and SP-D levels in children with severe pneumonia (P &lt; 0.05). Conclusion: PCT, SP-D and 8-iso-PGF2α levels relate to pathogen type, illness severity and prognosis in children with severe pneumonia. They can aiding early evaluation. Keywords: severe pneumonia in children; procalcitonin; 8-isoprostane F2α; pulmonary surfactant-associated protein D; disease assessment.

The impact of the COVID-19 pandemic on RSV outbreaks in children: A multicenter study from China

ObjectiveThe aim of the study is to describe the season of RSV prevalence in China during the COVID-19 pandemic. MethodsThis multicenter retrospective study analyzed the epidemiology of pediatric RSV infections and the possible factors contributing to its variations in China from January 1, 2019, to October 31, 2022. ResultsA total of 872,565 children were included. During the pandemic, RSV detection rate increased across various regions, including South China, East China, Central China, and Northeast China. From 2019 to 2021, the detection rates of RSV showed an increasing trend among children aged <1 year, 1–2 years, and 3–5 years, but decreased in 2022. Among those tested positive for RSV, the proportion of children under 1 year old significantly decreased during the pandemic. The spring season of RSV in China in 2020 was shortened, and most regions experienced a summer season of RSV in 2021. This shift led to a year-round RSV outbreak throughout 2021. After April 2022, RSV positive rate significantly decreased, and no clear seasonal pattern was observed. ConclusionOur study found that the COVID-19 pandemic has disrupted the seasonal pattern of RSV outbreaks in China, leading to increased RSV positive rate and off-season outbreaks.

A-260 Mapping pediatric urinary tract infections: trends, prevalence and sensitivity to antimicrobials

Abstract Background Urinary tract infections (UTIs) rank among the most prevalent bacterial infections in pediatric populations, with neonates being particularly susceptible. Moreover, UTIs have a propensity for recurrence, posing ongoing health challenges. Prompt diagnosis of pediatric UTIs is crucial for timely and effective treatment, averting potential long-term complications. While clinical signs often suggest UTI diagnosis, additional tests like urinalysis and urine culture are vital to identify the causative pathogen and its antibiotic sensitivity. This study aims to quantify microorganism prevalence in positive pediatric urine tests and assess their antimicrobial resistance profiles. The purpose is, therefore, to offer scientific basis so that there is greater agility in establishing the diagnosis of UTIs in children and indicating the best antibiotic to be used empirically to prevent late consequences. Methods Between January and December 2019, a cross-sectional study was carried out with urine samples from children and adolescents collected in the database of the Clinical Analysis Laboratory of Cuiabá - MT in 2019. Only records of samples collected in the study were included in the study. laboratory of patients of both sexes, age range 1 month to 15 years. Bacterial analyzes were classified according to Gram positive, Gram negative (glucose fermenters or non-fermenters) and the sensitivity profile was standardized according to the Clinical and Laboratory Standards Institute (2019). The data were subjected to descriptive statistical analysis. Results Of the 532 positive urine samples from pediatric patients, enterobacteria were responsible for 435 (81.76%) with E. coli (64.1%) and Proteus mirabilis (15.8%) being the most isolated bacteria, in relation to Gram-positive bacteria 64 (12.03%) main bacteria was Enterococcus faecalis (81.2%) and non-glucose fermenters for 33 (6.2%) corresponding to Pseudomonas aeruginosa. E. coli, with 279 cases, was the most frequently isolated microorganism, representing (64.1%) of the cases. Females were the most affected, in 83.5% there was growth of Enterobacteria, in the Pseudomonas aeruginosa group, 51.5% of cases were female. and in Gram+ girls represented 56.2%. In those tested only for E. coli, the highest sensitivity was observed in fosfomycin (97.82%). Enterobacteriaceae showed high susceptibility to meropenem (99.8%), ertapenem (99.8%), ceftriaxone (93.8%), and ceftazidime (93.6%), but exhibited considerable resistance to sulfamethoxazole/trimethoprim (35.5%), amoxicillin (33.4%) and ampicillin (29.2%). Pseudomonas aeruginosa and gram positive bacteria were sensitive to all antibiotics tested. Conclusions The data indicate that E. coli continues to be the predominant agent in pediatric UTIs, particularly affecting females and the very young age group &amp;lt; 3 years. Regarding sensitivity profiles, bacteria were more sensitive to carbapenems and aminoglycosides. Early diagnosis is crucial to preventing long-term complications associated with UTIs in children. Consequently, this research provides a scientific basis for faster UTI diagnosis and empirical antibiotic selection in pediatrics, which may prevent late adverse outcomes.