Infected Infants Research Articles

Clinical features and risk factors of Klebsiella pneumoniae infection in premature infants: a retrospective cohort study.

With the continuous advancement of modern medical technology, the survival rate of premature infants has significantly increased. Klebsiella pneumoniae (K. pneumoniae) is one of the most common pathogens causing neonatal infections, particularly posing a serious risk to premature infants. This study aimed to analyze the clinical characteristics, antibiotic susceptibility profiles, and treatment outcomes of K. pneumoniae infections in these infants. We retrospectively compared cases of K. pneumoniae infection in premature and term infants admitted in a tertiary hospital from January 2017 to December 2022 in China. Clinical and microbiological characteristics were evaluated. Data analysis was performed using the Statistical Package for the Social Sciences (SPSS), with statistical significance defined as P < 0.05. We enrolled 166 premature infants and 68 term infants. In premature infants, fetal distress, patent ductus arteriosus, patent foramen ovale, enteritis, anemia, hypoproteinemia, bloodstream infections, abdominal infection, mechanical ventilation, nasogastric feeding, drainage tube, parenteral nutrition, and prior exposure to carbapenem antibiotics were identified as significant risk factors for K. pneumoniae infections in univariate analysis. Furthermore, septic shock, bloodstream infections, abdominal infections, indwelling catheters, drainage tubes, parenteral nutrition, and previous exposure to glycopeptide antibiotics were significantly correlated with mortality. Independent risk factors for K. pneumoniae infections in premature infants included fetal distress (OR: 3.702, [95% CI: 1.056-12.986], P = 0.041), enteritis (OR: 4.434, [95% CI: 1.066-18.451], P = 0.041), anemia (OR: 4.028, [95% CI: 1.550-10.466], P = 0.004), bloodstream infections (OR: 1.221, [95% CI: 0.061-1.802], P = 0.022), mechanical ventilation (OR: 4.974, [95% CI: 1.685-14.685], P = 0.004) and prior exposure to carbapenem antibiotic (OR: 14.738, [95% CI: 2.393-90.767], P = 0.004). Additionally, abdominal infections (OR: 8.598, [95% CI: 2.000-36.957], P = 0.004) and indwelling catheters (OR: 7.698, [95% CI: 0.998-59.370], P = 0.050) were positive predictors of mortality. K. pneumoniae isolates exhibit a notable prevalence of infection, poor treatment outcomes, and elevated resistance in preterm neonates. These findings enhance our understanding of K. pneumoniae infections and their association with clinical outcomes among premature infants.

A triad of gut dysbiosis, dysregulated immunity, and 'leaky' gut characterize HCMV associated neonatal cholestasis.

Gut microbiome dysbiosis and related immune dysfunction have been associated with the pathogenesis of Human Cytomegalovirus (HCMV) infection in infants with neonatal cholestasis (NC) as previously reported by us. However, the interaction of a perturbed microbiome, HCMV infection, and dysregulated immunity leading to exacerbation of disease severity has not been investigated so far. In this study, we examined the association of gut microbiome, host inflammatory and homeostatic markers that are likely to govern increased pathogenesis of NC in HCMV infected IgM positive infants (N = 15) compared to IgM negative (N = 15) individuals. Stool samples of HCMV infected infants and age-matched healthy controls (N = 10) were assessed for gut bacteria-derived metabolites like short-chain fatty acids (SCFAs), Lipopolysaccharide (LPS), cytokines and markers of gut barrier integrity. Data were correlated with previously determined gut microbiome composition and frequency of immune cell subsets. Finally, validation of clinical potential was undertaken by principal component analysis (PCA) of integrated data to delineate the spectrum of clinical pathology. Significantly lower levels of SCFAs and elevated fecal levels of soluble inflammatory mediators were observed in IgM positive HCMV infected infants. Further, increased plasma LPS levels and markers of gut permeability, suggestive of microbial translocation due to a 'leaky gut' were observed in HCMV infected IgM positive group. PCA of integrated data revealed clearly disparate profiles representative of IgM positive, IgM negative, and uninfected healthy states. Our results suggest the utility of an integrated approach involving dysregulated microbiome-immune axis for gaining a better understanding of pathogenesis associated with HCMV infection in NC.

The Impact of Palivizumab for Respiratory Syncytial Virus Prophylaxis on Preschool Childhood Asthma

Background: The respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in infants and is associated with an increased risk of asthma development. Palivizumab, an RSV prophylactic, reduces RSV-related hospitalizations in high-risk infants, but its impact on long-term asthma outcomes remains unclear. This study compares asthma-related healthcare utilization in preschool children born prematurely between those who received Palivizumab (the Prophylaxis (+) group) and those who did not (the Prophylaxis (–) group). Methods: This nationwide, population-based retrospective cohort study utilized data from Clalit Healthcare Services in Israel. The study included children born between 32 + 6 and 34 + 6 weeks of gestational age from 2011 to 2018. Descriptive analysis, univariate analysis, and multivariate logistic regression were performed to compare the Prophylaxis (+) and the Prophylaxis (–) groups. Results: In total, 4503 children were included, with 3287 in the Prophylaxis (+) group and 1216 in the Prophylaxis (–) group. Palivizumab administration was associated with reduced hospitalizations for RSV bronchiolitis (1.8% vs. 3.3%, p = 0.003). However, no significant differences were observed in multivariate analysis for long-term asthma outcomes, including asthma diagnosis (OR = 1.04, CI = 0.84–1.30, p = 0.7) or emergency department visits for asthma (OR = 0.79, CI = 0.54–1.17, p = 0.2). Similarly, Palivizumab administration was not associated with the purchase of short-acting beta-agonists (OR = 1.14, 95% CI 0.98–1.32, p = 0.084), inhaled corticosteroids (OR = 1.1, CI = 0.93–1.32, p = 0.3), or oral corticosteroids (OR = 1.09, CI = 0.94–1.26, p = 0.3). Conclusions: While Palivizumab effectively reduces RSV acute bronchiolitis in preterm infants, it does not significantly impact long-term preschool asthma-related healthcare utilization.

Risk Factors of the Severity of COVID-19 Infection in Infants

Background: The global COVID-19 crisis has profoundly affected populations worldwide. While it is widely accepted that older individuals are at greater risk of severe illness, data indicate that in newborns and infants, the disease is generally not fatal. Objectives: This cross-sectional study aimed to examine the roles of laboratory tests and clinical symptoms in determining the severity of COVID-19 infection in infants younger than three months. Methods: This study included all infants less than three months old with positive PCR tests for COVID-19 admitted to the Children's Medical Center between October 2020 and March 2022. We analyzed the association between disease severity and clinical symptoms, as well as laboratory findings. Results: Sixty-four neonates and infants under three months of age with COVID-19 participated in the study. Our findings suggest that lower birth weight and gestational age are associated with increased disease severity. Infants with underlying medical conditions were found to have a higher risk of reaching stage IIb or greater severity. Among laboratory and clinical findings, only white blood cell (WBC) count and cough symptoms showed a significant correlation with disease severity. Conclusions: Clinical evaluations, along with factors such as birth weight, gestational age, and underlying conditions, appear more effective in guiding decision-making for COVID-19 severity in infants. Further studies are necessary to explore the influence of these factors on COVID-19 severity in this age group.

Genomic perspectives on foodborne illness

Whole-genome sequencing of bacterial pathogens is used by public health agencies to link cases of food poisoning caused by the same source of contamination. The vast majority of these appear to be sporadic cases associated with small contamination episodes and do not trigger investigations. A "contamination episode" refers to one or more contamination events from a single source over a period of time. We examine clusters of sequenced clinical isolates of Salmonella, Escherichia coli, Campylobacter, and Listeria that differ by only a small number of mutations (SNPs) to identify features of the underlying contamination episodes. These analyses provide additional evidence that the youngest age groups have greater susceptibility to infection by Salmonella, E. coli, and Campylobacter than older age groups. This age bias is weaker for the common Salmonella serovar Enteritidis than Salmonella in general. A large fraction of the contamination episodes causing sickness appear to have a long duration. For example, 50% of the Salmonella cases are in clusters that persist for almost 3 y. For all four pathogen species, the majority of the cases were part of genetic clusters with illnesses in multiple states and likely to be caused by contaminated commercially distributed foods. Salmonella infections in infants under 3 mo are predominantly acquired from the same contaminated food, pet food, or environmental sources as older individuals, rather than infant formula contaminated during production.

Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus.

Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection mitigated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated antiapoptosis pathway as a target to battle severe RSV disease in infants.

Risk factors for and short-term prognosis of intrauterine infection in preterm infants.

To identify the risk factors for and short-term prognosis of intrauterine infection (IUI) in preterm infants. We retrospectively collected clinical data regarding preterm infants (28+0-36+6 weeks of gestational age) with IUI from the neonatal intensive care unit of our hospital between June 2017 and June 2022. The pathologic characteristics of the infants were classified using the Redline criteria, and the resulting groups were compared with respect to their clinical characteristics, indicators of infection, complications, and mortality rates. Three hundred thirty (78.1%) of the 422 enrolled neonates showed signs of histologic IUI; 51.8% showed histologic chorioamnionitis alone, and 48.2% showed both histologic chorioamnionitis and funisitis. The independent risk factors identified for IUI were maternal prenatal invasive manipulation, premature rupture of membranes (>18 hours before labor), and prenatal C-reactive protein concentration. The infants with IUI showed higher incidences of respiratory distress syndrome, bronchopulmonary dysplasia, retinopathy of prematurity, and prolonged mechanical ventilation. Low gestational age and low birth weight of preterm infants were significantly associated with a higher incidence of histologic IUI, more severe inflammation, and a higher incidence of complications. Histologic IUI is associated with high complication and mortality rates in preterm infants, as is an increasing severity of inflammation.

Characterization of a Highly Virulent Klebsiella michiganensis Strain Isolated from a Preterm Infant with Sepsis.

Klebsiella michiganensis is an opportunistic pathogen that causes an increasing number of serious infections. This study aimed to investigate the etiology of the severe clinical symptoms of sepsis in preterm infants and the characterization of K. michiganensis isolates. Whole-genome sequencing (WGS) was performed on three strains isolated from an infected preterm infant. Additionally, the genomic sequences of 534 K. michiganensis strains were obtained from the NCBI database. To gain deeper insights into these strains, we utilized the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Clusters of Orthologous Groups (COG), and Pathogen Host Interactions (PHI) database annotation tools for comprehensive gene function analyses. Moreover, the multilocus sequence typing (MLST), EasyCGtree, and virulence factor database (VFDB) were employed to determine the sequence types (STs), construct phylogenetic trees, and identify potential virulence factors. Sequence analysis found that the three isolated strains had identical sequence characteristics and did not correspond to any of the known ST types. Virulence factor analysis revealed that the three strains harbored mrkABCDFHIJ, fimABCDEFGHIK, entABCDEFS, fepABCD, and capsule genes. These virulence factors are likely to play crucial roles in enhancing adhesion and metabolic capabilities, resisting phagocytosis (inducing immune cell damage), and ultimately contributing to prolonged bacteremia. The phylogenetic tree and comparative genomics of virulence factors showed the genetic and virulence factor diversity of the currently reported K. michiganensis strains. We identified a novel strain of K. michiganensis that exhibits high virulence and leads to severe septicemia phenotypes in preterm infants. Furthermore, comparative genomic analysis of previously reported K. michiganensis strains revealed the existence of three clades. This comprehensive analysis provides novel insights into the genetic relationships and virulence factor profiles of diverse strains of K. michiganensis. In future, it will be necessary to investigate the concept of the high virulence of K. michiganensis to determine the treatment method.

Evaluation of adenoviral vector Ad19a encoding RSV-F as novel vaccine against respiratory syncytial virus

Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infections in infants and toddlers. Since natural infections do not induce persistent immunity, there is the need of vaccines providing long-term protection. Here, we evaluated a new adenoviral vector (rAd) vaccine based on the rare serotype rAd19a and compared the immunogenicity and efficacy to the highly immunogenic rAd5. Given as an intranasal boost in DNA primed mice, both vectors encoding the F protein provided efficient protection against a subsequent RSV infection. However, intramuscular immunization with rAd19a vectors provoked vaccine-enhanced disease after RSV infection compared to non-vaccinated animals. While mucosal IgA antibodies and tissue-resident memory T-cells in intranasally vaccinated mice rapidly control RSV replication, a strong anamnestic systemic T-cell response in absence of local immunity might be the reason for immune-mediated enhanced disease. Our study highlighted the potential benefits of developing effective mucosal against respiratory pathogens.

Supramolecular Self-Assembled Hydrogel for Antiviral Therapy through Glycyrrhizic Acid-Enhanced Zinc Absorption and Intracellular Accumulation.

Respiratory syncytial virus (RSV) is a common pathogen that causes respiratory infections in infants and children worldwide, significantly impacting hospitalization rates in this age group. Zinc ions are considered to have broad-spectrum antiviral potential against RNA viruses, including RSV. However, poor organism absorption and low intracellular accumulation of zinc require repeated high-dose supplementation, which may lead to unnecessary toxic side effects. In this research, a Zn2+-mediated glycyrrhizinic acid (GA)-based hydrogel (ZnGA Gel) was introduced and potentially developed to be a clinically available drug candidate for RSV therapy. ZnGA Gel was fabricated based on the cooperation of two potential RSV inhibiting molecules (Zn2+ and GA), where Zn2+ promoted self-assembly of GA and reduced its gel concentration and GA promoted zinc absorption and distribution in lung tissue in vivo. The facile construction of supramolecular hydrogel by the self-assembled coordination complex made it an injectable, temperature-sensitive, and pH-responsive controlled-release drug delivery for Zn2+. Most importantly, GA was observed to enhance organism absorption and intracellular accumulation of Zn2+ and was identified as a zinc ionophore for the first time. GA can colonize on the cell membrane and disturb cell membrane potential, resulting in an enhanced cell membrane permeability. In the presence of GA, more than 4.7-fold increasing Zn2+ concentrations materialized in the intracellular cytoplasm, compared to Zn2+ alone administration. This intracellular Zn2+ accumulation directly boosted the antiviral activities through improved inhibition of RSV replication-associated proteins and significantly inhibited RSV replication. Oral administration of ZnGA Gel on the RSV-infected mice model achieved an ideal therapeutic effect by effectively lowering viral load in the lungs, alleviating lung injury symptoms, and reducing inflammatory cell infiltration at pathological sites. The mechanism involved the inhibition of RSV replication-related proteins, aligning with our in vitro results. Additionally, ZnGA Gel had demonstrated biocompatibility, and reasonable supplementation of zinc was acceptable and effective for infants and children in clinical practice. Hence, the ZnGA Gel developed by us holds promise as an effective anti-RSV medicine in the future.

Rapid health technology assessment to inform policy: a case study with respiratory syncytial virus

Abstract Background Respiratory syncytial virus (RSV) can cause severe acute respiratory tract infection in infants and older adults. However, until recently, no immunisation interventions were available to reduce the burden of RSV disease in the general population. New health technologies have now been authorised in Europe for infants (a long-acting monoclonal antibody (nirsevimab) and a maternal vaccine (RSVpreF)), and two vaccines for adults aged ≥60 years (RSVPreF3 and RSVpreF). A rapid health technology assessment (HTA) was requested by the Irish Department of Health to support an interim decision on RSV immunisation. Methods The rapid HTA commenced in January 2024, and comprised description of technology, a summary of international practice, national and international epidemiology and burden of disease, and a costing analysis. The summary of international practice (including underpinning evidence) was undertaken rather than a systematic review of effectiveness and safety due to the rapidly changing evidence base and short timeline within which information was required. Results While new recommendations regarding immunisation against RSV are emerging internationally in response to recently authorised technologies, implementation and funding strategies are not currently widespread. Compared with a full HTA, a rapid HTA enabled an efficient and flexible approach to producing a high quality evidence synthesis to inform a temporary policy decision, taking approximately 6 months to complete rather than 12 months or longer. A full HTA is planned to inform long-term decision-making on this topic, but would not have been feasible to inform an interim decision. Conclusions This rapid HTA will inform a temporary decision on immunisation policy for a single RSV season in Ireland. Conducting a rapid HTA prior to a full HTA has enabled timely decision-making, with implications for Ireland’s national healthcare system and people at risk of severe RSV-related disease. Key messages • Innovations in immunisation against RSV are leading to changes in policy across Europe. • Rapid HTA can support timely, evidence-based public health decision-making in a fast-evolving field.

New advances in RSV: Is prevention attainable?

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI), hospitalization, and mortality in infants and young children globally. The greatest burden of severe disease and mortality occurs in low-middle income countries (LMICs), with large and vulnerable childhood populations. The highest rates of RSV-hospitalization occur in healthy-term infants under 3 months of age. Preterm infants, children with chronic lung disease of prematurity, Down's syndrome, congenital heart disease, or immunodeficiency also have a higher risk of severe RSV-LRTI. Early-life RSV-LRTI has also been associated with chronic sequelae, including recurrent LRTI, recurrent wheezing, asthma, and lung function impairment. A RSV pre-fusion (F) maternal vaccine and long-acting monoclonal antibody (nirsevimab) have been licensed for the prevention of RSV-LRTI in infants and young children. Studies show high efficacy and effectiveness particularly for preventing severe RSV-LRTI. Maternal RSV vaccine given at 24-36 weeks of pregnancy was effective in preventing RSV medically attended LRTI and severe RSV-LRTI through 6 months after birth in a phase 3 study conducted in 18 countries over two RSV seasons. Vaccination was safe with no significant difference in adverse events between infants born to mothers who received RSV preF vaccine compared to placebo. A numerical imbalance in preterm births that occurred predominantly in South Africa, unrelated to vaccine timing or gestational age at vaccination and unassociated with mortality, coincided with COVID-19 delta and omicron waves. Nirsevimab, given as a single dose prior or during the RSV season, had high efficacy in preventing RSV-LRTI hospitalization in infants in preterm and in full-term infants, as well as in young children with underlying conditions through 150 days post administration in phase 2 and 3 trials. High effectiveness against hospitalization or severe disease in infants and in at-risk children up to 2 years of age has also been reported in several countries where implementation has occurred. RSV-LRTI is now a preventable disease in infants and young children. Rapid implementation of these highly effective interventions has occurred in many high-income countries, but access remains very limited in LMICs. Access to such RSV preventive interventions is urgently needed for all children to strengthen child health and promote global equity.

Vaccination against respiratory syncytial virus (RSV)-For the protection of infants and older adults

Respiratory syncytial virus (RSV) is afrequent cause of respiratory infections in all age groups. Infections in infants and older adults frequently result in severe disease and complications. There is no specific antiviral treatment against RSV. The characterization of the structure of the fusion (F) protein in its immunogenic prefusion conformation has enabled the development of novel vaccines directed against the prefusion protein as the antigen. These include an adjuvanted monovalent vaccine (Arexvy) and anonadjuvanted bivalent vaccine (Abrysvo). Both are approved and indicated for use in older adults, in whom they have been shown to be over 80% effective in the protection against symptomatic RSV infections and associated lower respiratory tract diseases. Abrysvo is approved for use in pregnancy to protect the newborn through the transplacental transfer of high-titer maternal antibodies. The vaccine has been shown to have an efficacy of over 80% in the first 3 months of life to protect the infant from severe RSV-associated lower respiratory disease but slightly deceases after an age of 6 months. The clinical studies demonstrated the safety of the vaccines in both adults and pregnant women. The rate of undesired side effects was low in all studies and severe side effects were very rare. The new vaccines are efficacious new tools to prevent RSV-associated disease and complications in high-risk groups. For infants, an alternative strategy can be passive immunization with monoclonal antibodies, including the recently developed nirsevimab, which has also shown high efficacy.

The Effectiveness of Heat-Killed Pediococcus acidilactici K15 in Preventing Respiratory Tract Infections in Preterm Infants: A Pilot Double-Blind, Randomized, Placebo-Controlled Study.

Preterm infants discharged from the neonatal intensive care unit (NICU) have a risk of severe viral respiratory tract infections (RTIs). Researchers have recently reported the potential use of postbiotics to decrease RTIs in young children. However, the safety and efficacy of postbiotics for preventing RTIs in preterm infants is not yet established. We conducted a pilot double-blind, randomized, placebo-controlled study of the heat-killed lactic acid bacterium Pediococcus acidilactici K15 in 41 preterm infants born at <36 weeks of gestation and discharged from the NICU at Chiba University Hospital. Following once-daily K15 or placebo treatment for one year, no significant differences were found in the mean number of febrile days (4.5 [1.5-7.4] days vs. 6.6 [2.6-10.5] days). The subgroup analysis showed that the effect of treatment on the number of febrile days was more prominent in the K15 group than in the placebo group, among children with older siblings. The 16S rRNA gene sequencing of fecal samples illustrated that the genus Faecalimonas was enriched in the K15 group, potentially promoting butyrate production by butyrate-producing bacteria. No adverse events were found to be associated with K15 intake. There were no clear data to show the effectiveness of K15 in preventing fever and RTIs in preterm babies during infancy. A larger clinical trial is warranted.

A Case of Bacteremia and Meningitis in a Neonate Infected with Group B Streptococcus via Breastfeeding Who Survived without Neurological Sequelae: A Case Report.

Invasive neonatal infection with Group B Streptococcus (GBS) is a disease of concern that can lead to neurological sequelae. Guidelines for preventing mother-to-child transmission have been introduced to reduce the incidence of early-onset infection, but guidelines for controlling the late-onset form are lacking. Recently, the trans-breastfeeding route of transmission has been highlighted as an example of late-onset infection, but no consensus on how to manage such infections has been reached. In this report, we describe a case of late-onset bacteremia/meningitis in a neonate suspected to have been infected with GBS via breastfeeding. A vaginal culture test of the mother at 35 weeks' gestation was negative for GBS. Since she had symptoms of mastitis, breast milk and nipple cultures were also tested and found to be positive for the strain of GBS identified in the neonate on genetic analysis. Diagnosis of trans-mammary GBS infection is challenging because breastfeeding-related events are difficult to identify. In our case, the diagnosis was based on the mother's history of mastitis, and the patient was treated without escalation to sequelae. When a neonate develops a fever, physicians should consider GBS infection and examine the mother's medical history to facilitate accurate diagnosis, especially if the history includes mastitis. A breast milk culture should be performed if the mother has mastitis, especially in cases of infection in preterm infants and in recurrent cases.

69 Urinary tract infections in preterm infants: Review in two Canadian tertiary centers

Abstract Background Urinary tract infections (UTI) in premature infants are commonly seen in the neonatal intensive care unit (NICU). The reported prevalence of UTI in this population ranges from 1.9-12.2% due to the lack of standardized criteria for UTI among infants less than two months of age. Enterococcus and Enterobacteriaceae are well known to cause UTI and their resistance pattern has been reported to be rising in the neonatal nosocomial infections worldwide. Objectives To describe the epidemiology, microbiology, and antimicrobial treatment for UTI in premature infants based on different diagnostic criteria. Design/Methods This retrospective study (2019-2022) included infants born at &amp;lt;33 weeks of gestational age (GA) with positive urine cultures and ≥5 days of antimicrobials treatment. We collected data from two tertiary level NICUs in Canada, including demographics, microbial susceptibility patterns, urinalysis and imaging results, and antibiotic treatment. Results We identified 43 infants managed as UTI based on physicians’ discretions. The median GA at birth was 26-27 weeks, while the median onset of first UTI ranged 39-80 days, with male predominance [Table 2]. Mixed growth of organisms constituted 21-42% of cases of UTI [Table 1]. Among UTI cases with only single growth organism, we found 53.5% and 18.6% cases fulfilled UTI diagnostic criteria based on the concentration of colony forming units (CFU) of &amp;gt;104/mL or &amp;gt;107/L and &amp;gt;105/mL or &amp;gt;108/L, respectively [Table 1]. Of these cases, 67.4% of infants had urinalysis sent with the culture, and the higher the concentration of CFU, the more likely the samples showed positive nitrites on urinalysis, with 100% correlation among those with CFU &amp;gt;105/mL or &amp;gt;108/L. [Table 1] The most common pathogens were Enterococcus species, E.Coli, Klebsiella species, Citrobacter species and Enterobacter cloacae complex [Table 2]. Among gram negative bacilli (E. Coli and Klebsiella species), greater than 42-80% were resistant to 3rd generation cephalosporins (3GC). We did not identify any vancomycin-resistant Enterococcus strains. Median duration of antimicrobial treatment ranged from 8-13 days, depending on the diagnostic criteria applied. At least 10% of infants with UTI showed abnormalities on kidney ultrasound [Table 2]. Conclusion There exists a large variation in UTI prevalence according to different diagnostic criteria. Abnormal urinalysis with presence of nitrites were frequently associated with UTI of high CFU count. High resistance to 3GC among gram negative bacilli was concerning and carried an impact on the appropriate empirical treatment choice.

53 Clinical characteristics and outcomes of children hospitalized with RSV-associated acute respiratory infections

Abstract Background Respiratory syncytial virus (RSV) is one of the most common acute respiratory infections (ARI) in infants and young children. After the relaxation of COVID-19 pandemic restrictions, children’s hospitals worldwide experienced unprecedented volumes and severity in presentation of children admitted with ARIs, such as RSV. It is unknown whether the increase in volumes was also associated with changes in the typical demographic, severity and outcomes of patients with RSV infections. Objectives To describe sociodemographic characteristics, clinical presentation, management including diagnosis and disposition and clinical outcomes of children under the age of 18 years admitted to tertiary care paediatric hospital with RSV-associated ARI. Design/Methods Observational cohort of children and adolescents aged 0-18 years admitted to two large Canadian children’s hospitals between July 1, 2022 - December 31, 2022, who had microbiological evidence of RSV infection. Detailed clinical and demographic information were extracted, including admission and discharge diagnoses, diagnostic tests, viral and bacterial testing, interventions, and respiratory settings. Clinical outcomes and complications were collected, including length of hospital admission, paediatric intensive care unit (PICU) admission, need for invasive mechanical ventilation, disposition, and death. Results There were 455 patients admitted with an RSV infection, of which a third (35.0%, n=146) were transfers from other hospitals. Cases were 41.0% male and the median age was 1.22 years (interquartile range [IQR] 0.19-3.06). Nearly two-thirds of patients (62.0%, n=284) were younger than 2 years of age, 8.6% had a history of prematurity. One third (31.0%, n=142) of patients had at least one documented comorbid condition, the most common diagnosis was asthma (6.6%). In addition to RSV, 3.5% (n=16) of patients had a simultaneous bacterial pathogen identified. Most patients (73%, n=330) were only RSV positive, while 24% (n=109) had two pathogens identified. One quarter (25.9%) were admitted to the PICU. The median length of hospital stay was 3 days (IQR 2.00-5.00) and for those admitted to the PICU, nearly two thirds of patients (63.0%, n=75) were admitted for less than 4 days. 0 patients died. The most common discharge diagnosis in 61.0% of patients (n=279) was bronchiolitis. There were 56 patients (12.3%) who had an unscheduled return visit to the ED within 30 days of discharge with 23.0% (n=13) requiring readmission to the hospital. Conclusion There continues to be a substantial volume of hospitalizations secondary to RSV infection, predominantly in those &amp;lt;2 years of age, with a prominent diagnosis of bronchiolitis. A quarter of patients had notable severity requiring PICU admission.

Exposure to HIV is associated with altered composition of maternal microchimeric T cells in infants.

HIV exposed but uninfected infants (iHEU) display altered immunity and are at increased risk of infection. We previously reported that iHEU have decreased maternal microchimerism (MMc)-maternal cells transferred to the offspring in utero/during breastfeeding. We quantified MMc in T cell subpopulations in iHEU and unexposed infants (iHU) to determine whether a selective deficiency in MMc contributes to altered cellular immunity. Across all infants, MMc levels were highest in CD8+ T cells; however, the level of CD8+ T cell MMc was lower in iHEU versus iHU. In limited functional studies, we did not identify CMV-specific MMc during infant primary infection.

Environmental exposure to tobacco smoke and the onset of respiratory infections in neonatal, infant, and childhood stages: A systematic review

Environmental exposure to tobacco smoke and the onset of respiratory infections in neonatal, infant, and childhood stages: A systematic review

Epidemiology and treatment of herpes simplex virus in the neonatal intensive care unit.

Describe the epidemiology and clinical characteristics of infants in the neonatal intensive care unit (NICU) with acyclovir exposure and herpes simplex virus (HSV) infection. Our primary analysis was to evaluate the prevalence of HSV infection among infants in the NICU who received acyclovir. We compared characteristics of infants with and without HSV and used multivariable regression analyses to assess associations between infection and clinical outcomes. Of 1,057,061 infants, 17,910 (2%) received acyclovir. Of those who received acyclovir, 1090 (5%) had HSV. Infection was associated with lower gestational age and lower birth weight. Multivariable models demonstrated that infected infants had higher mortality, greater postmenstrual age at discharge, and longer length of stay. Infants in the NICU who received acyclovir and have HSV are more likely to be born at lower gestational age, have lower birth weight, and have higher morbidities and mortality.