UNASSIGNED: Febrile young infants are at risk of serious bacterial infections (SBIs), which are potentially life-threatening. This study aims to investigate the association between delayed presentation and the risk of SBIs among febrile infants.
UNASSIGNED: We performed a prospective cohort study on febrile infants ≤90 days old presenting to a Singapore paediatric emergency department (ED) between November 2017 and July 2022. We defined delayed presentation as presentation to the ED >24 hours from fever onset. We compared the proportion of SBIs in infants who had delayed presentation compared to those without, and their clinical outcomes. We also performed a multivariable logistic regression to study if delayed presentation was independently associated with the presence of SBIs.
UNASSIGNED: Among 1911 febrile infants analysed, 198 infants (10%) had delayed presentation. Febrile infants with delayed presentation were more likely to have SBIs (28.8% versus [vs] 16.3%, P<0.001). A higher proportion of infants with delayed presentation required intravenous antibiotics (64.1% vs 51.9%, P=0.001). After adjusting for age, sex and severity index score, delayed presentation was independently associated with the presence of SBI (adjusted odds ratio [AOR] 1.78, 95% confidence interval 1.26-2.52, P<0.001).
UNASSIGNED: Febrile infants with delayed presentation are at higher risk of SBI. Frontline clinicians should take this into account when assessing febrile infants.

UNASSIGNED: Respiratory viral infections are common in febrile infants ≤90 days. However, the detection of viruses other than enterovirus in the blood and cerebrospinal fluid (CSF) of young infants is not well defined. We sought to quantify the occurrence of respiratory viruses in the blood and CSF of febrile infants ≤90 days.
UNASSIGNED: We conducted a nested cohort study examining plasma and CSF samples from febrile infants 15-90 days via rtPCR. The samples were tested for respiratory viruses (respiratory syncytial virus, influenza, enterovirus, parechovirus, adenovirus, bocavirus). Clinical and laboratory data were also collected to determine the presence of serious bacterial infections (SBI).
UNASSIGNED: Twenty-four percent (30 of 126) of infants had plasma/CSF specimens positive for a respiratory virus. Enterovirus and parechovirus were the most commonly detected respiratory viruses. Viral positivity was highest in plasma samples at 25% (27 of 107) compared with CSF samples at 15% (nine of 62). SBIs (specifically urinary tract infections) were less common in infants with a sample positive for a respiratory virus compared to those without a virus detected (3% vs. 26%, p = 0.008).
UNASSIGNED: Our findings support the use of molecular diagnostics to include the identification of parechovirus in addition to enterovirus in febrile infants ≤90 days. Additionally, these data support the utilization of blood specimens to diagnose enterovirus and parechovirus infections in febrile infants ≤90 days.

Routine blood examination is an easy way to examine infectious diseases. This study is aimed to develop a model to diagnose serious bacterial infections (SBI) in ICU neonates based on routine blood parameters. This was a cross-sectional study, and data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III). SBI was defined as suffering from one of the following: pyelonephritis, bacteraemia, bacterial meningitis, sepsis, pneumonia, cellulitis, and osteomyelitis. Variables with statistical significance in the univariate logistic regression analysis and log systemic immune-inflammatory index (SII) were used to develop the model. The area under the curve (AUC) was calculated to assess the performance of the model. A total of 1,880 participants were finally included for analysis. Weight, haemoglobin, mean corpuscular volume, white blood cell, monocyte, premature delivery, and log SII were selected to develop the model. The developed model showed a good performance to diagnose SBI for ICU neonates, with an AUC of 0.812 (95% confidence interval (CI): 0.737-0.888). A nomogram was developed to make this model visualise. In conclusion, our model based on routine blood parameters performed well in the diagnosis of neonatal SBI, which may be helpful for clinicians to improve treatment recommendations.

UNASSIGNED: Febrile neutropenia (FN) creates concern in paediatrics due to the risk of serious bacterial infections (SBI). Protocols with empiric antibiotics designed for hematology and oncology are often applied in healthy children with FN despite lower rates of SBI in this population. This study quantifies rates of infections in presumed immunocompetent children hospitalized with suspected viral illnesses and FN.
UNASSIGNED: This was a retrospective chart review of healthy children admitted to the Stollery Children\'s Hospital between 2007 and 2017 with fever, absolute neutrophil counts < 0.5 × 109/L, and viral symptoms. Primary outcomes were the incidence of SBI and bacterial pneumonia.
UNASSIGNED: Of 383 encounters reviewed, 96 admissions for 82 patients met inclusion criteria. Eighty-eight encounters (91.7%) were managed with empiric antibiotics. Viruses were identified in 42% of encounters. Three blood cultures were positive for coagulase-negative Staphylococcus and one for Coryneforms, all considered contaminants. There were three urinary tract infections and two pneumonias. Eighty-three per cent of patients had normalization of neutrophil counts, with a median neutropenia duration of 3.2 months. Follow-up diagnoses included chronic benign neutropenia of childhood (N = 17) and three rheumatologic/autoimmune conditions (N = 3).
UNASSIGNED: Our results support previous findings of low rates of invasive bacterial infections in healthy children with FN. With an SBI rate of 3.1% and few patients found to have any pathologic etiology for their neutropenia, prospective studies would be valuable to evaluate the need for a practice change regarding antibiotic use in low-risk patients with suspected viral-induced neutropenia.

OBJECTIVE: To assess the efficacy, pharmacokinetics, and safety of a new, highly purified 10% IVIg (BT595, Yimmugo®) administered in children with PID.
METHODS: This was an open-label, prospective, uncontrolled, multicenter Phase III pivotal trial. Among the 67 subjects in the trial were 18 pediatric patients aged 2 to 17 years with diagnosis of PID included in this analysis. They received doses between 0.2 and 0.8 g/kg body weight for approximately 12 months at intervals of either 3 or 4 weeks. Dosage and dosing interval were based on each patient\'s pre-trial infusion schedule. The rates of acute serious bacterial infections (SBI), secondary efficacy, safety, and pharmacokinetic outcomes were evaluated.
RESULTS: No SBI occurred in the pediatric population. Two hundred sixty infusions were administered to the 18 pediatric patients. The mean (SD) IgG trough level was 8.55 (1.67) g/L at baseline and 8.84 (2.17) g/L at the follow-up visit after the last BT595 infusion. At the single infusions respectively, the average mean IgG trough levels ranged between 8.52 and 10.58 g/L. More than 85% of all infusions administered were not associated with any infusional AE (start during or within 72 h post-infusion). None of the severe or serious AEs were related to the investigational medicinal product (IMP). No premedication was used. Thirteen children reached a maximum infusion rate between > 2.0 and 8 mL/kg/h; no AE with an onset during the infusion occurred at these infusion rates.
CONCLUSIONS: BT595 is effective, convenient, well tolerated, and safe for the treatment of children with PID.
BACKGROUND: EudraCT: 2015-003652-52; NCT02810444, registered June 23, 2016.

Hypothermic infants are at risk for serious bacterial and herpes simplex virus infections, but there are no evidence-based guidelines for managing these patients. We sought to characterize variations and trends in care for these infants in the emergency department (ED).
We conducted a retrospective cross-sectional study of infants under 90 days old presenting to 32 pediatric EDs from 2009 through 2019 with an International Classification of Diseases diagnosis code for hypothermia. We characterized variation in diagnostic testing, antimicrobial treatment, and disposition of children in three age groups (≤30 days, 31-60 days, and 61-90 days old) and analyzed care trends.
Of 7828 ED encounters meeting inclusion criteria, most (81%) were ≤ 30 days of age. Infants in the 0-30 days old age group, compared to 61-90 days old age group, had a higher proportion of blood (75% vs. 68%), urine (72% vs. 64%), and cerebrospinal fluid (CSF; 35% vs. 22%) cultures obtained (p < 0.01) and greater antimicrobial use (81% vs. 68%; p < 0.01) in the ED. From 2009 to 2019, C-reactive protein (CRP), and procalcitonin usage steadily increased, from 25% to 40% and 0% to 30% respectively, while antibiotic use (83% to 77%), CSF testing (53% to 44%), and chest radiography (47% to 34%) decreased. Considerable interhospital variation was noted in testing and treatment, including CSF testing (14-70%), inflammatory markers (CRP and procalcitonin; 8-88%), and antibiotics (56-92%).
Substantial hospital-level variation exists for managing hypothermic infants in the ED. Long-term trends are notable for changing practice over time, particularly with increased use of inflammatory markers. Prospective studies are needed to risk stratify and optimize care for this population.

UNASSIGNED: This review summarises epidemiological research using electronic health records (EHR) for antimicrobial stewardship.
UNASSIGNED: EHRs enable surveillance of antibiotic utilisation and infection consultations. Prescribing for respiratory tract infections has declined in the UK following reduced consultation rates. Reductions in prescribing for skin and urinary tract infections have been less marked. Drug selection has improved and use of broad-spectrum antimicrobics reduced. Diagnoses of pneumonia, sepsis and bacterial endocarditis have increased in primary care. Analytical studies have quantified risks of serious bacterial infections following reduced antibiotic prescribing. EHRs are increasingly used in interventional studies including point-of-care trials and cluster randomised trials of quality improvement. Analytical and interventional studies indicate patient groups for whom antibiotic utilisation may be more safely reduced.
UNASSIGNED: EHRs offer opportunities for surveillance and interventions that engage practitioners in the effects of improved prescribing practices, with the potential for better outcomes with targeted study designs.

UNASSIGNED: This study analyzed the utility of the systemic immune-inflammation index (SII) in predicting serious bacterial infections (SBIs) in infants with fever without a source (FWS).
UNASSIGNED: Infants (aged 1-4 months) evaluated in the pediatric emergency department for FWS were divided into two groups: with SBI and without SBI. The efficacy of inflammatory markers in predicting SBI was compared.
UNASSIGNED: The study included 223 infants with a mean age of 76.65 ± 25.42 days; 62 (27.8%) of them were included in the SBI group, and all of them were diagnosed with a urinary tract infection (UTI). The hospitalization rate and length of hospital stay were significantly higher in UTI patients (p < 0.001 for each). The mean SII was 795.76 ± 475.85 in the SBI group and 318.24 ± 300.70 in the non-SBI group, and there was a significant difference between the groups (p < 0.001). In diagnosis of SBI, the area under the curve values were found to be 0.89 [95% confidence interval (CI): 0.85-0.94] for C-reactive protein (CRP), 0.86 (95% CI: 0.81-0.91) for absolute neutrophil count (ANC), 0.84 (95% CI: 0.78-0.89) for the SII, and 0.81 (95% CI: 0.74-0.87) for WBC. In the multivariate logistic regression analysis, high CRP and SII values were found to be predictive factors for UTI without bacteremia (p < 0.001 and p = 0.008, respectively).
UNASSIGNED: We found that high CRP and SII values could be predictive for UTI without bacteremia in infants with FWS. The SII may be preferred because it can be easily calculated using the hemogram results, is not accompanied by extra costs, and does not require further blood collection.

UNASSIGNED: Fear of missed serious bacterial infections (SBIs) results in many febrile young infants receiving antibiotics. We aimed to compare the time to antibiotics between infants with SBIs and those without.
UNASSIGNED: We recruited febrile infants ≤ 90 days old seen in the emergency department (ED) between December 2017 and April 2021. SBI was defined as (1) urinary tract infection, (2) bacteremia or (3) bacterial meningitis. We compared the total time (median with interquartile range, IQR) from ED arrival to infusion of antibiotics, divided into (i) time from triage to decision for antibiotics and (ii) time from decision for antibiotics to administration of antibiotics.
UNASSIGNED: We analyzed 81 and 266 infants with and without SBIs. Median age of those with and without SBIs were 44 (IQR 19-72) and 29 (IQR 7-56) days, respectively (p = 0.002). All infants with SBIs and 168/266 (63.2%) infants without SBIs received antibiotics. Among 249 infants who received antibiotics, the median total time from ED arrival to infusion of antibiotics was 277.0 (IQR 236.0-385.0) mins for infants with SBIs and 304.5 (IQR 238.5-404.0) mins for those without (p = 0.561). The median time to decision for antibiotics was 156.0 (IQR 115.0-255.0) mins and 144.0 (IQR 105.5-211.0) mins, respectively (p = 0.175). Following decision for antibiotics, infants with SBIs received antibiotics much faster compared to those without [107.0 (IQR 83.0-168.0) vs. 141.0 (94.0-209.5) mins, p = 0.017].
UNASSIGNED: There was no difference in total time taken to antibiotics between infants with SBIs and without SBIs. Both recognition and administration delays were observed. While all infants with SBIs were adequately treated, more than half of the infants without SBIs received unnecessary antibiotics. This highlights the challenge in managing young febrile infants at initial presentation, and demonstrates the need to examine various aspects of care to improve the overall timeliness to antibiotics.

Febrile infants ≤ 90 days old make up a significant proportion of patients seeking care in the emergency department (ED). These infants are vulnerable to serious bacterial infections (SBIs) and early identification is required to initiate timely investigations and interventions. We aimed to study if height of an infant\'s temperature on presentation to the ED is associated with SBI.
We performed a retrospective chart review on febrile infants ≤ 90 days old presenting to our ED between 31st March 2015 and 28th February 2016. We compared triage temperature of febrile infants with and without SBIs. We presented sensitivity, specificity, positive and negative predictive values (PPV and NPV) of fever thresholds at triage. A multivariable regression was performed to study the association between height of temperature and the presence of SBI, and presented the adjusted odds ratio (aOR) with corresponding 95% confidence intervals (CI).
Among 1057 febrile infants analysed, 207 (19.6%) had a SBI. Mean temperature of infants with a SBI was significantly higher than those without (mean 38.5 °C, standard deviation, SD 0.6 vs. 38.3 °C, SD 0.5, p < 0.005). For temperature ≥ 39 °C, sensitivity, specificity, PPV and NPV for SBI was 15.5% (95%CI 10.8-21.1%), 90.4% (95%CI 88.2-92.3%), 28.1% (95%CI 21.1-36.3%) and 81.4% (95%CI 80.5-82.4%) respectively. The height of fever was consistently associated with SBI after adjusting for age, gender and SIS (aOR 1.76, 95% CI 1.32-2.33, p < 0.001). However, 32 (15.5%) infants with SBIs had an initial triage temperature ≤ 38 °C.
A higher temperature at triage was associated with a higher risk of SBI among febrile infants ≤ 90 days old. However, height of temperature must be used in conjunction with other risk factors to identify SBIs in young infants.