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Our goal was to identify predictors of invasive bacterial infection (ie, bacteremia and bacterial meningitis) in febrile infants aged 2-6 months. In our multicenter retrospective cohort, older age and lower temperature identified infants at low risk for invasive bacterial infection who could safely avoid routine testing., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: The prevalence of urinary tract infection (UTI), bacteremia, and bacterial meningitis in febrile infants with SARS-CoV-2 is largely unknown. Knowledge of the prevalence of these bacterial infections among febrile infants with SARS-CoV-2 can inform clinical decision-making., Objective: To describe the prevalence of UTI, bacteremia, and bacterial meningitis among febrile infants aged 8 to 60 days with SARS-CoV-2 vs without SARS-CoV-2., Design, Setting, and Participants: This multicenter cross-sectional study was conducted as part of a quality improvement initiative at 106 hospitals in the US and Canada. Participants included full-term, previously healthy, well-appearing infants aged 8 to 60 days without bronchiolitis and with a temperature of at least 38 °C who underwent SARS-CoV-2 testing in the emergency department or hospital between November 1, 2020, and October 31, 2022. Statistical analysis was performed from September 2022 to March 2023., Exposures: SARS-CoV-2 positivity and, for SARS-CoV-2-positive infants, the presence of normal vs abnormal inflammatory marker (IM) levels., Main Outcomes and Measures: Outcomes were ascertained by medical record review and included the prevalence of UTI, bacteremia without meningitis, and bacterial meningitis. The proportion of infants who were SARS-CoV-2 positive vs negative was calculated for each infection type, and stratified by age group and normal vs abnormal IMs., Results: Among 14 402 febrile infants with SARS-CoV-2 testing, 8413 (58.4%) were aged 29 to 60 days; 8143 (56.5%) were male; and 3753 (26.1%) tested positive. Compared with infants who tested negative, a lower proportion of infants who tested positive for SARS-CoV-2 had UTI (0.8% [95% CI, 0.5%-1.1%]) vs 7.6% [95% CI, 7.1%-8.1%]), bacteremia without meningitis (0.2% [95% CI, 0.1%-0.3%] vs 2.1% [95% CI, 1.8%-2.4%]), and bacterial meningitis (<0.1% [95% CI, 0%-0.2%] vs 0.5% [95% CI, 0.4%-0.6%]). Among infants aged 29 to 60 days who tested positive for SARS-CoV-2, 0.4% (95% CI, 0.2%-0.7%) had UTI, less than 0.1% (95% CI, 0%-0.2%) had bacteremia, and less than 0.1% (95% CI, 0%-0.1%) had meningitis. Among SARS-CoV-2-positive infants, a lower proportion of those with normal IMs had bacteremia and/or bacterial meningitis compared with those with abnormal IMs (<0.1% [0%-0.2%] vs 1.8% [0.6%-3.1%])., Conclusions and Relevance: The prevalence of UTI, bacteremia, and bacterial meningitis was lower for febrile infants who tested positive for SARS-CoV-2, particularly infants aged 29 to 60 days and those with normal IMs. These findings may help inform management of certain febrile infants who test positive for SARS-CoV-2.

Objectives: Our objective was to describe the prevalence of urinary tract infection (UTI) and invasive bacterial infection (IBI) in febrile infants during the coronavirus disease 2019 pandemic., Methods: We conducted a multicenter cross-sectional study that included 97 hospitals in the United States and Canada. We included full-term, well-appearing infants 8 to 60 days old with a temperature of ≥38°C and an emergency department visit or hospitalization at a participating site between November 1, 2020 and March 31, 2022. We used logistic regression to determine trends in the odds of an infant having UTI and IBI by study month and to determine the association of COVID-19 prevalence with the odds of an infant having UTI and IBI., Results: We included 9112 infants; 603 (6.6%) had UTI, 163 (1.8%) had bacteremia without meningitis, and 43 (0.5%) had bacterial meningitis. UTI prevalence decreased from 11.2% in November 2020 to 3.0% in January 2022. IBI prevalence was highest in February 2021 (6.1%) and decreased to 0.4% in January 2022. There was a significant downward monthly trend for odds of UTI (odds ratio [OR] 0.93; 95% confidence interval [CI]: 0.91-0.94) and IBI (OR 0.90; 95% CI: 0.87-0.93). For every 5% increase in COVID-19 prevalence in the month of presentation, the odds of an infant having UTI (OR 0.97; 95% CI: 0.96-0.98) or bacteremia without meningitis decreased (OR 0.94; 95% CI: 0.88-0.99)., Conclusions: The prevalence of UTI and IBI in eligible febrile infants decreased to previously published, prepandemic levels by early 2022. Higher monthly COVID-19 prevalence was associated with lower odds of UTI and bacteremia., (Copyright © 2022 by the American Academy of Pediatrics.)

Objective: We aimed to evaluate the association of height of fever with invasive bacterial infection (IBI) among febrile infants <=60 days of age., Methods: In a secondary analysis of a multicentre case-control study of non-ill-appearing febrile infants <=60 days of age, we compared the maximum temperature (at home or in the emergency department) for infants with and without IBI. We then computed interval likelihood ratios (iLRs) for the diagnosis of IBI at each half-degree Celsius interval., Results: The median temperature was higher for infants with IBI (38.8°C; IQR 38.4-39.2) compared with those without IBI (38.4°C; IQR 38.2-38.9) (p<0.001). Temperatures 39°C-39.4°C and 39.5°C-39.9°C were associated with a higher likelihood of IBI (iLR 2.49 and 3.40, respectively), although 30.4% of febrile infants with IBI had maximum temperatures <38.5°C., Conclusions: Although IBI is more likely with higher temperatures, height of fever alone should not be used for risk stratification of febrile infants., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine the prevalence of invasive bacterial infections (IBIs) and adverse events in afebrile infants with acute otitis media (AOM)., Methods: We conducted a 33-site cross-sectional study of afebrile infants ≤90 days of age with AOM seen in emergency departments from 2007 to 2017. Eligible infants were identified using emergency department diagnosis codes and confirmed by chart review. IBIs (bacteremia and meningitis) were determined by the growth of pathogenic bacteria in blood or cerebrospinal fluid (CSF) culture. Adverse events were defined as substantial complications resulting from or potentially associated with AOM. We used generalized linear mixed-effects models to identify factors associated with IBI diagnostic testing, controlling for site-level clustering effect., Results: Of 5270 infants screened, 1637 met study criteria. None of the 278 (0%; 95% confidence interval [CI]: 0%-1.4%) infants with blood cultures had bacteremia; 0 of 102 (0%; 95% CI: 0%-3.6%) with CSF cultures had bacterial meningitis; 2 of 645 (0.3%; 95% CI: 0.1%-1.1%) infants with 30-day follow-up had adverse events, including lymphadenitis (1) and culture-negative sepsis (1). Diagnostic testing for IBI varied across sites and by age; overall, 278 (17.0%) had blood cultures, and 102 (6.2%) had CSF cultures obtained. Compared with infants 0 to 28 days old, older infants were less likely to have blood cultures ( P < .001) or CSF cultures ( P < .001) obtained., Conclusion: Afebrile infants with clinician-diagnosed AOM have a low prevalence of IBIs and adverse events; therefore, outpatient management without diagnostic testing may be reasonable., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: To describe the characteristics and outcomes of afebrile infants ≤60 days old with invasive bacterial infection (IBI)., Methods: We conducted a secondary analysis of a cross-sectional study of infants ≤60 days old with IBI presenting to the emergency departments (EDs) of 11 children's hospitals from 2011 to 2016. We classified infants as afebrile if there was absence of a temperature ≥38°C at home, at the referring clinic, or in the ED. Bacteremia and bacterial meningitis were defined as pathogenic bacterial growth from a blood and/or cerebrospinal fluid culture., Results: Of 440 infants with IBI, 78 (18%) were afebrile. Among afebrile infants, 62 (79%) had bacteremia without meningitis and 16 (20%) had bacterial meningitis (10 with concomitant bacteremia). Five infants (6%) died, all with bacteremia. The most common pathogens were Streptococcus agalactiae (35%), Escherichia coli (16%), and Staphylococcus aureus (16%). Sixty infants (77%) had an abnormal triage vital sign (temperature <36°C, heart rate ≥181 beats per minute, or respiratory rate ≥66 breaths per minute) or a physical examination abnormality (ill appearance, full or depressed fontanelle, increased work of breathing, or signs of focal infection). Forty-three infants (55%) had ≥1 of the following laboratory abnormalities: white blood cell count <5000 or >15 000 cells per μL, absolute band count >1500 cells per μl, or positive urinalysis. Presence of an abnormal vital sign, examination finding, or laboratory test result had a sensitivity of 91% (95% confidence interval 82%-96%) for IBI., Conclusions: Most afebrile young infants with an IBI had vital sign, examination, or laboratory abnormalities. Future studies should evaluate the predictive ability of these criteria in afebrile infants undergoing evaluation for IBI., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objectives: We aimed to describe the clinical and laboratory characteristics of febrile infants ≤60 days old with positive urinalysis results and invasive bacterial infections (IBI)., Methods: We performed a planned secondary analysis of a retrospective cohort study of febrile infants ≤60 days old with IBI who presented to 11 emergency departments from July 1, 2011, to June 30, 2016. For this subanalysis, we included infants with IBI and positive urinalysis results. We analyzed the sensitivity of high-risk past medical history (PMH) (prematurity, chronic medical condition, or recent antimicrobial receipt), ill appearance, and/or abnormal white blood cell (WBC) count (<5000 or >15 000 cells/μL) for identification of IBI., Results: Of 148 febrile infants with positive urinalysis results and IBI, 134 (90.5%) had bacteremia without meningitis and 14 (9.5%) had bacterial meningitis (11 with concomitant bacteremia). Thirty-five infants (23.6%) with positive urinalysis results and IBI did not have urinary tract infections. The presence of high-risk PMH, ill appearance, and/or abnormal WBC count had a sensitivity of 53.4% (95% confidence interval: 45.0-61.6) for identification of IBI. Of the 14 infants with positive urinalysis results and concomitant bacterial meningitis, 7 were 29 to 60 days old. Six of these 7 infants were ill-appearing or had an abnormal WBC count. The other infant had bacteremia with cerebrospinal fluid pleocytosis after antimicrobial pretreatment and was treated for meningitis., Conclusions: The sensitivity of high-risk PMH, ill appearance, and/or abnormal WBC count is suboptimal for identifying febrile infants with positive urinalysis results at low risk for IBI. Most infants with positive urinalysis results and bacterial meningitis are ≤28 days old, ill-appearing, or have an abnormal WBC count., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2020 by the American Academy of Pediatrics.)

In 4292 infants aged ≤60 days with cerebrospinal fluid (CSF) pleocytosis, the bacterial meningitis score had excellent sensitivity (121 of 121 [100.0%] [95% confidence interval, 96.5%-100.0%]) but low specificity (66 of 4171 [1.6%] [95% confidence interval, 1.3%-2.0%]) and therefore should not be applied clinically to infants in this age group., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: We aimed to describe the cerebrospinal fluid (CSF) profiles of infants ≤60 days old with bacterial meningitis and the characteristics of infants with bacterial meningitis who did not have CSF abnormalities., Methods: We included infants ≤60 days old with culture-positive bacterial meningitis who were evaluated in the emergency departments of 11 children's hospitals between July 1, 2011, and June 30, 2016. From medical records, we abstracted clinical and laboratory data. For infants with traumatic lumbar punctures (CSF red blood cell count of ≥10 000 cells per mm 3 ), we used a red blood cell count/white blood cell (WBC) count correction factor of 1000:1 to determine the corrected CSF WBC count. We calculated the sensitivity for bacterial meningitis of a CSF Gram-stain and corrected CSF pleocytosis (≥16 WBCs per mm 3 for infants ≤28 days old and ≥10 WBCs per mm 3 for infants 29-60 days old)., Results: Among 66 infants with bacterial meningitis, the sensitivity of a CSF Gram-stain was 71.9% (95% confidence interval [CI]: 59.2-82.4), and the sensitivity of corrected CSF pleocytosis was 80.3% (95% CI: 68.7-89.1). The sensitivity of combining positive Gram-stain results with corrected CSF pleocytosis was 86.4% (95% CI: 75.7-93.6). Of 9 infants with meningitis who had a negative Gram-stain result and no corrected CSF pleocytosis, 8 (88.9%) had either an abnormal peripheral WBC count (>15 000 or <5000 cells per μL) or bandemia >10%., Conclusions: Most infants ≤60 days old with bacterial meningitis have CSF pleocytosis or a positive Gram-stain result. Infants with no CSF pleocytosis and a negative Gram-stain result are unlikely to have bacterial meningitis in the absence of other laboratory abnormalities., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Objectives: To derive and internally validate a prediction model for the identification of febrile infants ≤60 days old at low probability of invasive bacterial infection (IBI)., Methods: We conducted a case-control study of febrile infants ≤60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated., Results: We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79-0.86]) and incorporated into an IBI score: age <21 days (1 point), highest temperature recorded in the emergency department 38.0-38.4°C (2 points) or ≥38.5°C (4 points), absolute neutrophil count ≥5185 cells per μL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score ≥2 were 98.8% (95% CI: 95.7%-99.9%) and 31.3% (95% CI: 26.3%-36.6%), respectively. All 26 infants with meningitis had scores ≥2., Conclusions: Infants ≤60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count <5185 cells per μL have a low probability of IBI., Competing Interests: POTENTIAL CONFLICT OF INTEREST: Drs Shapiro and Neuman have served as expert witnesses in malpractice cases involving the evaluation of infants with infections; the other authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Objective: To determine factors associated with adverse outcomes among febrile young infants with invasive bacterial infections (IBIs) (ie, bacteremia and/or bacterial meningitis)., Study Design: Multicenter, retrospective cohort study (July 2011-June 2016) of febrile infants ≤60 days of age with pathogenic bacterial growth in blood and/or cerebrospinal fluid. Subjects were identified by query of local microbiology laboratory and/or electronic medical record systems, and clinical data were extracted by medical record review. Mixed-effect logistic regression was employed to determine clinical factors associated with 30-day adverse outcomes, which were defined as death, neurologic sequelae, mechanical ventilation, or vasoactive medication receipt., Results: Three hundred fifty infants met inclusion criteria; 279 (79.7%) with bacteremia without meningitis and 71 (20.3%) with bacterial meningitis. Forty-two (12.0%) infants had a 30-day adverse outcome: 29 of 71 (40.8%) with bacterial meningitis vs 13 of 279 (4.7%) with bacteremia without meningitis (36.2% difference, 95% CI 25.1%-48.0%; P < .001). On adjusted analysis, bacterial meningitis (aOR 16.3, 95% CI 6.5-41.0; P < .001), prematurity (aOR 7.1, 95% CI 2.6-19.7; P < .001), and ill appearance (aOR 3.8, 95% CI 1.6-9.1; P = .002) were associated with adverse outcomes. Among infants who were born at term, not ill appearing, and had bacteremia without meningitis, only 2 of 184 (1.1%) had adverse outcomes, and there were no deaths., Conclusions: Among febrile infants ≤60 days old with IBI, prematurity, ill appearance, and bacterial meningitis (vs bacteremia without meningitis) were associated with adverse outcomes. These factors can inform clinical decision-making for febrile young infants with IBI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: The Rochester criteria were developed to identify febrile infants aged 60 days or younger at low-risk of bacterial infection and do not include cerebrospinal fluid (CSF) testing. Prior studies have not specifically assessed criteria performance for bacteremia and bacterial meningitis (invasive bacterial infection). Our objective was to determine the sensitivity of the Rochester criteria for detection of invasive bacterial infection., Methods: Retrospective cohort study of febrile infants aged 60 days or younger with invasive bacterial infections evaluated at 8 pediatric emergency departments from July 1, 2012, to June 30, 2014. Potential cases were identified from the Pediatric Health Information System using International Classification of Diseases, Ninth Revision diagnosis codes for bacteremia, meningitis, urinary tract infection, and fever. Medical record review was then performed to confirm presence of an invasive bacterial infection and to evaluate the Rochester criteria: medical history, symptoms or ill appearance, results of urinalysis, complete blood count, CSF testing (if obtained), and blood, urine, and CSF culture. An invasive bacterial infection was defined as growth of pathogenic bacteria from blood or CSF culture., Results: Among 82 febrile infants aged 60 days or younger with invasive bacterial infection, the sensitivity of the Rochester criteria were 92.7% (95% confidence interval [CI], 84.9%-96.6%) overall, 91.7% (95% CI, 80.5%-96.7%) for neonates 28 days or younger, and 94.1% (95% CI, 80.9%-98.4%) for infants aged 29 to 60 days old. Six infants with bacteremia, including 1 neonate with bacterial meningitis, met low-risk criteria., Conclusions: The Rochester criteria identified 92% of infants aged 60 days or younger with invasive bacterial infection. However, 1 neonate 28 days or younger with meningitis was classified as low-risk.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Objectives: We sought to determine the time to pathogen detection in blood and cerebrospinal fluid (CSF) for infants ≤60 days old with bacteremia and/or bacterial meningitis and to explore whether time to pathogen detection differed for non-ill-appearing and ill-appearing infants., Methods: We included infants ≤60 days old with bacteremia and/or bacterial meningitis evaluated in the emergency departments of 10 children's hospitals between July 1, 2011, and June 30, 2016. The microbiology laboratories at each site were queried to identify infants in whom a bacterial pathogen was isolated from blood and/or CSF. Medical records were then reviewed to confirm the presence of a pathogen and to extract demographic characteristics, clinical appearance, and the time to pathogen detection., Results: Among 360 infants with bacteremia, 316 (87.8%) pathogens were detected within 24 hours and 343 (95.3%) within 36 hours. A lower proportion of non-ill-appearing infants with bacteremia had a pathogen detected on blood culture within 24 hours compared with ill-appearing infants (85.0% vs 92.9%, respectively; P = .03). Among 62 infants with bacterial meningitis, 55 (88.7%) pathogens were detected within 24 hours and 59 (95.2%) were detected within 36 hours, with no difference based on ill appearance., Conclusions: Among infants ≤60 days old with bacteremia and/or bacterial meningitis, pathogens were commonly identified from blood or CSF within 24 and 36 hours. However, clinicians must weigh the potential for missed bacteremia in non-ill-appearing infants discharged within 24 hours against the overall low prevalence of infection., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

In our multicenter cohort of infants ≤60 days of age, we identified 2646 infants with a traumatic lumbar puncture, of which 31 (1.2%) had bacterial meningitis. For every 1000 cerebrospinal fluid red blood cells/mm, cerebrospinal (cerebrospinal fluid) protein increased 1.1 mg/dL (95% confidence interval: 1.0-1.2 mg/dL).

To determine age-stratified prevalence of concomitant bacterial meningitis in infants ≤60 days with a urinary tract infection, we performed a 23-center, retrospective study of 1737 infants with urinary tract infection. Concomitant bacterial meningitis was rare, but more common in infants 0-28 days of age [0.9%; 95% confidence interval (CI): 0.4%-1.9%) compared with infants 29-60 days of age (0.2%; 95% CI: 0%-0.8%).

Objective: To describe the association between clinical outcomes and clinical practice guidelines (CPGs) recommending universal cerebrospinal fluid (CSF) testing in the emergency department for febrile infants aged 29-56 days., Study Design: Using 2007-2013 administrative data from 32 US children's hospitals, we performed a difference-in-differences analysis comparing 7 hospitals with CPGs recommending universal CSF testing for older febrile infants aged 29-56 days (CPG group) with 25 hospitals without such CPGs (control group). We compared differences in clinical outcomes between older febrile infants with the corresponding differences among younger febrile infants aged 7-28 days. The primary outcome was the occurrence of an adverse event, defined as a delayed diagnosis of bacterial meningitis, mechanical ventilation, placement of a central venous catheter, extracorporeal membrane oxygenation, or in-hospital mortality. Analyses were adjusted for race/ethnicity, sex, median annual household income by zip code, primary insurance source, discharge season, and discharge year., Results: The proportion of older febrile infants undergoing CSF testing was higher (P < .001) in the CPG group (64.8%) than the control group (47.8%). CPGs recommending universal CSF testing for older febrile infants were not associated with significant differences in adverse events (difference-in-differences: +0.31 percentage points, 95% CI -0.18 to 0.85; P = .22)., Conclusions: Hospital CPGs recommending universal CSF testing for febrile infants aged 29-56 days were not associated with significant differences in clinical outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)