Risk Of Invasive Bacterial Infections Research Articles

Leukopenia, neutropenia, and procalcitonin levels in young febrile infants with invasive bacterial infections.

Serum procalcitonin (PCT) is a highly accurate biomarker for stratifying the risk of invasive bacterial infections (IBIs) in febrile infants ≤60 days old. However, PCT is unavailable in some settings. We explored the association of leukopenia and neutropenia with IBIs in non-critically ill febrile infants ≤60 days old, with and without PCT. We conducted a secondary analysis of a prospective observational cohort consisting of 7407 non-critically ill infants ≤60 days old with temperatures ≥38°C. We focused on the risk of IBIs in patients with leukopenia (white blood cell [WBC] count <5000 cells/μL) or neutropenia (absolute neutrophil count [ANC] <1000 cells/μL), categorized to extremes of lower values, and the impact of PCT on these associations. Multiple logistic regression was used to identify independent predictors of IBIs. Final analysis included 6865 infants with complete data; 45% (3098) had PCT data available. Of the 6865, a total of 111 (1.6%) had bacteremia without bacterial meningitis, 18 (0.3%) had bacterial meningitis without bacteremia, and 19 (0.3%) had both bacteremia and bacterial meningitis. IBI was present in four of 20 (20%) infants with WBC counts ≤2500 cells/μL and four of 311 (1.3%) with ANC <1000 cells/μL. In multivariable logistic regression analysis not including PCT, a WBC count <2500 cells/μL was significantly associated with IBI (OR 13.48, 95% CI 2.92-45.35). However, no patients with leukopenia or neutropenia and PCT ≤0.5 ng/mL had IBIs. Leukopenia ≤2500 cells/μL in febrile infants ≤60 days old is associated with IBIs. However, in the presence of normal PCT levels, no patients with leukopenia had IBIs. While this suggests leukopenia ≤2500 cells/μL is a risk factor for IBIs in non-critically ill young febrile infants only when PCT is unavailable or elevated, the overall low frequency of leukopenia in this cohort warrants caution in interpretation, with future validation required.

Performance of Febrile Infant Algorithms by Duration of Fever.

To analyze the performance of commonly used blood tests in febrile infants ≤90 days of age to identify patients at low risk for invasive bacterial infection (bacterial pathogen in blood or cerebrospinal fluid) by duration of fever. We conducted a secondary analysis of a prospective single-center registry that includes all consecutive infants ≤90 days of age with fever without a source evaluated at 1 pediatric emergency department between 2008 and 2021. We defined 3 groups based on caregiver-reported hours of fever (<2, 2-12, and ≥12) and analyzed the performance of the biomarkers and Pediatric Emergency Care Applied Research Network, American Academy of Pediatrics, and Step-by-Step clinical decision rules. We included 2411 infants; 76 (3.0%) were diagnosed with an invasive bacterial infection. The median duration of fever was 4 (interquartile range, 2-12) hours, with 633 (26.3%) patients with fever of <2 hours. The area under the curve was significantly lower in patients with <2 hours for absolute neutrophil count (0.562 vs 0.609 and 0.728) and C-reactive protein (0.568 vs 0.760 and 0.812), but not for procalcitonin (0.749 vs 0.780 and 0.773). Among well-appearing infants older than 21 days and negative urine dipstick with <2 hours of fever, procalcitonin ≥0.14 ng/mL showed a better sensitivity (100% with specificity 53.8%) than that of the combination of biomarkers of Step-by-Step (50.0% and 82.2%), and of the American Academy of Pediatrics and Pediatric Emergency Care Applied Research Network rules (83.3% and 58.3%), respectively. The performance of blood biomarkers, except for procalcitonin, in febrile young infants is lower in fever of very short duration, decreasing the accuracy of the clinical decision rules.

Predictors of Invasive Bacterial Infection in Febrile Infants Aged 2 to 6 Months in the Emergency Department

Our goal was to identify predictors of invasive bacterial infection (ie, bacteremia and bacterial meningitis) in febrile infants aged 2 to 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.

Management of well-appearing febrile young infants aged ≤90 days

Abstract The evaluation and management of young infants presenting with fever remains an area of significant practice variation. While most well-appearing febrile young infants have a viral illness, identifying those at risk for invasive bacterial infections, specifically bacteremia and bacterial meningitis, is critical. This statement considers infants aged ≤90 days who present with a rectal temperature ≥38.0°C but appear well otherwise. Applying recent risk-stratification criteria to guide management and incorporating diagnostic testing with procalcitonin are advised. Management decisions for infants meeting low-risk criteria should reflect the probability of disease, consider the balance of risks and potential harm, and include parents/caregivers in shared decision-making when options exist. Optimal management may also be influenced by pragmatic considerations, such as access to diagnostic investigations, observation units, tertiary care, and follow-up. Special considerations such as temperature measurement, risk for invasive herpes simplex infection, and post-immunization fever are also discussed.

Conundrums in the Management of Febrile Infants under Three Months of Age and Future Research.

Febrile infants under three months of age pose a diagnostic challenge to clinicians. Unlike in older children, the rates of invasive bacterial infections (IBIs), such as bacteraemia or meningitis, are high. This greater risk of IBI combined with the practical challenges of assessing young infants results in a cautious approach with many febrile infants receiving parenteral antibiotics "just in case". However, there is a range of validated tailored care guidelines that support targeted investigation and management of febrile infants, with a cohort identified as lower risk suitable for fewer invasive procedures and observation without parenteral antibiotics. This manuscript outlines five common conundrums related to the safe application of tailored-care guidelines for the assessment and management of febrile infants under three months of age. It also explores future research which aims to further refine the management of febrile infants.

Contaminant Organism Growth in Febrile Infants at Low Risk for Invasive Bacterial Infection

In this multicenter, cross-sectional, secondary analysis of 4042 low-risk febrile infants, nearly 10% had a contaminated culture obtained during their evaluation (4.9% of blood cultures, 5.0% of urine cultures, and 1.8% of cerebrospinal fluid cultures). Our findings have important implications for improving sterile technique and reducing unnecessary cultures.

Prevalence of invasive bacterial infection in febrile infants ≤90 days with a COVID-19 positive test: a systematic review and meta-analysis

BackgroundFebrile infants with an infection by influenza or enterovirus are at low risk of invasive bacterial infection (IBI).ObjectiveTo determine the prevalence of IBI among febrile infants ≤90 days old with...

Race, Ethnicity, Language, and the Treatment of Low-Risk Febrile Infants

Febrile infants at low risk of invasive bacterial infections are unlikely to benefit from lumbar puncture, antibiotics, or hospitalization, yet these are commonly performed. It is not known if there are differences in management by race, ethnicity, or language. To investigate associations between race, ethnicity, and language and additional interventions (lumbar puncture, empirical antibiotics, and hospitalization) in well-appearing febrile infants at low risk of invasive bacterial infection. This was a multicenter retrospective cross-sectional analysis of infants receiving emergency department care between January 1, 2018, and December 31, 2019. Data were analyzed from December 2022 to July 2023. Pediatric emergency departments were determined through the Pediatric Emergency Medicine Collaborative Research Committee. Well-appearing febrile infants aged 29 to 60 days at low risk of invasive bacterial infection based on blood and urine testing were included. Data were available for 9847 infants, and 4042 were included following exclusions for ill appearance, medical history, and diagnosis of a focal infectious source. Infant race and ethnicity (non-Hispanic Black, Hispanic, non-Hispanic White, and other race or ethnicity) and language used for medical care (English and language other than English). The primary outcome was receipt of at least 1 of lumbar puncture, empirical antibiotics, or hospitalization. We performed bivariate and multivariable logistic regression with sum contrasts for comparisons. Individual components were assessed as secondary outcomes. Across 34 sites, 4042 infants (median [IQR] age, 45 [38-53] days; 1561 [44.4% of the 3516 without missing sex] female; 612 [15.1%] non-Hispanic Black, 1054 [26.1%] Hispanic, 1741 [43.1%] non-Hispanic White, and 352 [9.1%] other race or ethnicity; 3555 [88.0%] English and 463 [12.0%] language other than English) met inclusion criteria. The primary outcome occurred in 969 infants (24%). Race and ethnicity were not associated with the primary composite outcome. Compared to the grand mean, infants of families that use a language other than English had higher odds of the primary outcome (adjusted odds ratio [aOR]; 1.16; 95% CI, 1.01-1.33). In secondary analyses, Hispanic infants, compared to the grand mean, had lower odds of hospital admission (aOR, 0.76; 95% CI, 0.63-0.93). Compared to the grand mean, infants of families that use a language other than English had higher odds of hospital admission (aOR, 1.08; 95% CI, 1.08-1.46). Among low-risk febrile infants, language used for medical care was associated with the use of at least 1 nonindicated intervention, but race and ethnicity were not. Secondary analyses highlight the complex intersectionality of race, ethnicity, language, and health inequity. As inequitable care may be influenced by communication barriers, new guidelines that emphasize patient-centered communication may create disparities if not implemented with specific attention to equity.

Is Ophthalmia Neonatorum Associated With Invasive Bacterial Infection? A Single-Center Retrospective Study.

Ophthalmia neonatorum (ON) is a conjunctivitis occurring in neonates and can be caused by multiple bacterial pathogens. The risk of invasive bacterial infection (IBI) in neonates with ON is poorly known. Our objectives were to document the association of ON with IBI in term neonates and to investigate practice variation. This was a retrospective observational study of all neonates who presented to a single emergency department (ED) between January 2018 and December 2019. Participants were all children with a final diagnosis of ON according to the treating physician as registered in the ED computerized database. Newborns with craniofacial malformations and premature infants were excluded. The primary outcome was IBI as defined by growth of any bacterial pathogen in the blood or cerebrospinal fluid. Perinatal risk factors, ED visit details (symptoms on presentation, management, and treatment plan) as well as complications (ocular morbidity, death, and unscheduled return visits) were collected. Data were analyzed using descriptive statistics. Fifty-two term neonates were included. There were no cases of IBI associated with ON (0%; 95% confidence interval [CI], 0%-6.9%). Six ocular bacterial infections were identified, one of which was Chlamydia trachomatis. Although there were no IBIs, ocular complications, deaths, or unscheduled return visits to the ED, there was a wide variation in physician's management of ON. Physicians ordered investigations in 49% (95% CI, 34%-62%) of neonates, prescribed antibiotics to 87% (95% CI, 74%-94%), and involved specialists in 39% (95% CI, 27%-52%) of cases. Emergency department presentations of term neonates with ON are associated with a low risk of IBI. A better understanding of the current practice variation is needed to inform clinical guidelines for the management of neonates with ON presenting to the ED.

Invasive Bacterial Infections in Children With Sickle Cell Disease: 2014-2019.

Children with sickle cell disease (SCD) are at a high risk of invasive bacterial infections (IBI). Universal penicillin prophylaxis and vaccination, especially against Streptococcus pneumoniae, have deeply changed its epidemiology. Analysis of IBI in children with SCD in a post-13-valent pneumococcal vaccine era is limited. Twenty-eight pediatric hospitals from 5 European countries retrospectively collected IBI episodes in SCD children aged 1 month to 18 years between 2014 and 2019. IBI was defined as a positive bacterial culture or polymerase chain reaction from a normally sterile fluid: blood, cerebrospinal, joint, or pleural fluid and deep surgical specimen. We recorded 169 IBI episodes. Salmonella spp. was the main isolated bacteria (n = 44, 26%), followed by Streptococcus pneumonia (Sp; n = 31, 18%) and Staphylococcus aureus (n = 20, 12%). Salmonella prevailed in osteoarticular infections and in primary bacteremia (45% and 23% of episodes, respectively) and Sp in meningitis and acute chest syndrome (88% and 50%, respectively). All Sp IBI occurred in children ≤10 years old, including 35% in children 5 to 10 years old. Twenty-seven (17%) children had complications of infection and 3 died: 2 because of Sp, and 1 because of Salmonella. The main risk factors for a severe IBI were a previous IBI and pneumococcal infection (17 Sp/51 cases). In a post-13-valent pneumococcal vaccine era, Salmonella was the leading cause of bacteremia in IBI in children with SCD in Europe. Sp came second, was isolated in children ≤10 years old, and was more likely to cause severe and fatal cases.

Management of febrile neutropenia in immunocompetent children and youth.

Febrile neutropenia is a common clinical presentation in children that can be associated with invasive bacterial infection (IBI). However, in otherwise healthy children and youth with fever and neutropenia, the risk for IBI is low, with most cases being caused by viral infections. Well-appearing, non-oncologic, and presumed immunocompetent children aged 6 months to 18 years experiencing a first episode of neutropenia, with no additional risk factors, typically do not require empiric antibiotics. However, a thorough assessment, including complete history and physical exam, is indicated, and a blood culture should be performed when the absolute neutrophil count is <0.5 × 109/L. Close follow-up, a repeat complete blood count, and strong anticipatory guidance are recommended.

Role of viral pathogen(s) detection in hospital-based management of 29-90-day-old infants with unexplained fever.

The risk for invasive bacterial infection (IBI) in young infants with fever increases the use of invasive and therapeutic interventions, such as lumbar puncture (LP) and antimicrobials which may be unnecessary. In the present study, we analyzed whether viral pathogen(s) detection using a respiratory pathogen panel (RPP) alters the use of LP and antibiotics in 29-90-day-old infants presenting with fever to a regional pediatric hospital. We collected medical history, clinical presentation, diagnostic tests and results, treatment, disposition, and length of stay (LOS) for selected patients. Data were compared between RPP positive (+) and RPP negative (-) infants. Use of LP and antibiotics were controlled for using regression analysis. P values <0.05 were considered significant. Among 172 RPP-tested infants, 45.4% had a virus(es). LP and antibiotics were used in 14.2% and 19.5% of infants in RPP(+) and in 17.0% and 28.7% in RPP(-) groups (P=0.60, 0.16), respectively. Nearly half of the infants in both groups were admitted and had comparable LOS. Hospitalization and at least one abnormal laboratory result were associated with a 2-3 times higher chance of LP and antibiotic utilization, irrespective to age and temperature level. No studied infant had been diagnosed with IBI, and 14.5% of infants in the RPP(-) group had bacteriuria. Detection of viral pathogen(s) did not significantly reduce the use of LP or antimicrobials in young infants with unexplained fever.

Invasive bacterial infection in children with fever and petechial rash in the emergency department: a national prospective observational study

ObjectiveTo determine the incidence and clinical predictors of invasive bacterial infection (IBI) in well-appearing children who present to the emergency department (ED) with fever and petechiae.DesignA prospective, observational, multicentre study...

A simple clinical decision rule may help to ruleout severe bacterial infection and spare antibiotics in febrile young children.

To assess the performance of a new clinical decision rule (CDR) to identify patients at a low risk of invasive bacterial infection (IBI) among febrile children and its theoretical impact on antibiotic use. Prospective study including consecutive children <5 years of age who presented in one French paediatric emergency department with fever without source between January and December 2016. With the collected data, we constructed a CDR based on a sequential approach based on age, clinical toxic signs, urinalysis and procalcitonin level. We evaluated its diagnostic performances to identify IBI and its potential impact on antibiotic use. Among the 1061 children (IBI 11/1061, 1.0%), 693 (65.3%) were classified at low or intermediate risk of IBI, with an IBI prevalence of 0%. The sensitivity and specificity of the CDR to predict IBI were 100% and 73.9%. Negative and positive predictive value were 100% and 3.9%, respectively. Using this new CDR, the current antibiotics exposure would theoretically be reduced from 33.6% to 24.1%. The promising interest of this clinical decision rule, using simple and accessible biological and clinical tools, needs to be confirm with an external validation study, which will allow its use in clinical practice.

Severe anaemia, iron deficiency, and susceptibility to invasive bacterial infections.

Severe anaemia and invasive bacterial infections remain important causes of hospitalization and death among young African children. The emergence and spread of antimicrobial resistance demand better understanding of bacteraemia risk factors to inform prevention strategies. Epidemiological studies have reported an association between severe anaemia and bacteraemia. In this review, we explore evidence that severe anaemia is associated with increased risk of invasive bacterial infections in young children. We describe mechanisms of iron dysregulation in severe anaemia that might contribute to increased risk and pathogenesis of invasive bacteria, recent advances in knowledge of how iron deficiency and severe anaemia impair immune responses to bacterial infections and vaccines, and the gaps in our understanding of mechanisms underlying severe anaemia, iron deficiency, and the risk of invasive bacterial infections.

67 Is Ophthalmia Neonatorum associated with Invasive Bacterial Infection? A single centre retrospective study

Abstract Background The immature immune system of neonates puts them at an increased risk of invasive bacterial infections (IBI). Ocular complications due to ophthalmia neonatorum (ON) are well described, unlike the association with IBI for which only case reports of ON with bacteremia and meningitis are documented. The risk of IBI in neonates with ophthalmia neonatorum (ON) is poorly known and part of the issue is the lack of clinical data. Objectives Our objective was to document the association of ON with IBI. Design/Methods This is a retrospective observational chart review of all afebrile neonates who presented to a single emergency department (ED) between January 2018 and December 2019 and were diagnosed with ON. Newborns with craniofacial malformations and premature infants were excluded. The primary outcome was IBI as defined by growth of any bacterial pathogen in the blood or cerebrospinal fluid. Perinatal risk factors, ED visit details (symptoms on presentation, management and treatment plan) as well as complications (ocular morbidity, death and unscheduled return visits to the ED) were collected. Data were analyzed using descriptive statistics. Results Fifty-two neonates were included in this retrospective review. There were no case of IBI associated with ON (0%, 95%CI 0-6.9%). Six ocular bacterial infections were identified, one of which was C trachomatis. Although there was no IBI, ocular complications, death or unscheduled return visits to the ED, there was a wide variation in physician management of ON. Physicians performed at least para-clinical investigation in 49% (95%CI: 34-62%) of neonates, prescribed antibiotics to 87% (95% CI: 74-94%) and involved specialists in 39% (95%CI: 27-52%) of cases. Most neonates were discharged home (92%; 95%CI: 81-98%) and three neonates (6%; 95%CI: 1-16%) were admitted to the hospital following their ED visit. Conclusion ED presentations of afebrile neonates with ON are associated with a low risk of IBI. A better understanding of the current practice variation is needed to inform clinical guidelines for the management of term neonates with ON presenting to the ED.

The risk of serious bacterial infections among young ex-premature infants with fever.

Background and ObjectivesTo determine the rate of serious-bacterial-infections (SBI) in young ex-premature infants with fever, and to develop a risk-stratification algorithm for these patients.MethodsA retrospective cohort study including all infants who presented to the pediatric emergency department (ED) of a tertiary-care university-hospital between 2010 and 2020 with fever (≥38°C), were born prematurely (<37-weeks), had post-conception age of <52-weeks, and had available blood, urine, or CSF cultures. The rates of SBI by age-of-birth and age-at-visit were calculated and compared to a cohort of matched full-term controls.ResultsThe study included a total of 290 ex-premature cases and 290 full-term controls. There were 11 cases (3.8%) with an invasive bacterial infection (IBI) of either bacteremia, meningitis or both and only six controls (2.1%) with IBI (p = 0.32). Over 28-days chronologic-age, there were 10 (3.6%) IBIs among cases and no IBIs among the controls (p = 0.02). There were eight (3%) cases and three (1%) controls with IBI who were well-appearing on physical examination (p = 0.19). All eight well-appearing ex-premature infants were under 60-days adjusted-age, seven of whom (88%) were also under 28-days adjusted-age. There were 28 (10.6%) cases and 34 (12%) controls with urinary tract infection (UTI) (p = 0.5). Among cases under 60-days adjusted-age, urinalysis was not reliable to exclude UTI (50% negative).ConclusionsWell-appearing ex-preterm infants have a significant risk for IBI until the adjusted age of 28-days and for UTI until the adjusted age of 60-days. Further studies are needed to evaluate the approach to fever in this unique population.

Effect of Prearrival Orders on Time to Antibiotics for Immunocompromised Oncology Patients Presenting to the Emergency Department With Fever.

Pediatric cancer patients with fever are at risk for invasive bacterial infection. The administration of antibiotics to these patients within the first hour of evaluation is viewed as a quality of care metric with potential to improve outcome. We sought to evaluate the impact of prearrival patient orders on the timeliness of antibiotic administration for this patient population presenting to the emergency department (ED) because of fever. A single-site pediatric ED intervention study was performed. Four hundred thirty-nine consecutively referred febrile immunocompromised pediatric oncology patients were included in the study. The intervention used structured monthly messages sent to oncology and emergency medicine providers highlighting specific roles in prehospital communication and in ED-based care emphasizing the use of standardized, prearrival order (PAO) sets. Primary outcome measures were time to antibiotic administration (TTA) and the proportions of patients receiving PAO placement and antibiotics within 60 minutes of ED arrival. Results were analyzed for the preintervention (September 2016-July 2017), intervention (August 2017-February 2018), and postintervention (March-December 2018) periods. Improvements occurred across the study periods in the proportion of patients with PAO placement (preintervention, 68%; intervention, 82%; postintervention, 87%; P = 0.001) as well as in the percentages of patients receiving antibiotics in less than 60 minutes (preintervention, 73%; intervention, 84%; postintervention, 85%; P = 0.02). Median TTA decreased from 48 to 40 minutes ( P = 0.018). Linear regression with TTA as a dependent variable revealed that PAO placement predicted a shorter TTA, decreasing by more than 15 minutes ( B = -15.90; [95% confidence interval, -20.03--11.78]; P < 0.001). Standardizing elements of prehospital communication and ED-based care using PAO sets resulted in significant improvements in time to antibiotics and in the proportion of febrile immunocompromised oncology patients receiving antibiotics within 60 minutes of ED arrival.

Derivation of a clinical-based model to detect invasive bacterial infections in febrile infants.

Febrile infants are at risk for invasive bacterial infections (IBIs) (i.e., bacteremia and bacterial meningitis), which, when undiagnosed, may have devastating consequences. Current IBI predictive models rely on serum biomarkers, which may not provide timely results and may be difficult to obtain in low-resource settings. The aim of this study was to derive a clinical-based IBI predictive model for febrile infants. This is a cross-sectional study of infants brought to two pediatric emergency departments from January 2011 to December 2018. Inclusion criteria were age 0-90 days, temperature ≥38°C, and documented gestational age, fever duration, and illness duration. To detect IBIs, we used regression and ensemble machine learning models and evidence-based predictors (i.e., sex, age, chronic medical condition, gestational age, appearance, maximum temperature, fever duration, illness duration, cough status, and urinary tract inflammation). We up-weighted infants with IBIs 8-fold and used 10-fold cross-validation to avoid overfitting. We calculated the area under the receiver operating characteristic curve (AUC), prioritizing a high sensitivity to identify the optimal cut-point to estimate sensitivity and specificity. Of 2311 febrile infants, 39 had an IBI (1.7%);the median age was 54 days (interquartile range: 35-71). The AUC was 0.819 (95% confidence interval: 0.762, 0.868). The predictive model achieved a sensitivity of 0.974 (0.800, 1.00) and a specificity of 0.530 (0.484, 0.575). Findings suggest that a clinical-based model can detect IBIs in febrile infants, performing similarly to serum biomarker-based models. This model may improve health equity by enabling clinicians to estimate IBI risk in any setting. Future studies should prospectively validate findings across multiple sites and investigate performance by age.

Prevalence and Management of Invasive Bacterial Infections in Febrile Infants Ages 2 to 6 Months

Validated prediction rules identify febrile neonates at low risk for invasive bacterial infection. The optimal approach for older febrile infants, however, remains uncertain. We performed a retrospective cohort and nested case-control study of infants 2 to 6 months of age presenting with fever (≥38.0 °C) to 1 of 5 emergency departments. The study period was from 2011 to 2019. The primary outcome was invasive bacterial infection, defined by the growth of pathogenic bacteria from either blood or cerebrospinal fluid culture. Secondary outcomes included obtaining bacterial cultures (blood, cerebrospinal fluid, or urine), administering antibiotics, and hospitalization. For the nested case-control study, we age-matched infants with invasive bacterial infection to 3 infants without invasive bacterial infection, sampled from the overall cohort. There were 21,150 eligible patient encounters over 9-years, and 101 infants had a documented invasive bacterial infection (0.48%; 95% confidence interval [CI], 0.39% to 0.58%). Invasive bacterial infection prevalence ranged from 0.2% to 0.6% among the 5 sites. The frequency of bacterial cultures ranged from 14.5% to 53.5% for blood, 1.6% to 12.9% for cerebrospinal fluid, and 31.8% to 63.2% for urine. Antibiotic administration varied from 19.2% to 46.7% and hospitalization from 16.6% to 28.3%. From the case-control study, the estimated invasive bacterial infection prevalence for previously healthy, not pretreated, and well-appearing febrile infants was 0.32% (95% CI, 0.24% to 0.41%). Although invasive bacterial infections were uncommon among febrile infants 2 to 6 months in the emergency department, the approach to diagnosis and management varied widely between sites. Therefore, evidence-based guidelines are needed to reduce low-value testing and treatment while avoiding missing infants with invasive bacterial infections.