Safely Doing Less for Febrile Infants: Reviewing Management in the Setting of the 2021 American Academy of Pediatrics Clinical Practice Guideline.

For more than 4 decades, pediatricians have sought the best practices for effectively managing well-appearing young febrile infants. In 2021, the American Academy of Pediatrics released a clinical practice guideline for the management of well-appearing febrile infants aged 8 to 60 days. The guideline incorporates advancements in testing, such as biomarkers and diagnostic testing in the setting of changing epidemiology, to help risk stratify infants in the newly formed group age 22 to 28 days as well as the group age 29 to 60 days. The new guideline uses inflammatory markers (procalcitonin, C-reactive protein, absolute neutrophil count, and a temperature >38.4°C) to identify infants at low risk for invasive bacterial infection who can potentially avoid the invasive procedures of lumbar puncture, hospitalization, and broad-spectrum antimicrobials. Because of continued ambiguity, incorporating shared decision-making with families in the care of these infants will be important, as will ongoing clinical research to better inform future practice. [Pediatr Ann. 2024;53(6):e202-e207.].

Association of Race/Ethnicity and Social Determinants with Rehospitalization for Mental Health Conditions at Acute Care Children's Hospitals.

OBJECTIVE: To evaluate associations of race/ethnicity and social determinants with 90-day rehospitalization for mental health conditions to acute care nonpsychiatric children's hospitals. STUDY DESIGN: We conducted a retrospective cohort analysis of mental health hospitalizations for children aged 5-18 years from 2016 to 2018 at 32 freestanding US children's hospitals using the Children's Hospital Association's Pediatric Health Information System database to assess the association of race/ethnicity and social determinants (insurance payer, neighborhood median household income, and rurality of patient home location) with 90-day rehospitalization. Risk factors for rehospitalization were modeled using mixed-effects multivariable logistic regression. RESULTS: Among 23 556 index hospitalizations, there were 1382 mental health rehospitalizations (5.9%) within 90 days. Non-Hispanic Black children were 26% more likely to be rehospitalized than non-Hispanic White children (aOR 1.26, 95% CI 1.08-1.48). Those with government insurance were 18% more likely to be rehospitalized than those with private insurance (aOR 1.18, 95% CI 1.04-1.34). In contrast, those living in a suburban location were 22% less likely to be rehospitalized than those living in an urban location (suburban: aOR 0.78, 95% CI 0.63-0.97). CONCLUSIONS: Non-Hispanic Black children and those with public insurance were at greatest risk for 90-day rehospitalization, and risk was lower in those residing in suburban locations. Future work should focus on upstream interventions that will best attenuate social disparities to promote equity in pediatric mental healthcare.

Prevalence, Risk Factors, and Outcomes of Influenza-Associated Neurologic Complications in Children.

OBJECTIVE: To determine the frequency of neurologic complications associated with influenza in hospitalized children. STUD DESIGN: We performed a cross-sectional study of children (2 months through 17 years of age) with influenza discharged from 49 children's hospitals in the Pediatric Health Information System during the influenza seasons of 2015-2020. Neurologic complications were defined as encephalopathy, encephalitis, aseptic meningitis, febrile seizure, nonfebrile seizure, brain abscess and bacterial meningitis, Reye syndrome, and cerebral infarction. We assessed length of stay (LOS), intensive care unit (ICU) admission, ICU LOS, 30-day hospital readmissions, deaths, and hospital costs associated with these events. Patient-level risk factors associated with neurologic complications were identified using multivariable logistic regression. RESULTS: Of 29 676 children hospitalized with influenza, 2246 (7.6%) had a concurrent diagnosis of a neurologic complication; the most frequent were febrile seizures (5.0%), encephalopathy (1.7%), and nonfebrile seizures (1.2%). Hospital LOS, ICU admission, ICU LOS, deaths, and hospital costs were greater in children with neurologic complications compared with those without complications. Risk factors associated with neurologic complications included male sex (aOR 1.1, 95% CI 1.02-1.21), Asian race/ethnicity (aOR 1.7, 95% CI 1.4-2.1) (compared with non-Hispanic White), and the presence of a chronic neurologic condition (aOR 3.7, 95% CI 3.1-4.2). CONCLUSIONS: Neurologic complications are common in children hospitalized with influenza, especially among those with chronic neurologic conditions, and are associated with worse outcomes compared with children without neurologic complications. These findings emphasize the strategic importance of influenza immunization and treatment, especially in high-risk populations.

Implementing and Maintaining an Increased Frequency of Nighttime Education Sessions.

INTRODUCTION: Conferences are an essential component to resident education. Work hour requirements have led to night rotations, causing residents to miss this important educational experience. To fill this void, many institutions have created night curricula, but few have studied how to implement and sustain it. Our aim was to increase formal nighttime teaching led by upper level residents from 0 to ≥3 times weekly by December of 2018. METHODS: After a needs-assessment survey was completed by upper level residents, pediatric night education sessions were established. Upper level residents on wards were responsible for teaching and recording whether nighttime teaching occurred. Data were collected by using this form, and a run chart was used to analyze the data over time. A team of hospitalists, pediatric residency program leadership, and a second-year resident met throughout the project and used the model for improvement. RESULTS: Data were collected for 84 weeks. Introduction of the education sessions increased teaching occurrences from a baseline of 0 to a median of 1. After several plan, do, study, act cycles, most notably after implementing upper level feedback, special cause variation was achieved and median teaching occurrences increased to 3 times weekly. This was sustained for 32 weeks. CONCLUSIONS: Focused quality improvement methodologies can be used to improve new residency program education. These methods can inform other residency programs how to successfully weave a teaching expectation into their night shifts to provide more learning opportunities in the era of duty hour requirements.

Prevalence of Clinically Significant Drug-Drug Interactions Across US Children's Hospitals.

BACKGROUND: Little is known about the prescribing of medications with potential drug-drug interactions (DDIs) in the pediatric population. The objective of this study was to determine the prevalence and variation of prescribing medications with clinically significant DDIs across children's hospitals in the United States. METHODS: We performed a retrospective cohort study of patients <26 years of age who were discharged from 1 of 52 US children's hospitals between January 2016 and December 2018. Fifty-three drug pairings with clinically significant DDIs in children were evaluated. We identified patient-level risk factors associated with DDI using multivariable logistic regression. Adjusted hospital-level rates of DDI exposure were derived by using a generalized linear mixed-effects model, and DDI exposure variations were examined across individual hospitals. RESULTS: Across 52 children's hospitals, 47 414 (2.0%) hospitalizations included exposure to a DDI pairing (34.9 per 1000 patient-days) during the study period. One-quarter of pairings were considered contraindicated (risk grade X). After adjusting for hospital and clinical factors, there was wide variation in the percentage of DDI prescribing across hospitals, ranging from 1.05% to 4.92%. There was also substantial hospital-level variation of exposures to individual drug pairings. Increasing age, number of complex chronic conditions, length of stay, and surgical encounters were independently associated with an increased odds of DDI exposure. CONCLUSIONS: Patients hospitalized at US children's hospitals are frequently exposed to medications with clinically significant DDIs. Exposure risk varied substantially across hospitals. Further study is needed to determine the rate of adverse events due to DDI exposures and factors amenable for interventions promoting safer medication use.

Impact of clinical guidance and rapid molecular pathogen detection on evaluation and outcomes of febrile or hypothermic infants.

OBJECTIVE: To quantify the impact of clinical guidance and rapid respiratory and meningitis/encephalitis multiplex polymerase chain reaction (mPCR) testing on the management of infants. DESIGN: Before-and-after intervention study. SETTING: Tertiary-care children's hospital. PATIENTS: Infants ≤90 days old presenting with fever or hypothermia to the emergency department (ED). METHODS: The study spanned 3 periods: period 1, January 1, 2011, through December 31, 2014; period 2, January 1, 2015, through April 30, 2018; and period 3, May 1, 2018, through June 15, 2019. During period 1, no standardized clinical guideline had been established and no rapid pathogen testing was available. During period 2, a clinical guideline was implemented, but no rapid testing was available. During period 3, a guideline was in effect, plus mPCR testing using the BioFire FilmArray respiratory panel 2 (RP 2) and the meningitis encephalitis panel (MEP). Outcomes included antimicrobial and ancillary test utilization, length of stay (LOS), admission rate, 30-day mortality. Outcomes were compared across periods using Kruskal-Wallis and Pearson tests and interrupted time series analysis. RESULTS: Overall 5,317 patients were included: 2,514 in period 1, 2,082 in period 2, and 721 in period 3. Over the entire study period, we detected reductions in the use of chest radiographs, lumbar punctures, LOS, and median antibiotic duration. After adjusting for temporal trends, we observed that the introduction of the guideline was associated with reductions in ancillary tests and lumbar punctures. Use of mPCR testing with the febrile infant clinical guideline was associated with additional reductions in ancillary testing for all patients and a higher proportion of infants 29-60 days old being managed without antibiotics. CONCLUSIONS: Use of mPCR testing plus a guideline for young infant evaluation in the emergency department was associated with less antimicrobial and ancillary test utilization compared to the use of a guideline alone.

Costs and Reimbursements for Mental Health Hospitalizations at Children's Hospitals.

The financial impact of the rising number of pediatric mental health hospitalizations is unknown. Therefore, this study assessed costs, reimbursements, and net profits or losses for 111,705 mental health and non-mental health medical hospitalizations in children's hospitals with use of the Pediatric Health Information System and Revenue Management Program. Average financial margins were calculated as (reimbursement per day) - (cost per day), and they were lowest for mental health hospitalizations ($136/day), next lowest for suicide attempt ($518/day), and highest for other medical hospitalizations ($611/day). For 10 of 17 hospitals, margin per day for mental health hospitalizations was lower than margin per day for other medical hospitalizations. For these 10 hospitals, the total net loss for inpatient and observation status mental health hospitalizations, compared with other medical hospitalizations, was $27 million (median, $2.2 million per hospital). Financial margins were usually lower for mental health vs non-mental health medical hospitalizations.

Addressing Challenging Behavior During Hospitalizations for Children with Autism: A Pilot Applied Behavior Analysis Randomized Controlled Trial.

This study evaluated the feasibility, acceptance, and potential clinical benefit of brief applied behavior analysis (ABA)-based interventions for children and adolescents with autism spectrum disorder (ASD) displaying challenging behaviors during hospitalizations. Participants included 36 children diagnosed with ASD, 6-17 years of age, who were medically or psychiatrically hospitalized. Children in the intervention group received a brief ABA intervention and were compared to children in the evaluation and monitoring-only group. Families and staff recommended the intervention, children receiving the intervention demonstrated significantly more improvement in unblinded ratings of clinical severity, data from physicians indicated a positive effect of the intervention on levels of staffing and restraints and attending medical providers universally reported satisfaction and benefit of the intervention. Improvements in challenging behaviors were not significantly different as reported by parents, and the length of hospitalization did not differ between the groups. Ultimately, the outcomes of this pilot study suggest incorporating specialized ABA-based assessment and intervention during hospitalization may be feasible and well accepted by clinicians and families. However, future research must address potent methodological challenges related to capturing meaningful data during hospitalizations in order to answer questions of ultimate pragmatic, clinical, and system-level benefits. Trial Registration ClinicalTrials.gov Identifier NCT02339935, Registered 16 January 2015, First participant consented 23 February 2015. Autism Res 2020, 13: 1072-1078. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Inpatient hospitalizations for children with autism spectrum disorder (ASD) and severe behavior are common, challenging, and costly in terms of human experience. This study evaluated the benefit of brief applied behavior analysis-based interventions to children and adolescents with ASD displaying challenging behaviors during hospitalizations. Families and staff evaluating the procedures noted perceived potential benefits of the intervention, but this initial pilot study did not document changes in hospitalization length or blinded rating of improvement.

A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection.

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.

Application of the Rochester Criteria to Identify Febrile Infants With Bacteremia and Meningitis.

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.

Hospitalization for Suicide Ideation or Attempt: 2008-2015.

OBJECTIVES: Suicide ideation (SI) and suicide attempts (SAs) have been reported as increasing among US children over the last decade. We examined trends in emergency and inpatient encounters for SI and SA at US children's hospitals from 2008 to 2015. METHODS: We used retrospective analysis of administrative billing data from the Pediatric Health Information System database. RESULTS: There were 115 856 SI and SA encounters during the study period. Annual percentage of all visits for SI and SA almost doubled, increasing from 0.66% in 2008 to 1.82% in 2015 (average annual increase 0.16 percentage points [95% confidence intervals (CIs) 0.15 to 0.17]). Significant increases were noted in all age groups but were higher in adolescents 15 to 17 years old (average annual increase 0.27 percentage points [95% CI 0.23 to 0.30]) and adolescents 12 to 14 years old (average annual increase 0.25 percentage points [95% CI 0.21 to 0.27]). Increases were noted in girls (average annual increase 0.14 percentage points [95% CI 0.13 to 0.15]) and boys (average annual increase 0.10 percentage points [95% CI 0.09 to 0.11]), but were higher for girls. Seasonal variation was also observed, with the lowest percentage of cases occurring during the summer and the highest during spring and fall. CONCLUSIONS: Encounters for SI and SA at US children's hospitals increased steadily from 2008 to 2015 and accounted for an increasing percentage of all hospital encounters. Increases were noted across all age groups, with consistent seasonal patterns that persisted over the study period. The growing impact of pediatric mental health disorders has important implications for children's hospitals and health care delivery systems.

Epidemiology and Etiology of Invasive Bacterial Infection in Infants ≤60 Days Old Treated in Emergency Departments.

OBJECTIVES: To help guide empiric treatment of infants ≤60 days old with suspected invasive bacterial infection by describing pathogens and their antimicrobial susceptibilities. STUDY DESIGN: Cross-sectional study of infants ≤60 days old with invasive bacterial infection (bacteremia and/or bacterial meningitis) evaluated in the emergency departments of 11 children's hospitals between July 1, 2011 and June 30, 2016. Each site's microbiology laboratory database or electronic medical record system was queried to identify infants from whom a bacterial pathogen was isolated from either blood or cerebrospinal fluid. Medical records of these infants were reviewed to confirm the presence of a pathogen and to obtain demographic, clinical, and laboratory data. RESULTS: Of the 442 infants with invasive bacterial infection, 353 (79.9%) had bacteremia without meningitis, 64 (14.5%) had bacterial meningitis with bacteremia, and 25 (5.7%) had bacterial meningitis without bacteremia. The peak number of cases of invasive bacterial infection occurred in the second week of life; 364 (82.4%) infants were febrile. Group B streptococcus was the most common pathogen identified (36.7%), followed by Escherichia coli (30.8%), Staphylococcus aureus (9.7%), and Enterococcus spp (6.6%). Overall, 96.8% of pathogens were susceptible to ampicillin plus a third-generation cephalosporin, 96.0% to ampicillin plus gentamicin, and 89.2% to third-generation cephalosporins alone. CONCLUSIONS: For most infants ≤60 days old evaluated in a pediatric emergency department for suspected invasive bacterial infection, the combination of ampicillin plus either gentamicin or a third-generation cephalosporin is an appropriate empiric antimicrobial treatment regimen. Of the pathogens isolated from infants with invasive bacterial infection, 11% were resistant to third-generation cephalosporins alone.

Empiric Antibiotic Use and Susceptibility in Infants With Bacterial Infections: A Multicenter Retrospective Cohort Study.

OBJECTIVES: To assess hospital differences in empirical antibiotic use, bacterial epidemiology, and antimicrobial susceptibility for common antibiotic regimens among young infants with urinary tract infection (UTI), bacteremia, or bacterial meningitis. METHODS: We reviewed medical records from infants <90 days old presenting to 8 US children's hospitals with UTI, bacteremia, or meningitis. We used the Pediatric Health Information System database to identify cases and empirical antibiotic use and medical record review to determine infection, pathogen, and antimicrobial susceptibility patterns. We compared hospital-level differences in antimicrobial use, pathogen, infection site, and antimicrobial susceptibility. RESULTS: We identified 470 infants with bacterial infections: 362 (77%) with UTI alone and 108 (23%) with meningitis or bacteremia. Infection type did not differ across hospitals (P = .85). Empirical antibiotic use varied across hospitals (P < .01), although antimicrobial susceptibility patterns for common empirical regimens were similar. A third-generation cephalosporin would have empirically treated 90% of all ages, 89% in 7- to 28-day-olds, and 91% in 29- to 89-day-olds. The addition of ampicillin would have improved coverage in only 4 cases of bacteremia and meningitis. Ampicillin plus gentamicin would have treated 95%, 89%, and 97% in these age groups, respectively. CONCLUSIONS: Empirical antibiotic use differed across regionally diverse US children's hospitals in infants <90 days old with UTI, bacteremia, or meningitis. Antimicrobial susceptibility to common antibiotic regimens was similar across hospitals, and adding ampicillin to a third-generation cephalosporin minimally improves coverage. Our findings support incorporating empirical antibiotic recommendations into national guidelines for infants with suspected bacterial infection.

Accuracy of diagnosis codes to identify febrile young infants using administrative data.

BACKGROUND: Administrative data can be used to determine optimal management of febrile infants and aid clinical practice guideline development. OBJECTIVE: Determine the most accurate International Classification of Diseases, Ninth Revision (ICD-9) diagnosis coding strategies for identification of febrile infants. DESIGN: Retrospective cross-sectional study. SETTING: Eight emergency departments in the Pediatric Health Information System. PATIENTS: Infants aged <90 days evaluated between July 1, 2012 and June 30, 2013 were randomly selected for medical record review from 1 of 4 ICD-9 diagnosis code groups: (1) discharge diagnosis of fever, (2) admission diagnosis of fever without discharge diagnosis of fever, (3) discharge diagnosis of serious infection without diagnosis of fever, and (4) no diagnosis of fever or serious infection. EXPOSURE: The ICD-9 diagnosis code groups were compared in 4 case-identification algorithms to a reference standard of fever ≥100.4°F documented in the medical record. MEASUREMENTS: Algorithm predictive accuracy was measured using sensitivity, specificity, and negative and positive predictive values. RESULTS: Among 1790 medical records reviewed, 766 (42.8%) infants had fever. Discharge diagnosis of fever demonstrated high specificity (98.2%, 95% confidence interval [CI]: 97.8-98.6) but low sensitivity (53.2%, 95% CI: 50.0-56.4). A case-identification algorithm of admission or discharge diagnosis of fever exhibited higher sensitivity (71.1%, 95% CI: 68.2-74.0), similar specificity (97.7%, 95% CI: 97.3-98.1), and the highest positive predictive value (86.9%, 95% CI: 84.5-89.3). CONCLUSIONS: A case-identification strategy that includes admission or discharge diagnosis of fever should be considered for febrile infant studies using administrative data, though underclassification of patients is a potential limitation.

Pediatric hospitalist perceptions regarding trainees' effects on cost and quality of care.

OBJECTIVE: To determine pediatric hospitalists' perceptions about residents' effects on cost and quality of care and their own ability to provide and teach cost-effective, high-quality care. METHODS: A 15-item survey assessing hospitalist perceptions of resident impact on costs/quality and their role in teaching cost-effectiveness was developed and sent to 180 hospitalists from 113 institutions in the United States. RESULTS: Of 180 hospitalists surveyed, 127 completed surveys (71%). Overall, 76 (60%) and 91 (72%) hospitalists believed that residents increase quality and cost of care, respectively. Respondents who worked with residents all the time were more likely to state that residents increase quality (50 of 70 [71%]) compared with those who worked with residents sometimes (18 of 42 [43%]) or never (8 of 15 [53%]; P=.01). Similarly, academic hospitalists were more likely than community hospitalists to believe that residents increase quality (67 of 103 [65%] vs 9 of 24 [38%]; P=.03). Although only 28 (22%) respondents reported receiving formal cost-effectiveness training, 116 (91%) believed that they provided cost-effective care, and 103 (81%) believed that they were qualified to teach this topic. Most respondents (n=115 [91%]) believed that residents should participate in a cost-effectiveness curriculum. CONCLUSIONS: Most respondents felt trainees increase both the costs and quality of care for hospitalized children. The perception of increased quality was associated with increased resident interaction, whereas cost perceptions were similar across groups. Pediatric hospitalists report a lack of formal cost-effectivesness training, but nearly all respondents supported the incorporation of such training into graduate medical education programs.

Association of clinical practice guidelines with emergency department management of febrile infants ≤56 days of age.

BACKGROUND: Differences among febrile infant institutional clinical practice guidelines (CPGs) may contribute to practice variation and increased healthcare costs. OBJECTIVE: Determine the association between pediatric emergency department (ED) CPGs and laboratory testing, hospitalization, ceftriaxone use, and costs in febrile infants. DESIGN: Retrospective cross-sectional study in 2013. SETTING: Thirty-three hospitals in the Pediatric Health Information System. PATIENTS: Infants aged ≤56 days with a diagnosis of fever. EXPOSURES: The presence and content of ED-based febrile infant CPGs assessed by electronic survey. MEASUREMENTS: Using generalized estimating equations, we evaluated the association between CPG recommendations and rates of urine, blood, cerebrospinal fluid (CSF) testing, hospitalization, and ceftriaxone use at ED discharge in 2 age groups: ≤28 days and 29 to 56 days. We also assessed CPG impact on healthcare costs. RESULTS: We included 9377 ED visits; 21 of 33 EDs (63.6%) had a CPG. For neonates ≤28 days, CPG recommendations did not vary and were not associated with differences in testing, hospitalization, or costs. Among infants 29 to 56 days, CPG recommendations for CSF testing and ceftriaxone use varied. CSF testing occurred less often at EDs with CPGs recommending limited testing compared to hospitals without CPGs (adjusted odds ratio: 0.5, 95% confidence interval: 0.3-0.8). Ceftriaxone use at ED discharge varied significantly based on CPG recommendations. Costs were higher for admitted and discharged infants 29 to 56 days old at hospitals with CPGs. CONCLUSIONS: CPG recommendations for febrile infants 29 to 56 days old vary across institutions for CSF testing and ceftriaxone use, correlating with observed practice variation. CPGs were not associated with lower healthcare costs.