Whitney L. Browning

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.

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.

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 childrens 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 childrens 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.

Association between Clinical Outcomes and Hospital Guidelines for Cerebrospinal Fluid Testing in Febrile Infants Aged 29-56 Days.

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 childrens 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.

Massive Ferritin Elevation in Neonatal Herpes Simplex Virus Infection: Hemophagocytic Lymphohistiocytosis or Herpes Simplex Virus Alone?

Ilinca A. Vladescu, Whitney L. Browning, and Isaac P. Thomsen Departments of Internal Medicine and Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee; Monroe Carell, Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee; Divisions of Hospital Medicine; and Pediatric Infectious Diseases, Department of Pediatrics, Monroe Carell, Jr. Children’s Hospital at Vanderbilt, Nashville, Tennessee

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 childrens hospitals between July 1, 2011 and June 30, 2016. Each sites 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.

Factors Associated with Adverse Outcomes among Febrile Young Infants with Invasive Bacterial Infections

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.

Hospitalization for Suicide Ideation or Attempt: 2008–2015

With this study, we examined trends in encounters for SI and SA in children and adolescents ages 5 to 17 years at US children’s hospitals from 2008 to 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.