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.

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.

Facing the ongoing challenge of the febrile young infant.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2017. Other selected articles can be found online at http://ccforum.com/series/annualupdate2017 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901 .

Factors Associated With Prolonged Mental Health Admissions at US Children's Hospitals.

BACKGROUND AND OBJECTIVES: Mental health (MH) hospitalizations at medical hospitals are associated with longer length of stay (LOS) compared with non-MH hospitalizations, but patient factors and costs associated with prolonged MH hospitalizations are unknown. The objective of this paper is to assess patient clinical and demographic factors associated with prolonged MH hospitalizations and describe variation in MH LOS across US children's hospitals. METHODS: We studied children aged 5 to 20 years hospitalized with a primary MH diagnosis during 2021 and 2022 across 46 children's hospitals using the Pediatric Health Information System database. Generalized estimating equations, clustered on hospital, tested associations between patient characteristics with prolonged MH hospitalization, defined as those in the 95th percentile or above (>14 days). RESULTS: Among 42 654 primary MH hospitalizations, most were aged 14 to 18 (62.4%), female (68.5%), and non-Hispanic white (53.8%). The most common primary MH diagnoses were suicide/self-injury (37.4%), depressive disorders (16.6%), and eating disorders (10.9%). The median (interquartile range) LOS was 2 days (1-5), but 2169 (5.1%) experienced a hospitalization >14 days. In adjusted analyses, race and ethnicity, category of MH diagnosis, and increasing medical and MH complexity were associated with prolonged hospitalization. CONCLUSIONS: Our results emphasize several diagnoses and clinical descriptors for targeted interventions, such as behavioral and inpatient MH resources and discharge planning. Expanded investment in both community and inpatient MH supports have the potential to improve health equity and reduce prolonged MH hospitalizations.

Characteristics of Patients Associated With Restraint Use at a Midwest Children's Hospital.

BACKGROUND AND OBJECTIVES: Restraint use is associated with negative mental health outcomes, injury risk, and known disparities in use. Improved understanding of restraint use among hospitalized children is critical given the increased frequency of hospitalized children with complex and/or acute mental health needs. Our objective is to describe the demographic and clinical features of children associated with mechanical restraint. METHODS: In a single-center retrospective cohort study of patients hospitalized from 2017 to 2021, restraint encounters were identified from electronic health records. Odds of restraint was modeled as a function of patient demographic and clinical characteristics, as well as hospitalization characteristics using logistic regression modeling adjusted for clustering of hospitalizations within patients and for varying lengths of stay. RESULTS: Among 29 808 children (46 302 encounters), 225 patients (275 encounters) had associated restraint use. In regression modeling, odds of restraint were higher with restraint at the preceding hospitalization (adjusted odds ratio [aOR] 8.6, 95% confidence interval [CI] 4.8-15.5), diagnosis of MH conditions such as psychotic disorders (aOR 5.4, 95% CI 2.7-10.4) and disruptive disorders (aOR 4.7, 95% CI 2.8-7.8), male sex (aOR 1.9, 95% CI 1.5-2.5), and Black race (aOR relative to White patients 1.9, 95% CI 1.4-2.6). CONCLUSIONS: Our results suggest racial inequities in restraint use for hospitalized children. This finding mirrors inequities in restraint use in the emergency department and adult settings. Understanding the behavioral needs of such patients may help in reducing restraint use and improving health equity.

Payer-Related Sources of Variation in Febrile Infant Management Before and After a National Practice Standardization Initiative.

OBJECTIVES: Sources of variation within febrile infant management are incompletely described. In 2016, a national standardization quality improvement initiative, Reducing Excessive Variation in Infant Sepsis Evaluations (REVISE) was implemented. We sought to: (1) describe sociodemographic factors influencing laboratory obtainment and hospitalization among febrile infants and (2) examine the association of REVISE on any identified sources of practice variation. METHODS: We included febrile infants ≤60 days of age evaluated between December 1, 2015 and November 30, 2018 at Pediatric Health Information System-reporting hospitals. Patient demographics and hospital characteristics, including participation in REVISE, were identified. Factors associated with variation in febrile infant management were described in relation to the timing of the REVISE initiative. RESULTS: We identified 32 572 febrile infants in our study period. Pre-REVISE, payer-type was associated with variation in laboratory obtainment and hospitalization. Compared with those with private insurance, infants with self-pay (adjusted odds ratio [aOR] 0.43, 95% confidence interval [95% CI] 0.22-0.5) or government insurance (aOR 0.67, 95% CI 0.60-0.75) had lower odds of receiving laboratories, and self-pay infants had lower odds of hospitalization (aOR 0.38, 95% CI 0.28-0.51). Post-REVISE, payer-related disparities in care remained. Disparities in care were not associated with REVISE participation, as the interaction of time and payer was not statistically different between non-REVISE and REVISE centers for either laboratory obtainment (P = .09) or hospitalization (P = .67). CONCLUSIONS: Payer-related care inequalities exist for febrile infants. Patterns in disparities were similar over time for both non-REVISE and REVISE-participating hospitals. Further work is needed to better understand the role of standardization projects in reducing health disparities.

Characteristics of Afebrile Infants ≤60 Days of Age With Invasive Bacterial Infections.

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.

Height of fever and invasive bacterial infection.

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.

Variation in Care and Clinical Outcomes Among Infants Hospitalized With Hyperbilirubinemia.

OBJECTIVES: To assess hospital-level variation in laboratory testing and intravenous fluid (IVF) use and examine the association between these interventions and hospitalization outcomes among infants admitted with neonatal hyperbilirubinemia. METHODS: We performed a retrospective multicenter study of infants aged 2 to 7 days hospitalized with a primary diagnosis of hyperbilirubinemia from December 1, 2016, to June 30, 2018, using the Pediatric Health Information System. Hospital-level variation in laboratory and IVF use was evaluated after adjusting for clinical and demographic factors and associated with hospital-level outcomes by using Pearson correlation. RESULTS: We identified 4396 infants hospitalized with hyperbilirubinemia. In addition to bilirubin level, the most frequently ordered laboratories were direct antiglobulin testing (45.7%), reticulocyte count (39.7%), complete blood cell counts (43.7%), ABO blood type (33.4%), and electrolyte panels (12.9%). IVFs were given to 26.3% of children. Extensive variation in laboratory testing and IVF administration was observed across hospitals (all P < .001). Increased use of laboratory testing but not IVFs was associated with a longer length of stay (P = .007 and .162, respectively). Neither supplementary laboratory use nor IVF use was associated with either readmissions or emergency department revisits. CONCLUSIONS: Substantial variation exists among hospitals in the management of infants with hyperbilirubinemia. With our results, we suggest that additional testing outside of bilirubin measurement may unnecessarily increase resource use for infants hospitalized with hyperbilirubinemia.

Febrile Infants ≤60 Days Old With Positive Urinalysis Results and Invasive Bacterial Infections.

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.

Cerebrospinal Fluid Profiles of Infants ≤60 Days of Age With Bacterial Meningitis.

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 mm3), 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 mm3 for infants ≤28 days old and ≥10 WBCs per mm3 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.

Parenteral Antibiotic Therapy Duration in Young Infants With Bacteremic Urinary Tract Infections.

OBJECTIVES: To determine the association between parenteral antibiotic duration and outcomes in infants ≤60 days old with bacteremic urinary tract infection (UTI). METHODS: This multicenter retrospective cohort study included infants ≤60 days old who had concomitant growth of a pathogen in blood and urine cultures at 11 children's hospitals between 2011 and 2016. Short-course parenteral antibiotic duration was defined as ≤7 days, and long-course parenteral antibiotic duration was defined as >7 days. Propensity scores, calculated using patient characteristics, were used to determine the likelihood of receiving long-course parenteral antibiotics. We conducted inverse probability weighting to achieve covariate balance and applied marginal structural models to the weighted population to examine the association between parenteral antibiotic duration and outcomes (30-day UTI recurrence, 30-day all-cause reutilization, and length of stay). RESULTS: Among 115 infants with bacteremic UTI, 58 (50%) infants received short-course parenteral antibiotics. Infants who received long-course parenteral antibiotics were more likely to be ill appearing and have growth of a non-Escherichia coli organism. There was no difference in adjusted 30-day UTI recurrence between the long- and short-course groups (adjusted risk difference: 3%; 95% confidence interval: -5.8 to 12.7) or 30-day all-cause reutilization (risk difference: 3%; 95% confidence interval: -14.5 to 20.6). CONCLUSIONS: Young infants with bacteremic UTI who received ≤7 days of parenteral antibiotics did not have more frequent recurrent UTIs or hospital reutilization compared with infants who received long-course therapy. Short-course parenteral therapy with early conversion to oral antibiotics may be considered in this population.

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.

Time to Pathogen Detection for Non-ill Versus Ill-Appearing Infants ≤60 Days Old With Bacteremia and Meningitis.

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.

Risk Stratification of Febrile Infants ≤60 Days Old Without Routine Lumbar Puncture.

: media-1vid110.1542/5840460609001PEDS-VA_2018-1879Video Abstract OBJECTIVES: To evaluate the Rochester and modified Philadelphia criteria for the risk stratification of febrile infants with invasive bacterial infection (IBI) who do not appear ill without routine cerebrospinal fluid (CSF) testing. METHODS: We performed a case-control study of febrile infants ≤60 days old presenting to 1 of 9 emergency departments from 2011 to 2016. For each infant with IBI (defined as a blood [bacteremia] and/or CSF [bacterial meningitis] culture with growth of a pathogen), controls without IBI were matched by site and date of visit. Infants were excluded if they appeared ill or had a complex chronic condition or if data for any component of the Rochester or modified Philadelphia criteria were missing. RESULTS: Overall, 135 infants with IBI (118 [87.4%] with bacteremia without meningitis and 17 [12.6%] with bacterial meningitis) and 249 controls were included. The sensitivity of the modified Philadelphia criteria was higher than that of the Rochester criteria (91.9% vs 81.5%; P = .01), but the specificity was lower (34.5% vs 59.8%; P < .001). Among 67 infants >28 days old with IBI, the sensitivity of both criteria was 83.6%; none of the 11 low-risk infants had bacterial meningitis. Of 68 infants ≤28 days old with IBI, 14 (20.6%) were low risk per the Rochester criteria, and 2 had meningitis. CONCLUSIONS: The modified Philadelphia criteria had high sensitivity for IBI without routine CSF testing, and all infants >28 days old with bacterial meningitis were classified as high risk. Because some infants with bacteremia were classified as low risk, infants discharged from the emergency department without CSF testing require close follow-up.