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 mL (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 mL have a low probability of IBI. WHAT'S KNOWN ON THIS SUBJECT: Commonly used risk-stratification criteria for febrile infants were either developed .2 decades ago in studies that included relatively few infants with bacteremia and/or bacterial meningitis or include procalcitonin, which is not readily available in some hospitals. WHAT THIS STUDY ADDS: A newly derived score is highly sensitive for the identification of non-ill-appearing febrile infants #60 days old with invasive bacterial infection. Infants with fever by history only, normal urinalysis results, and an absolute neutrophil count ,5185 cells per mL had a low probability of infection.

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An HSV infection was uncommon in young infants evaluated for CNS infection, particularly in the second month of life. Evidence-based approaches to the evaluation for HSV in young infants are needed.

Evidence shows that both poor physical fitness and obesity are linked to low-grade inflammation and inflammatory diseases. However, their relative roles on inflammation and underlying mechanisms remain unclear. Given the inhibitory effect of catecholamines on inflammatory cytokine production, we speculated that compromised responsiveness of immune cells’ beta adrenergic receptors (β-ARs) to agonists may be associated with constitutively elevated levels of inflammatory cytokines. We examined circulating levels of inflammatory cytokines TNF, IL-1β, IL-6 and β-AR sensitivity of, 70 overweight or obese compared to 26 normal-weight, otherwise healthy individuals in order to investigate the associations among obesity, physical fitness, and low-grade inflammation and to examine the role of β-ARs in these relationships. Cardiorespiratory fitness was determined by VO2peak (ml/kg/min) via a treadmill exercise. Beta-AR sensitivity was evaluated by measuring the degree of inhibition in lipopolysaccharides-stimulated monocytic intracellular TNF production by isoproterenol. In all participants, BMI, which was initially a predictor of IL-1β and IL-6 levels independent of demographic characteristics, no longer significantly predicted them after controlling for fitness levels. Among the overweight or obese participants, greater cardiorespiratory fitness was a strong predictor of lower levels of TNF and IL-1β after controlling for the covariates. When β-AR sensitivity was controlled for, however, fitness was no longer a significant predictor of those cytokines. Monocytic β-AR sensitivity was negatively associated with inflammatory marker levels and diminished in obese individuals; however, when fitness was controlled for, the significant weight group differences in β-AR sensitivity disappeared. Our findings indicate that better cardiorespiratory fitness protects against obesity-related low-grade inflammation and β-AR desensitization. Given the significance of β-AR function in pathogenesis of various diseases, clinical implications of its role in the fitness-inflammation association among the obese are profound.

Study Objective To determine the optimal correction factor for cerebrospinal fluid (CSF) white blood cell (WBC) counts in infants with traumatic lumbar punctures (LPs). Methods We performed a secondary analysis of a retrospective cohort of infants ≤ 60–days-old with a traumatic LP [CSF red blood cell (RBC) count ≥ 10,000 cells/mm3] at 20 participating centers. CSF pleocytosis was defined as a CSF WBC count ≥ 20 cells/mm3 for infants ≤ 28 days, ≥ 10 cells/mm3 for infants 29–60 day and bacterial meningitis as growth of pathogenic bacteria from CSF culture. Using linear regression, we derived a CSF WBC correction factor and compared the uncorrected to the corrected CSF WBC count for the detection of bacterial meningitis. Results Of the eligible 20,319 LPs, 2,880 (14%) were traumatic of whom 33 (1.1%) had bacterial meningitis. The derived CSF RBCs:WBCs ratio was 877:1 [95% confidence interval (CI) 805–961:1]. Compared with the uncorrected CSF WBC count, the corrected CSF WBC count had lower sensitivity for bacterial meningitis [88% uncorrected vs. 67% corrected; difference 21%, 95% CI 10–37%] but resulted in fewer infants with CSF pleocytosis [78% uncorrected vs. 33% corrected; difference 45%, 95% CI 43–47%]. CSF WBC count correction resulted in 7 additional infants with bacterial meningitis being misclassified as not having CSF pleocytosis; only one of these infants was > 28-days-old. Conclusion Correction of the CSF WBC count substantially reduced the number of infants with CSF pleocytosis while misclassifying only one infant with bacterial meningitis 29 to 60 days of age.

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.

The AFFIRM Study enrolled 4060 predominantly elderly patients with atrial fibrillation to compare ventricular rate control with rhythm control. The patients in the AFFIRM Study were representative of patients at high risk for complications from atrial fibrillation, which indicates that the results of this large clinical trial will be relevant to patient care.

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.