Although neonatal herpes simplex virus (HSV) causes significant morbidity, utilization of the cerebrospinal fluid (CSF) HSV polymerase chain reaction (PCR) test remains variable. Our objective was to examine the association of CSF HSV PCR testing with length of stay (LOS) in a 20-center retrospective cohort of hospitalized infants aged ≤60 days undergoing evaluation for meningitis after adjustment for patient-level factors and clustering by center. Of 20,496 eligible infants, 7,399 (36.1%) had a CSF HSV PCR test performed, and 46 (0.6% of those tested) had a positive test. Infants who had a CSF HSV PCR test performed had a 23% longer hospital LOS (incident rate ratio 1.23; 95% CI: 1.14-1.33). Targeted CSF HSV PCR testing may mitigate the impact on LOS for low-risk infants.

<p><strong>OBJECTIVES: </strong>To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection.</p>

<p><strong>METHODS: </strong>In this 23-center nested case-control study, we matched 149 infants with HSV to 1340 controls; all were ≤60 days old and had cerebrospinal fluid obtained within 24 hours of presentation or had HSV detected. The primary and secondary outcomes were invasive (disseminated or central nervous system) or any HSV infection, respectively.</p>

<p><strong>RESULTS: </strong>Of all infants included , 90 (60.4%) had invasive and 59 (39.6%) had skin, eyes, and mouth disease. Predictors independently associated with invasive HSV included younger age (adjusted odds ratio [aOR]: 9.1 [95% confidence interval (CI): 3.4-24.5] &lt;14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with &gt;28 days), prematurity (aOR: 2.3, 95% CI: 1.1 to 5.1), seizure at home (aOR: 6.1, 95% CI: 2.3 to 16.4), ill appearance (aOR: 4.2, 95% CI: 2.0 to 8.4), abnormal triage temperature (aOR: 2.9, 95% CI: 1.6 to 5.3), vesicular rash (aOR: 54.8, (95% CI: 16.6 to 180.9), thrombocytopenia (aOR: 4.4, 95% CI: 1.6 to 12.4), and cerebrospinal fluid pleocytosis (aOR: 3.5, 95% CI: 1.2 to 10.0). These variables were transformed to derive the HSV risk score (point range 0-17). Infants with invasive HSV had a higher median score (6, interquartile range: 4-8) than those without invasive HSV (3, interquartile range: 1.5-4), with an area under the curve for invasive HSV disease of 0.85 (95% CI: 0.80-0.91). When using a cut-point of ≥3, the HSV risk score had a sensitivity of 95.6% (95% CI: 84.9% to 99.5%), specificity of 40.1% (95% CI: 36.8% to 43.6%), and positive likelihood ratio 1.60 (95% CI: 1.5 to 1.7) and negative likelihood ratio 0.11 (95% CI: 0.03 to 0.43).</p>

<p><strong>CONCLUSIONS: </strong>A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.</p>

<p><strong>OBJECTIVE: </strong>To assess the performance of a hemolytic uremic syndrome (HUS) severity score among children with Shiga toxin-producing Escherichia coli (STEC) infections and HUS by stratifying them according to their risk of adverse events. The score has not been previously evaluated in a North American acute care setting.</p>

<p><strong>STUDY DESIGN: </strong>We reviewed medical records of children &lt;18 years old infected with STEC and treated in one of 38 participating EDs in North America between 2011 and 2015. The HUS severity score [hemoglobin (g/dL) plus two-times serum creatinine (mg/dL)] was calculated using first available laboratory results. Children with scores &gt;13 were designated as high-risk. We assessed score performance to predict severe adverse events (ie, dialysis, neurologic complication, respiratory failure and death) using discrimination and net benefit (i.e. threshold probability), with subgroup analyses by age and day-of-illness.</p>

<p><strong>RESULTS: </strong>A total of 167 children had HUS, of whom 92.8% (155/167) had relevant data to calculate the score; 60.6% (94/155) experienced a severe adverse event. Discrimination was acceptable overall (AUC 0.71, 95% CI 0.63, 0.79) and better among children &lt;5 years old (AUC 0.77, 95% CI 0.68, 0.87). For children &lt;5 years, greatest net benefit was achieved for a threshold probability &gt;26%.</p>

<p><strong>CONCLUSIONS: </strong>The HUS severity score was able to discriminate between high- and low-risk children &lt;5 years old with STEC-associated HUS at a statistically acceptable level; however, it did not appear to provide clinical benefit at a meaningful risk threshold.</p>

<p><strong>BACKGROUND: </strong>Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care.</p>

<p><strong>METHODS: </strong>We conducted a multicenter, historical-cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children &lt;18 years who submitted STEC-positive specimens between January 2011 and December 2015 at a participating study institution were eligible.</p>

<p><strong>RESULTS: </strong>Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors of HUS included younger age (OR: 0.77; 95%CI: 0.69, 0.85/year), leukocyte count ≥13.0x103/μL (2.54; 1.42, 4.54), higher hematocrit (1.83; 1.21, 2.77/5% increase) and serum creatinine (10.82; 1.49, 78.69/1 mg/dL increase), platelet count &lt;250 ×103/μL (1.92; 1.02, 3.60), lower serum sodium (1.12; 1.02, 1.23/1 mmol/L decrease), and intravenous fluid administration initiated ≥4 days following diarrhea onset (2.50; 1.14, 5.46). A longer interval from diarrhea onset to index visit was associated with reduced HUS risk (0.70; 0.54, 0.90). RRT predictors included female sex (2.27; 1.14, 4.50), younger age (0.83; 0.74, 0.92/year), lower serum sodium (1.15; 1.04, 1.27/mmol/L decrease), higher leukocyte count ≥13.0x103/μL (2.35; 1.17, 4.72) and creatinine (7.75; 1.20, 50.16/1 mg/dL increase) concentrations, and initial intravenous fluid administration ≥4 days following diarrhea onset (2.71; 1.18, 6.21).</p>

<p><strong>CONCLUSIONS: </strong>The complex nature of STEC infection renders predicting its course a challenge. Risk factors we identified highlight the importance of avoiding dehydration and performing close clinical and laboratory monitoring.</p>

<p><strong>BACKGROUND: </strong>Although neonatal herpes simplex virus (HSV) is a potentially devastating infection requiring prompt evaluation and treatment, large-scale assessments of the frequency in potentially infected infants have not been performed.</p>

<p><strong>METHODS: </strong>We performed a retrospective cross-sectional study of infants ≤60 days old who had cerebrospinal fluid culture testing performed in 1 of 23 participating North American emergency departments. HSV infection was defined by a positive HSV polymerase chain reaction or viral culture. The primary outcome was the proportion of encounters in which HSV infection was identified. Secondary outcomes included frequency of central nervous system (CNS) and disseminated HSV, and HSV testing and treatment patterns.</p>

<p><strong>RESULTS: </strong>Of 26 533 eligible encounters, 112 infants had HSV identified (0.42%, 95% confidence interval [CI]: 0.35%-0.51%). Of these, 90 (80.4%) occurred in weeks 1 to 4, 10 (8.9%) in weeks 5 to 6, and 12 (10.7%) in weeks 7 to 9. The median age of HSV-infected infants was 14 days (interquartile range: 9-24 days). HSV infection was more common in 0 to 28-day-old infants compared with 29- to 60-day-old infants (odds ratio 3.9; 95% CI: 2.4-6.2). Sixty-eight (0.26%, 95% CI: 0.21%-0.33%) had CNS or disseminated HSV. The proportion of infants tested for HSV (35%; range 14%-72%) and to whom acyclovir was administered (23%; range 4%-53%) varied widely across sites.</p>

<p><strong>CONCLUSIONS: </strong>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.</p>