Predictors of Invasive Herpes Simplex Virus Infection in Young Infants.

OBJECTIVES: To identify independent predictors of and derive a risk score for invasive herpes simplex virus (HSV) infection. METHODS: 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. RESULTS: 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] <14 and 6.4 [95% CI: 2.3 to 17.8] 14-28 days, respectively, compared with >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). CONCLUSIONS: A novel HSV risk score identified infants at extremely low risk for invasive HSV who may not require routine testing or empirical treatment.

The Champagne Tap: Time to Pop the Cork?

BACKGROUND: A "champagne tap" is a lumbar puncture with no cerebrospinal fluid (CSF) red blood cells (RBCs). Clinicians disagree whether the absence of CSF white blood cells (WBCs) is also required. AIMS: As supervising providers frequently reward trainees after a champagne tap, we investigated how varying the definition impacted the frequency of trainee accolades. MATERIALS & METHODS: We performed a secondary analysis of a retrospective cross-sectional study of infants ≤60 days of age who had a CSF culture performed in the emergency department (ED) at one of 20 centers participating in a Pediatric Emergency Medicine Collaborative Research Committee (PEM CRC) endorsed study. Our primary outcomes were a champagne tap defined by either a CSF RBC count of 0 cells/mm3 regardless of CSF WBC count or both CSF RBC and WBC counts of 0 cells/mm3 . RESULTS: Of the 23,618 eligible encounters, 20,358 (86.2%) had both a CSF RBC and WBC count obtained. Overall, 3,147 (13.3%) had a CSF RBC count of 0 cells/mm3 and 377 (1.6%) had both CSF WBC and RBC counts of 0 cells/mm3 (relative rate 8.35, 95% confidence interval 7.51 to 9.27). CONCLUSIONS: In infants, a lumbar puncture with a CSF RBC count of 0 cells/mm3 regardless of the CSF WBC count occurred eight-times more frequently than one with both CSF WBC and RBC counts of 0 cells/mm3 . A broader champagne tap definition would allow more frequent recognition of procedural success, with the potential to foster a supportive community during medical training, potentially protecting against burnout.

Association of Herpes Simplex Virus Testing with Hospital Length of Stay for Infants ≤60 Days of Age Undergoing Evaluation for Meningitis.

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.

Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Impact of Enteroviral Polymerase Chain Reaction Testing on Length of Stay for Infants 60 Days Old or Younger.

OBJECTIVE: To determine the impact of a cerebrospinal fluid enterovirus polymerase chain reaction (PCR) test performance on hospital length of stay (LOS) in a large multicenter cohort of infants undergoing evaluation for central nervous system infection. STUDY DESIGN: We performed a planned secondary analysis of a retrospective cohort of hospitalized infants ≤60 days of age who had a cerebrospinal fluid culture obtained at 1 of 18 participating centers (2005-2013). After adjustment for patient age and study year as well as clustering by hospital center, we compared LOS for infants who had an enterovirus PCR test performed vs not performed and among those tested, for infants with a positive vs negative test result. RESULTS: Of 19 953 hospitalized infants, 4444 (22.3%) had an enterovirus PCR test performed and 945 (21.3% of tested infants) had positive test results. Hospital LOS was similar for infants who had an enterovirus PCR test performed compared with infants who did not (incident rate ratio 0.98 hours; 95% CI 0.89-1.06). However, infants PCR positive for enterovirus had a 38% shorter LOS than infants PCR negative for enterovirus (incident rate ratio 0.62 hours; 95% CI 0.57-0.68). No infant with a positive enterovirus PCR test had bacterial meningitis (0%; 95% CI 0-0.4). CONCLUSIONS: Although enterovirus PCR testing was not associated with a reduction in LOS, infants with a positive enterovirus PCR test had a one-third shorter LOS compared with infants with a negative enterovirus PCR test. Focused enterovirus PCR test use could increase the impact on LOS for infants undergoing cerebrospinal fluid evaluation.

Correction of Cerebrospinal Fluid Protein in Infants With Traumatic Lumbar Punctures.

In our multicenter cohort of infants ≤60 days of age, we identified 2646 infants with a traumatic lumbar puncture, of which 31 (1.2%) had bacterial meningitis. For every 1000 cerebrospinal fluid red blood cells/mm, cerebrospinal (cerebrospinal fluid) protein increased 1.1 mg/dL (95% confidence interval: 1.0-1.2 mg/dL).