When it comes to thinking about an infant with possible meningitis in the first month of life, especially the first two weeks of life, neonatal herpes simplex virus (HSV) should be in the differential. But just because it’s in the differential, does that mean every infant we see with suspected meningitis should get HSV cultures and treatment with acyclovir? It would be important to get some sense of the prevalence of HSV in infants for whom meningitis is a concern, and this is just what Cruz et al. (10.1542/peds.2017-1688) have done in a new study being early released this month. The authors did a retrospective cross-sectional observational look at all infants less than 60 days of age who had cerebrospinal fluid testing performed in one of 23 pediatric emergency departments (EDs) over a 9 year period with HSV defined with a positive viral culture or polymerase chain reaction based on chart review (and not just a diagnostic code). Of the more than 26,000 infants in this study, only 112 had HSV positively identified with 90 cases found in the first month of life, and the remainder in the second 30 days. Given the infrequent occurrence of this virus, it should be no surprise that the range of testing for HSV in these EDs ran from 14 to 72 %, and acyclovir was given anywhere from 4-53% of the time. Even more concerning is that 16% of infants subsequently diagnosed with HSV did not receive empiric acyclovir. So what is the takeaway from this study?
The authors focus on the wide variability in testing and empiric treatment and call for better evidence-based approaches, but we wanted some additional perspective on this study, so we asked Drs. Sanjay Mahant from the Hospital for Sick Children, Jay Berry from Boston Children’s, and David Kimberlin from University of Alabama at Birmingham, all experts in evaluating the febrile infant with possible meningitis, to weigh in with a commentary (10.1542/peds.2017-3647). They point out a finding Cruz et al. share in that to ensure every infant with HSV got early treatment with acyclovir would require 237 infants without HSV to get the drug which can be associated with high cost and potential toxicity in young infants, although the authors of this study did not do a number needed to harm, just the number needed to treat. The commentary authors, like the study authors, call for evidence-based pathways or protocols to better define when testing or treatment is warranted in these infants as well as appropriate additional workup including blood and skin swabs for HSV PCR. Once we better understand who is truly high risk for HSV in being worked up for meningitis and who might not be, we will be closer to solving an over- and undertesting diagnostic dilemma that the study results call for more than ever before.