Daniela Burger, MD, Pediatric Hospital Medicine Fellow, Maimonides Infants & Children’s Hospital
Article: Andrea T. Cruz, Stephen B. Freedman, Dina M. Kulik, Pamela J. Okada, Alesia H. Fleming, et al. Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation. Pediatrics. 2018.
Summary: Cruz et al. conducted a large multi-center retrospective study of infants 0-60 days old to determine the prevalence of HSV infections in this neonatal population, as well as to describe HSV testing and empiric treatment practices across various tertiary-care institutions. Patients were identified at the time of ED encounter by using lab databases or available electronic health records that spanned 9 years between January 2005 and December 2013. Of the 26,533 ED encounters included in the study, HSV infection (CNS, SEM, and/or disseminated disease) was identified in 0.42% of all encounters, and in 1.2% of infants tested for HSV, with the highest frequency of infections found in the second week of life (median age 14 days). Frequency of HSV testing and empiric acyclovir therapy was highly variable between sites and did not correlate to the frequency of HSV infection at each respective site.
Key Strengths: This study was well powered to assess the primary outcome of neonatal HSV infection prevalence and included 23 tertiary-care emergency departments in various US states and Canadian provinces. The use of tertiary care centers also increased the likelihood of capturing patients who might re-present to another ED after the initial encounter because they might be transferred back to the tertiary care site.
Limitations: One limitation of the article is that the authors based their assessment of HSV infection prevalence on the assumptions that hospitalized children who did not receive empiric acyclovir would manifest symptoms of the infection and that patients who were discharged and developed HSV infection would re-present to the same ED or ultimately be transferred back to the ED included in the study. This leaves the possibility of some patients having HSV infection that were not counted due to not being tested, not manifesting symptoms during the original hospitalization, or subsequently presenting to outside institutions without being transferred back. The study also limited the inclusion of HSV testing to that which occurred within the first 24 hours of ED presentation, which also excludes the patients who received testing after the first 24 hours of presentation. Finally, the authors made note of the fact that similarities between the EDs at the included institutions precluded the analysis of hospital-level characteristics that might correlate with differences in HSV testing and treatment trends.
Major takeaway message: HSV infection in the first 60 days of life is rare, and even more so in the second month of life. However, testing and empiric therapy practices vary greatly between institutions and do not correlate to population infection frequencies.
Describe how this article should impact our practice: As we encounter febrile neonates, we must continue to weigh the risks of high mortality rates associated with delayed treatment of patients with HSV infection against the costs and potential iatrogenic complications of testing and treating uninfected infants. Future research is needed to identify clinical and laboratory factors that can assist with HSV infection risk stratification to more precisely test and treat high-risk neonates while avoiding unnecessary testing and treatment of those at low risk.
Article: Andrea T. Cruz, Stephen B. Freedman, Dina M. Kulik, Pamela J. Okada, Alesia H. Fleming, et al. Herpes Simplex Virus Infection in Infants Undergoing Meningitis Evaluation. Pediatrics. 2018.
Summary: Cruz et al. conducted a large multi-center retrospective study of infants 0-60 days old to determine the prevalence of HSV infections in this neonatal population, as well as to describe HSV testing and empiric treatment practices across various tertiary-care institutions. Patients were identified at the time of ED encounter by using lab databases or available electronic health records that spanned 9 years between January 2005 and December 2013. Of the 26,533 ED encounters included in the study, HSV infection (CNS, SEM, and/or disseminated disease) was identified in 0.42% of all encounters, and in 1.2% of infants tested for HSV, with the highest frequency of infections found in the second week of life (median age 14 days). Frequency of HSV testing and empiric acyclovir therapy was highly variable between sites and did not correlate to the frequency of HSV infection at each respective site.
Key Strengths: This study was well powered to assess the primary outcome of neonatal HSV infection prevalence and included 23 tertiary-care emergency departments in various US states and Canadian provinces. The use of tertiary care centers also increased the likelihood of capturing patients who might re-present to another ED after the initial encounter because they might be transferred back to the tertiary care site.
Limitations: One limitation of the article is that the authors based their assessment of HSV infection prevalence on the assumptions that hospitalized children who did not receive empiric acyclovir would manifest symptoms of the infection and that patients who were discharged and developed HSV infection would re-present to the same ED or ultimately be transferred back to the ED included in the study. This leaves the possibility of some patients having HSV infection that were not counted due to not being tested, not manifesting symptoms during the original hospitalization, or subsequently presenting to outside institutions without being transferred back. The study also limited the inclusion of HSV testing to that which occurred within the first 24 hours of ED presentation, which also excludes the patients who received testing after the first 24 hours of presentation. Finally, the authors made note of the fact that similarities between the EDs at the included institutions precluded the analysis of hospital-level characteristics that might correlate with differences in HSV testing and treatment trends.
Major takeaway message: HSV infection in the first 60 days of life is rare, and even more so in the second month of life. However, testing and empiric therapy practices vary greatly between institutions and do not correlate to population infection frequencies.
Describe how this article should impact our practice: As we encounter febrile neonates, we must continue to weigh the risks of high mortality rates associated with delayed treatment of patients with HSV infection against the costs and potential iatrogenic complications of testing and treating uninfected infants. Future research is needed to identify clinical and laboratory factors that can assist with HSV infection risk stratification to more precisely test and treat high-risk neonates while avoiding unnecessary testing and treatment of those at low risk.