title: Herpes PCR testing and empiric acyclovir use beyond the neonatal period.
abstract: BACKGROUND
  Diagnostic strategies based on empirical testing and treatment to identify herpes simplex virus (HSV) infection in neonates may not be appropriate for older children in whom the most common presentation of severe infection is encephalitis, a rare and clinically recognizable condition.
  
  
  METHODS
  Use of acyclovir in infants and children in 6 common non-HSV infection-related diagnosis-related groups was characterized between 1999 and 2012 at 15 US pediatric hospitals by using the Pediatric Health Information System database. Characteristics of non-neonatal patients at 1 institution tested for HSV encephalitis over a 6.5-year period were then analyzed to identify factors associated with potentially unnecessary testing and treatment.
  
  
  RESULTS
  Acyclovir use increased from 7.6% to 15.6% (P < .001) from 1999 to 2012. Much of this increase came in infants 30 to 60 days of age (82.7% increase, P < .001) and in patients with milder disease severity (44.8% increase, P < .001). Length of stay was increased by 2 days for children treated with acyclovir (P < .001). At our institution, 1394 HSV cerebrospinal fluid polymerase chain reactions were performed in children >30 days old, with only 3 positive results (0.22%). Comparison of the 3 subjects with positive testing and 55 with negative testing revealed that all cases, but only 4% (95% confidence interval 1.2%-14.0%) of noncases had clinical characteristics typical of HSV encephalitis.
  
  
  CONCLUSIONS
  Strategies for diagnosis and empirical treatment of suspected HSV encephalitis beyond the neonatal period have trended toward the approach common for neonates without evidence of an increase in disease incidence. This may result in increased medical costs and risk to patients.
authors.affiliation: Divison of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado; and james.gaensbauer@childrenscolorado.org.
authors.forename: James T
authors.initials: JT
authors.lastname: Gaensbauer
authors.affiliation: Department of Epidemiology, Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Meghan
authors.initials: M
authors.lastname: Birkholz
authors.affiliation: Department of Epidemiology, Children's Hospital Colorado, Aurora, Colorado.
authors.forename: Kari
authors.initials: K
authors.lastname: Pfannenstein
authors.affiliation: Divison of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine, Aurora, Colorado; and Department of Epidemiology, Children's Hospital Colorado, Aurora, Colorado.
authors.forename: James K
authors.initials: JK
authors.lastname: Todd
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage*; D016208:Databases, Factual / Q000592:standards / Q000639:trends; D036262:Empirical Research; D020803:Encephalitis, Herpes Simplex / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D016133:Polymerase Chain Reaction / Q000592:standards / Q000639:trends*; D018139:Simplexvirus / Q000187:drug effects* / Q000302:isolation & purification
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir
keywords: acyclovir; clinical medicine; diagnosis; empiricism; herpes simplex virus; meningoencephalitis