Neonatal Herpes Simplex Virus Disease

Patient Population: Pediatric
Condition Major Pathogens  First-choice Therapy Alternative Therapy Comments

Neonatal herpes simplex disease - disseminated, CNS/encephalitis, or mucocutaneous (skin/eye/mouth) (including young infants < 3 months old) 

Consider diagnosis in infants with cutaneous vesicles, seizure, focal neurologic signs, CSF pleocytosis, unexplained thrombocytopenia or hepatitis 

See guidance on HSV disease in older pediatric patients 

Herpes simplex virus 

Acyclovir 20 mg/kg/dose IV q8h 

All infants with neonatal HSV disease should receive suppressive therapy following completion of above treatment course, for a minimum 6 months: 

Acyclovir 300 mg/m2/dose enterally tid  


ID consult recommended 

All infants with suspected or proven neonatal HSV disease should have a full evaluation with LP, CSF HSV PCR, plasma HSV PCR, cultures or PCR of conjunctivae, mouth, nasopharynx, and rectum  

Consider  ophthalmologic examination and neuroimaging for infants diagnosed with neonatal HSV disease  

Ocular HSV requires addition of topical antivirals  (trifluridine or ganciclovir gel) and ophthalmology co-management 

Skin/eye/mouth disease: 14 days 

CNS disease: Minimum of 21 days (repeat LP near end of therapy, duration extended if HSV still detected in CSF) 

Disseminated disease: 21 days 

Asymptomatic infant born to mother with active HSV lesions    Refer to published guidelines, or consult ID     


American Academy of Pediatrics. In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. 32nd ed. Elk Grove Village, IL: American Academy of Pediatrics; 2021.  

Kimberlin DW, Baley J, Committee on Infectious Diseases, et al. Guidance on management of asymptomatic neonates born to women with active genital herpes lesions. Pediatrics 2013;131:383–6.

Pediatric Empiric Antimicrobial Therapy Guidelines

This is a subsection of the UCSF Benioff Children’s Hospitals Empiric Antimicrobial Therapy Guidelines, developed by the Pediatric Antimicrobial Stewardship Programs at each campus to inform initial selection of empiric antimicrobial therapy for children at the UCSF Benioff Children’s Hospitals and affiliated outpatient sites. 

These are guidelines only and not intended to replace clinical judgment. Modification of therapy may be indicated based on patient comorbidities, previous antibiotic therapy or infection history. Doses provided are usual doses but may require modification based on patient age or comorbid conditions. Refer to Pediatric Antimicrobial Dosing Guideline for further guidance on dosing in children, and Neonatal Dosing Guideline for infants < 1 month of age. Consult a pediatric pharmacist for individualized renal or hepatic dose adjustment. Durations provided are usual recommendations for patients who are responding appropriately to therapy. For additional guidance, please contact Pediatric Infectious Diseases (ID) or the Pediatric Antimicrobial Stewardship Program (ASP) at the campus where your patient is receiving care.  

For questions or feedback about these guidelines, please email primary content owners, Rachel Wattier, Pediatric ASP Medical Director at BCH SF and Prachi Singh, Pediatric ASP Medical Director at BCH OAK. 

The content of these guidelines was updated in July 2021. See Summary and Rationale for Changes (password login to Box needed) for detailed explanations of the content changes.