Neonatal Herpes Infection: A Review

Leslie A. Parker, MSN, RNC, NNP; Sheryl J. Montrowl, MSN, RNC, NNP


NAINR. 2004;4(1) 

In This Article


In the late 1970s effective antivirals for treating neonatal HSV were beginning to be used and have since been shown to ameliorate this disease. The first available drug, virdarabine, was studied extensively in the 1980s.[32,48] By the end of the decade a study comparing virdarabine and acyclovir showed the latter to be just as effective in treating neonatal HSV.[32,49] Acyclovir quickly replaced virdarabine as the drug of choice because of its ease of use.[50] There have been a few case reports of newborns with acyclovir-resistant HSV infection. Although this is rare, it must be suspected in those infants who do not respond appropriately or who deteriorate after initial clinical improvement on acyclovir therapy. In these cases foscarnet can be substituted effectively.[11,40,51]

Acyclovir is used for the prevention and treatment of HSV and varicella infections and is available in intravenous or oral forms, although there is limited data for oral use in the newborn. Tod and coworkers[52] published a study in 2001 describing the pharmacokinetics of oral acyclovir in newborns and children. In this study the inhibitory concentration of acyclovir was greater than 50% for 12 hour during a 24 hour period, thus showing that oral dosing for newborns at 24 mg/kg/g8h is adequate for treating HSV infections.[52] The current recommendation, however, is that acyclovir be administered intravenously.[2]

Acyclovir was approved by the Food and Drug Administration for use in treating neonatal HSV in June 1998.[50] It is a DNA chain terminator and acts as a competitive inhibitor of HSV DNA polymerase.[6,10,53] Acyclovir can cause renal toxicity but this can be prevented or reversed with good hydration. It has also been associated with CNS toxicity when using high doses in the presence of renal failure. Other side effects include nausea, vomiting, and diarrhea.[54] Acyclovir is ineffective in latent infections and does not eradicate virus from the ganglia.[11]

Traditionally the standard dose of acyclovir was 30 mg/kg/day divided three times per day. In 2001 Kimberlin and coworkers[50] published a paper summarizing the work of The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group from 1981 to 1997. They briefly described the initial study done during the period 1981 to 1988 showing the safety and efficacy of acyclovir in the treatment of neonatal HSV using standard doses. Continued high mortality and morbidity despite standard therapy for 10 days led to the second study comparing intermediate doses (45 mg/kg/day) of acyclovir with high doses (60 mg/kg/day) for safety, toxicity, and effectiveness. This study, conducted between 1989 to 1997, supported the use of high dose acyclovir and recommended treatment doses are now 60 mg/kg/day divided three times per day for 21 days in Central Nervous System (CNS) and disseminated disease and 14 days for SEM disease.[2,39,50] The most significant side effect of high dose acyclovir was neutropenia, but the study was inconclusive as to whether the severity of disease or the actual dosing was the cause. Neutropenia in all patients resolved during continuation of treatment or after the course and there were apparently no side effects of the neutropenia.[50] Grade three or four nephrotoxicity occurred in only 6% of the patients treated with high dose, and this also could have been attributed to the severity of the disease. In addition, high dose acyclovir was shown not to impede antibody response. There was a statistical significance in mortality in patients with disseminated disease treated with standard and high dosing. Mortality with standard dosing was 61%, intermediate dosing was 57%, and high dosing was 31%.


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