Delayed Acyclovir Therapy and Death Among Neonates With Herpes Simplex Virus Infection
Open accessAbstract
OBJECTIVE: To determine the association of delayed acyclovir therapy with death among neonates with herpes simplex virus (HSV) infection. METHODS: A multicenter, retrospective, cohort study was conducted between January 1, 2003, and December 31, 2009, with 1086 neonates (age: ≤28 days) with HSV infection from 41 tertiary care children's hospitals. Early acyclovir therapy was defined as initiation of intravenous acyclovir treatment within 1 day after hospital admission, and delayed acyclovir therapy was defined as initiation of treatment >1 and ≤7 days after hospital admission. Multivariate logistic regression models determined the association between delayed acyclovir therapy and death, with the use of propensity scores for each neonate's likelihood of receiving delayed acyclovir treatment to control for differences in illness severity between groups. RESULTS: The median age was 10 days. Delayed acyclovir therapy was administered to 262 neonates (24.1%). In most cases (86.2%) of delayed receipt, acyclovir administration occurred on the second or third day of hospitalization. The overall mortality rate was 7.3% (95% confidence interval: 5.8%–9.0%); 9.5% of those who received delayed acyclovir treatment and 6.6% of those who received early acyclovir treatment died. In a multivariate analysis, delayed acyclovir therapy was associated with significantly greater odds of death (adjusted odds ratio: 2.63 [95% confidence interval: 1.36–5.08]) compared with early acyclovir therapy. CONCLUSIONS: In this multicenter observational study of neonates with HSV infection, delayed initiation of acyclovir therapy was associated with in-hospital death. Our data support the use of empiric acyclovir therapy for neonates undergoing testing for HSV infection.
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Delays in CSF testing can have significant clinical consequences if therapy is delayed or incorrectly administered.
“This leads to delays, which can have significant clinical consequences if therapy is delayed or incorrectly administered (9–11).”
From Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens (2016) · cites this paper as [9]
The Outcome Measures passage reports that death rates rose with each additional day before acyclovir treatment began in neonates with HSV infection. The paper does not establish that delays in CSF testing caused treatment delays, and it does not examine incorrectly administered therapy as an outcome. No page numbers are available in our copy. (LLM, conf=0.83)
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- [1]1. Cohen DM, Lorch SA, King RL, Hodinka RL, Cohn KA, Shah SS. Factors influencing the decision to test young infants for herpes simplex virus infection. Pediatr Infect Dis J . 2007;26(12):1156-1158
- [2]2. Caviness AC, Demmler GJ, Almendarez Y, Selwyn BJ. The prevalence of neonatal herpes simplex virus infection compared with serious bacterial illness in hospitalized neonates. J Pediatr . 2008;153(2):164-169
- [3]3. Whitley RJ, Nahmias AJ, Soong SJ, Galasso GG, Fleming CL, Alford CA. Vidarabine therapy of neonatal herpes simplex virus infection. Pediatrics . 1980;66(4):495-501
- [4]4. Kimberlin DW, Lin CY, Jacobs RF, et al. Natural history of neonatal herpes simplex virus infections in the acyclovir era. Pediatrics . 2001;108(2):223-229
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Initial Presentation of Neonatal Herpes Simplex Virus Infection
Curfman, A. L., Glissmeyer, E. W., Ahmad, F. A., Korgenski, E. K., Blaschke, A. J., Byington, C. L., & Miller, A. S. (2016) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2016.02.015 · Cited by 73 · see citing works
Bårnes, G. K., Gudina, E. K., Berhane, M., Abdissa, A., Tesfaw, G., Abebe, G., Feruglio, S. L., Caugant, D. A., & Jørgensen, H. J. (2018) · BMC Infectious Diseases · doi:10.1186/s12879-018-3589-4 · Cited by 37 · see citing works
- Authors
- Shah, S. S., Aronson, P. L., Mohamad, Z., & Lorch, S. A.
- Affiliations
- Divisions of Infectious Diseases,
- Departments of Pediatrics and
- Emergency Medicine, and
- Children's Hospital of Philadelphia (US)
- Venue
- Pediatrics
- Publisher
- American Academy of Pediatrics (AAP)
- Published
- 2011-12-01
- Volume
- 128
- Issue
- 6
- Pages
- 1153-1160
- ISSN
- 0031-4005 (ISSN-L)
- 1098-4275
- PMC
- PMC3387895
- OpenAlex
- W2133759854
- Cited by
- 92
- References
- 0
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 7 · 2023: 3 · 2022: 6 · 2021: 7 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 8 · 2016: 6 · 2015: 5 · 2014: 9 · 2013: 7 · 2012: 4
- FWCI
- 4.82
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- PEDIATRICS (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Robert Wood Johnson Foundation (K01 AI73729)
- National Institutes of Health (K01 AI73729)
- National Institute of Allergy and Infectious Diseases (K01AI073729, K01-AI-73729)
- Topics
- Health Sciences › Medicine › Epidemiology › Herpesvirus Infections and Treatments
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Neonatal and Maternal Infections
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- neonatal herpes simplex virus infection, acyclovir, treatment timing, mortality, empiric antiviral therapy, intravenous acyclovir
- MeSH terms
- Acyclovir, Antiviral Agents, Female, Herpes Simplex, Humans, Infant, Newborn, Male, Retrospective Studies, Time Factors, Cohort Studies
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