Impact of a Rapid Herpes Simplex Virus PCR Assay on Duration of Acyclovir Therapy

Abstract

Herpes simplex virus (HSV) infections of the central nervous system (CNS) are associated with significant morbidity and mortality rates in children. This study assessed the impact of a direct HSV (dHSV) PCR assay on the time to result reporting and the duration of acyclovir therapy for children with signs and symptoms of meningitis and encephalitis. A total of 363 patients with HSV PCR results from cerebrospinal fluid (CSF) samples were included in this retrospective analysis, divided into preimplementation and postimplementation groups. For the preimplementation group, CSF testing was performed using a laboratory-developed real-time PCR assay; for the postimplementation group, CSF samples were tested using a direct sampleto-answer assay. All CSF samples were negative for HSV. Over 60% of patients from both groups were prescribed acyclovir. The average HSV PCR test turnaround time for the postimplementation group was reduced by 14.5 h (23.6 h versus 9.1 h; P Ͻ 0.001). Furthermore, 79 patients (43.6%) in the postimplementation group had dHSV PCR results reported Ͻ4 h after specimen collection. The mean time from specimen collection to acyclovir discontinuation was 17.1 h shorter in the postimplementation group (31.1 h versus 14 h; P Ͻ 0.001). The median duration of acyclovir therapy was also significantly reduced in the postimplementation group (29.2 h versus 14.3 h; P ϭ 0.01). Our investigation suggests that implementation of rapid HSV PCR testing can decrease turnaround times and the duration of unnecessary acyclovir therapy.KEYWORDS HSV, acyclovir, encephalitis, herpes simplex virus, meningitis, rapid diagnosis, toxicity H erpes simplex viruses (HSVs) are important causes of meningitis and encephalitis, particularly among children and immunocompromised patients (1). The HSV infection rate among neonates is estimated to be 1 case per 32,000 deliveries, and approximately 1,500 cases of neonatal HSV disease occur annually in the United States (2, 3). Prompt initiation of antiviral therapy is paramount, as mortality rates for disseminated neonatal infections can be as high as 80% if the infections are left untreated; 70% of survivors are left with detrimental neurological sequelae (4-6).Patients with HSV meningitis and encephalitis typically have initial presentations of headache, fever, and altered mental status. However, neonates with HSV central nervous system (CNS) infections may have nonspecific presentations, including lethargy, irritability, poor oral intake, and temperature instability (7). Cutaneous vesicular lesions may be indicative of HSV infections in infants, but the absence of vesicular rash does not preclude neonatal HSV CNS infection in 35% of cases (8). Other infectious etiologies associated with CNS infections can present with similar symptoms (9). Thus, laboratory testing of cerebrospinal fluid (CSF) samples is necessary to confirm the diagnoses.

Comparison of antibiotic and acyclovir usage before and after the implementation of an on-site FilmArray meningitis/encephalitis panel in an academic tertiary pediatric hospital: a retrospective observational study

“…Our results suggest that the implementation of rapid molecular testing for meningoencephalitis in pediatric hospitals can lead to earlier optimization of empiric therapy, as seen in several recent studies [26][27][28][29]. However, in contrast to our study, these reports refer to single PCR assays.…”

Rapid Molecular Panels: What Is in the Best Interest of the Patient? A Review of Patient Outcome Studies for Multiplex Panels Used in Bloodstream, Respiratory, and Neurological Infections

“…However, data supporting the benefit of molecular RDTs in these cases are scarce. Using a retrospective quasi-experimental study design, Van and colleagues [20] recently described the effect of switching from the realStar alphaherpesvirus PCR kit, a multiplex PCR LDT that detects HSV-1, HSV-2, and varicella zoster virus, (alTona Diagnostics, Hamburg, Germany) that was performed once per day, 6 days per week, to the Simplexa HSV 1 and 2 Direct assay, which was performed on demand, 24 hours per day, 7 days per week. This study did not report any positive results, but among their 182 patients with suspected meningitis and/or encephalitis who were tested prior to rapid testing and 181 patients tested post-implementation, the study reported a decrease in the median duration of acyclovir therapy from 29.2 hours to 14.3 hours.…”

“…This study did not report any positive results, but among their 182 patients with suspected meningitis and/or encephalitis who were tested prior to rapid testing and 181 patients tested post-implementation, the study reported a decrease in the median duration of acyclovir therapy from 29.2 hours to 14.3 hours. The authors felt that, given evidence that renal toxicity and neurotoxicity typically occur within the first 48 hours of intravenous acyclovir administration, this reduction in acyclovir use associated with rapid HSV-1/HSV-2 testing had the potential to be clinically impactful [20].…”

Update Opportunistic Infections of the Central Nervous System in Patients with Iatrogenic Immunosuppression

“…CSF analysis reveals lympho-monocytic pleocytosis, slightly increased protein levels and HSV-positive polymerase chain reaction [38][39][40].…”