Factors associated with delay to acyclovir administration in 184 patients with herpes simplex virus encephalitis

Abstract

The main predictor of outcomes in herpes simplex virus (HSV) encephalitis (HSE) is the delay between hospital admission and initiation of acyclovir. In this study, factors associated with late initiation of acyclovir were identified. The study included adults from northern France whose cerebrospinal fluid (CSF) was positive for HSV by PCR. Late initiation of acyclovir was defined as a delay of >1 day from hospital admission. In total, 184 patients were retrospectively enrolled from January 1991 to December 2002. The median age was 60 years (range: 17-91), and 102 (55.4%) were male. Acyclovir was initiated >1 day after hospital admission in 68 patients (37.0%). According to multivariate analysis, independent risk factors for late initiation of acyclovir were severe underlying disease (Knaus score >or=C) (OR 4.1; 95% CI 1.5-11.7); alcohol abuse (OR 3.4; 95% CI 1.3-8.9); and a delay of >1 day from admission to first brain imaging (OR 8.4; 95% CI 3.9-18.0). In addition, univariate analysis suggested an association between a finding of <10 leukocytes/mm(3) in CSF at admission (OR 2.5; 95% CI 0.7-5.8). These characteristics were found in 26 (14.1%), 23 (12.5%), 66 (35.9%) and 27 (14.7%) patients, respectively. One risk factor was identified in 109 (59.2%) patients, two in 29 (15.8%), and three in six (3.3%). Patients with HSE often present with severe underlying disease, chronic alcohol abuse, or atypical CSF findings, and such factors should not be allowed to delay diagnosis and administration of acyclovir.

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management

“…Kim et al [160] recently retrospectively reviewed 29 patients with PCR-proven HSVE and found that severe EEG abnormalities were predictive of poor outcome at 6 months, although this was not observed in a series of 45 patients from the Mayo Clinic [57]. Early recognition and timely administration of aciclovir are critically important for improving outcomes, and late administration of aciclovir is the most readily modifiable risk factor for poor outcomes [62,63,161,162]. Factors contributing to delayed treatment include immunocompromise [63], severe comorbid disease, history of alcohol abuse, absence of fever, and CSF leukocytes <10/ml [162].…”

“…Early recognition and timely administration of aciclovir are critically important for improving outcomes, and late administration of aciclovir is the most readily modifiable risk factor for poor outcomes [62,63,161,162]. Factors contributing to delayed treatment include immunocompromise [63], severe comorbid disease, history of alcohol abuse, absence of fever, and CSF leukocytes <10/ml [162].…”

Méningites purulentes et méningoencéphalites graves (à l’exclusion des patients immunodéprimés)

“…Il a été montré une relation entre la pré-cocité du traitement antiviral par aciclovir et le pronostic. Les facteurs associés à un traitement tardif sont un tableau atypique et le retard à la réalisation de l'imagerie [33]. La ME typique, et d'ailleurs habituelle, est une maladie aiguë survenant chez des individus sans terrain particulier.…”

Neuro-Intensive Care of Patients with Acute CNS Infections

“…In patients with suspected bacterial meningitis, as well as encephalitis, empiric antibiotic therapy should be initiated after blood cultures are completed if lumbar puncture is delayed for neuroimaging (see previously). Empiric acyclovir therapy should also be initiated in patients with suspected Herpes simplex encephalitis, pending results of diagnostic studies [38,44].…”

“…In a recent retrospective review of 184 patients with HSV encephalitis, 37% of patients received acyclovir late in the hospitalization (>1 day after admission) [44]. Late administration of acyclovir was associated with severe underlying disease, alcohol abuse, atypical CSF features (<10 WBCs), and a delay of >1 day in neuroimaging [44].…”