Acyclovir dosing strategies in herpes encephalitis: A retrospective charts review

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BACKGROUND: Herpes encephalitis is a life-threatening condition that causes severe inflammation of the brain, often leading to permanent neurological damage or death if not treated promptly. Acyclovir is the main antiviral treatment for herpes encephalitis. Early use is essential to lower the risk of severe brain damage and improve survival rates. The objectives of this study were to describe the dosing of acyclovir in patients with suspected encephalitis and to determine the potential association between acyclovir dosage regimen and its safety and effectiveness. METHODS: A retrospective single-center observational study of patients admitted to the University of Alberta Hospital who received acyclovir and were suspected of having or diagnosed with herpes encephalitis. Patient charts were reviewed. Patient demographics, history of comorbidities, concomitant nephrotoxic medications, hospitalization department, length of hospital stay, acyclovir dosing, viral encephalitis diagnosis and outcomes were collected. Effectiveness outcomes included full recovery, partial recovery and death. Safety outcomes included the development of acute kidney injury (AKI) while on acyclovir treatment. We analyzed predictors of the outcomes using regression modeling. RESULTS: A total of 237 patients were included in the study. Among the patients who received acyclovir for more than 2 days, 88 (57 %) patients received an adequate dose, 54 (35 %) patients received sub-therapeutic dosage regimen and 12 (8 %) patients received supra-therapeutic regimen. Older age was associated with less favorable outcomes (adjusted odds ratio (OR) 1.05, 95 % Confidence Interval (CI) 1.01-1.09, p = 0.02). Additionally, there was a trend suggesting that herpes simplex virus type 1 (HSV-1) resulted in the worst outcomes, with the highest percentage of unfavorable outcomes observed in the sub-therapeutic dosing group. In contrast, supra-therapeutic dose of acyclovir was significantly associated with AKI (adjusted OR 12.9, 95 %CI 3.14-53.07, p < 0.001). CONCLUSION: Our study suggests that administering acyclovir based on actual body weight for non-obese patients and adjusted body weight for obese patients may enhance outcomes by promoting recovery and preventing toxicity. Multicenter prospective studies are needed to confirm such association and to provide clear guidelines of the most appropriate dosing of acyclovir in herpes encephalitis.

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