Snapshot A 36-year-old man presents to the emergency department with lethargy and confusion. His symptoms began approximately 2 days ago when he experienced a headache, memory impairment, vomiting, and fever. His temperature is 101°F (38.3°C), blood pressure is 144/95 mmHg, pulse is 104/min, and respirations are 18/min. The patient has an altered level of consciousness on the physical exam. A non-contrast CT scan of the head is unremarkable. A lumbar puncture is performed and the patient is started on antibiotics. Cerebrospinal fluids results return with a mononuclear pleocytosis, elevated red blood cells and protein, and normal glucose. A polymerase chain reaction (PCR) is positive for herpes simplex virus 2. The patient's empiric treatment has been narrowed to acyclovir. (Herpes simplex encephalitis) Introduction Mechanism of action acyclovir is phosphorylated by a virally-encoded thymidine kinase acyclovir triphosphate acts as a guanosine analog, which impairs viral DNA polymerase, impairing viral DNA synthesis acyclovir is not phosphorylated in uninfected cells, resulting in a favorable adverse effect profile Mechanism of resistance altered virally-encoded thymidine kinase altered viral DNA polymerase Clinical use herpes simplex virus 1 and 2 infection varicella-zoster virus Adverse effects acute renal failure acyclovir can precipitate into crystals in the renal tubules slow drug infusion and pre-hydration decreases this risk