Introduction:In neonates and young infants, it can be diffi cult to distinguish bacterial from aseptic meningitis, especially in the setting of marked CSF (cerebrospinal fl uid) pleocytosis. This case series and review of the literature explores the role of early CSF EV-PCR (enterovirus-polymerase chain reaction) in these patients' diagnostic workup, management, and overall hospital stay.Case Series: Patient 1 was a 30-day-old female who presented with a fever of 102°F and increased irritability for 1 day. She was admitted to the hospital for an evaluation including complete blood cell count (CBC), blood culture, urine culture, urinalysis, and lumbar puncture (LP). Ampicillin, gentamicin, and acyclovir were initiated. Admission laboratory data included peripheral white blood cell (WBC) count of 9200 cells/µL and a normal urinalysis. Cerebrospinal fl uid (CSF) was remarkable for pleocytosis of 1005 cells/µL with 53% lymphocytes, 0 red blood cells (RBCs), protein of 92.8 mg/dL, and glucose of 44 mg/dL (Table 1). Gram-stain of the CSF revealed Gram-positive cocci in pairs; however, no bacteria were cultured. Results of the urine culture were negative. The blood culture grew coagulase-negative Staphylococcus, which was believed to be a contaminant. The patient continued to be febrile despite 72 hours of antibiotic therapy. Therefore, a repeat LP was performed, revealing 80 WBC/µL with 63% lymphocytes, 700 RBC/µL, protein of 138 mg/dL, and glucose of 38 mg/dL. Enterovirus-polymerase chain reaction (EV-PCR) performed on the repeat CSF was positive. Herpes simplex virus polymerase chain reaction (PCR) was negative. Antibiotic therapy was discontinued, and the patient was discharged from the hospital.