Case Presentation: A 13 day-old term male presented in the summer with one day of fever and irritability. Prenatal course and delivery were normal. On initial exam he was febrile and irritable but easily consoled. Blood, urine, and cerebrospinal fluid (CSF) bacterial cultures were obtained, and cefepime and ampicillin were started. CSF had no organisms on gram stain, elevated protein (64 mg/dL), normal glucose, 1 total nucleated cell, and 1150 red blood cells. Urinalysis, complete blood count, and comprehensive metabolic panel were normal. Shortly after admission, he continued to be febrile but then developed persistent tachycardia, delayed capillary refill, and increased lethargy. Herpes simplex virus (HSV), enterovirus, and human parechovirus (HPeV) PCR testing were obtained, and IV acyclovir was started. After multiple fluid resuscitation attempts but no clinical improvement, he was transferred to the pediatric intensive care unit (PICU) for severe sepsis. Chest x-ray had no focal consolidation or effusion. HPeV PCR was positive in CSF, blood, and rectal swab. At 48 hours, blood, urine and CSF cultures along with HSV and enterovirus PCR testing were negative, and antimicrobials were discontinued. EKG showed frequent premature ventricular contractions (PVCs) and troponin-I was elevated (0.038 ng/mL). Findings were consistent with myocarditis; echocardiogram showed preserved cardiac output and systolic function. PVC frequency gradually decreased, and vasopressors were never required. Due to encephalopathy, he was placed on continuous EEG monitoring which showed multifocal spikes; levetiracetam was started for high risk of seizures. After two subclinical seizures on the 4th day of hospitalization, phenobarbital was started and the levetiracetam dose was increased. No clinical or subclinical seizures occurred thereafter. Brain MRI was within normal limits. The final diagnosis was determined to be HPeV myocarditis and meningoencephalitis.
Discussion: Enterovirus and HPeV infections are frequently seen by hospitalists, and there is a wide scale of disease severity. Severe neonatal infection can cause sepsis, hepatitis, pneumonia, myocarditis, and meningoencephalitis (which can occur without CSF pleocytosis). Neonates with both myocarditis and hepatitis have the highest risk of mortality. Mothers often have symptoms of a viral illness just before or after delivery. Neurologic deterioration and severe neurodevelopmental delay can be sequelae of neonatal HPeV meningoencephalitis. There is no approved antiviral treatment for HPeV, but intravenous immunoglobulin has been used in some severe cases.
Conclusions: The management of a febrile neonate goes beyond starting empiric antimicrobials, and tachycardia is not always secondary to fever alone. Tachycardia that persists despite fluid resuscitation warrants assessment for cardiac compromise. It is important to recognize the spectrum of neonatal enterovirus/HPeV disease. These infections are typically innocuous, but keen clinical acumen and a high degree of suspicion are needed to detect life-threatening cases. Awareness of viral sepsis complications is imperative and requires escalation of care in facilities with the resources to detect and treat potential adverse outcomes.