Clinical characteristics, antimicrobial therapy, and outcomes in febrile infants with and without human parechovirus detected in cerebrospinal fluid

Background: Human parechovirus (HPeV) infection in infants aged <4 months can present with sepsis-like symptoms, making it challenging to distinguish from bacterial infection. Although previous studies have described the clinical features of HPeV infection in young infants, comparative data on clinical characteristics, duration of antimicrobial therapy, length of hospital stay, and clinical outcomes between HPeV-positive and HPeV-negative febrile infants remain limited. In Japan, the FilmArray ®︎ meningitis/encephalitis panel has been reimbursed by national health insurance system since September 2022, but its clinical utility for the management of febrile young infants has not yet been well characterized in the Japanese clinical setting. Therefore, we compared the clinical characteristics and outcomes of febrile infants with and without HPeV detection using the FilmArray ® meningitis/encephalitis panel. Methods: Between April and November 2023, 25 febrile infants aged <4 months (median age, 40 days) underwent cerebrospinal fluid (CSF) testing using the FilmArray ® meningitis/encephalitis panel. In this retrospective cohort study, patients were classified into HPeV-positive (n=9) and HPeV-negative (n=16) groups based on HPeV detection in CSF using the panel. Clinical symptoms, physical findings, laboratory data, duration of antimicrobial therapy, and length of hospital stay were retrospectively extracted from medical records. The Wilcoxon two-sample test and Fisher’s exact test were used for between-group comparisons. Results: The median ages were 31 and 37 days in the HPeV-positive and HPeV-negative groups, respectively. There were no significant differences in age, sex, or other baseline characteristics between the two groups. Compared with the HPeV-negative group, the HPeV-positive group more frequently exhibited abdominal distension (78% vs. 6%, P<0.001), reticular cyanosis (67% vs. 13%, P=0.009), and palmar-plantar erythema (44% vs. 0%, P=0.01). At admission, white blood cell counts (median, 4,310 vs. 9,090 /μL, P=0.02) and C-reactive protein levels (0.24 vs. 0.91 mg/dL, P=0.01) were significantly lower in the HPeV-positive group. Although the duration of fever tended to be longer in the HPeV-positive group (48 vs. 30 hours, P=0.13), the duration of antimicrobial therapy was significantly shorter (62 vs. 85 hours, P=0.02). No significant difference was observed in the length of hospital stay (6 vs. 7 days, P=0.09). Conclusions: In this small, single-center study, HPeV-positive febrile infants received a shorter duration of antimicrobial therapy than HPeV-negative infants. Rapid identification of HPeV using the FilmArray ® meningitis/encephalitis panel may support appropriate antimicrobial use in febrile young infants. However, HPeV detection alone does not exclude bacterial infection, and larger studies are needed to determine the impact of rapid HPeV identification on antimicrobial management.