Objectives To analyse the performance of blood enterovirus and parechovirus PCR testing (ev-PCR) for invasive bacterial infection (IBI) (isolation of a single bacterial pathogen in a blood or cerebrospinal fluid culture) when evaluating well-appearing infants ≤90 days of age with fever without a source (FWS).

Methods We describe the well-appearing infants ≤90 days of age with FWS and normal urine dipstick. We performed a prospective, observational multicentre study at five paediatric emergency departments between October 2020 and September 2023.

Results A total of 656 infants were included, 22 (3.4%) of whom were diagnosed with an IBI (bacteraemia in all of them and associated with meningitis in four). The blood ev-PCR test was positive in 145 (22.1%) infants. One patient with positive blood ev-PCR was diagnosed with an IBI, accounting for 0.7% (95% CI 0.02 to 3.8) compared with 4.1% (95% CI 2.6 to 6.2) in those with a negative test (p=0.04). All four patients with bacterial meningitis had a negative blood ev-PCR result. Infants with a positive blood ev-PCR had a shorter hospital stay (median 3 days, IQR 2–4) compared with 4 days (IQR 2–6) for those with negative blood ev-PCR (p=0.02), as well as shorter duration of antibiotic treatment (median 2 days, IQR 0–4 vs 2.5 days, IQR 0–7, p=0.01).

Conclusions Young febrile infants with a positive blood ev-PCR are at a low risk of having an IBI. Incorporating the blood ev-PCR test into clinical decision-making may help to reduce the duration of antibiotic treatments and length of hospital stay.