A International Multicentre observational study to validate clinical practice guidelines for management of febrile infants aged ≤90 days

Background
Fever is one of the most common reasons for infants to attend Paediatric Emergency Departments (PED) in the UK and Ireland.1,2 Identifying young infants with serious bacterial infection (SBI) from those with benign viral infections is extremely difficult.2 3 Between 8%-20.5% of febrile infants ≤90 days have SBI, of which UTI is most common.4 5 1–2% of these infants have invasive bacterial infection associated with significant morbidity and mortality if unrecognised.3 4 Clinical decision tools have been shown to reduce practice variation and optimise outcome as well as cost.6 Neither of the two currently available national guidelines, National Institutes for Health and Care Clinical Excellence (NICE) Sepsis NG51 or Feverish illness NG143 have been validated in this cohort.

Objectives
To validate existing Clinical Practice Guidelines (CPG) for the detection of SBI in infants <90 days with fever in the UK and Ireland.

Methods
The Febrile Infants Diagnostic Assessment and Outcome (FIDO) study was a retrospective multicentre (Belfast, Bristol, Dublin, Glasgow, Leicester, London) observational study involving infants ≤ 90 days, presenting to PED in the UK & Ireland with a fever ≥38°C between 31/08/2018 to 01/09/19.The aim was to report the performance of three CPGs; NICE Sepsis NG51, NCIE Feverish Illness NG143 and the proposed British Society Antimicrobial Chemotherapy (BSAC) guideline. The performance of clinician practice was also compared to the CPGs (i.e. what clinicians actually did). The primary outcome measure was the diagnosis of SBI defined as bacterial meningitis, Urinary Tract infection (UTI) or bacteraemia. The study was performed on behalf of PERUKI and registered with ClinicalTrials.gov Identifier: NCT04196192.

Results
535 febrile infants aged ≤90 days were included from the six centres. Median age of participants was 54 days with an Inter-quartile range (IQR) 32–70, 314 boys (58.7%) and 221 girls (41.3%). The median length of stay (LOS) of infants without SBI was 48 hours (IQR 25 to 69) and with SBI was 72 hours (IQR 48 to 116) with significant difference of p<0.0001.Sepsis NG51 correctly identified all 70 infants with SBI with a sensitivity of 1.00(95% CI 0.94 to 1.00). Clinician practice demonstrated the second highest sensitivity 0.97(95% CI 0.9 to 1.00) identifying 68 out of 70 SBI, followed by Fever NG143 -sensitivity 0.90 (95% CI 0.80 to 0.96). NICE sepsis was the most sensitive CPG and significantly more sensitive (McNemar’s Test) than NICE Feverish and BSAC (p<0.05) but not significantly more sensitive than clinician directed practice. Clinician directed practice was the most specific 0.29 (95%CI 0.25 to 0.33) and was significantly more specific than all CPGs (McNemar’s Test) p<0.0001.

Conclusions
Clinician directed practice was the most specific for identifying SBI with the fewest infants requiring parenteral antibiotics. The Clinician directed practice demonstrated a similar sensitivity as the most cautious NICE guidance (NG51 – treat all febrile infants) and was significantly more sensitive than the NICE NG143 and proposed BSAC CPGs. Further prospective studies are required to refine CPGs for the assessment and management of febrile infants in the UK and Ireland.