Identifying febrile infants with serious and invasive bacterial infections (SBI/IBI) is a daily challenge on the emergency department (ED) shopfloor. International clinical practice guidelines (CPGs) attempt to stratify high and low-risk infants to select those who may benefit from invasive testing and treatment. However, the use of procalcitonin testing excludes them from day-to-day practice in the UK and Ireland. Routine assessment, testing and gut-feeling can get us so far; but, could local CPGs for the management of febrile infants help us to direct care for this age group?
Waterfield T, Lyttle MD, Munday C, et al on behalf of PERUKI. Validating clinical practice guidelines for the management of febrile infants presenting to the emergency department in the UK and Ireland. ADC Published Online First: 16 September 2021. doi: 10.1136/archdischild-2021-322586
Why is this study needed?
Febrile infants, particularly those ≤90 days, are at high risk of serious and invasive bacterial infections. 10-20% have bacteraemia, meningitis or a urinary tract infection. There is, however, no single test that can confirm the presence of an SBI/IBI. Clinicians have consequently adopted a cautious approach. This leads to blood tests, lumbar punctures, administration of intravenous antibiotics and admission.
Is there a validated approach to management the febrile infant?
Internationally, there are a number of validated approaches, including Pediatric Emergency Care Applied Research Network (PECARN) and Step-By-Step clinical practice guidelines. However, they have not translated to the UK and Irish setting due to their reliance on the use of serum procalcitonin testing which is not widely available here.
In the UK and Ireland, there are three main Clinical Practice Guidelines used to assist with recognition and management of this presentation without the use of procalcitonin testing, however, they have not yet been validated.
NICE Sepsis: recognition, diagnosis and early management (NICE NG51): all febrile infants <3 months should be treated for suspected sepsis irrespective of their clinical appearance and laboratory test results.
NICE Fever in under 5s: assessment and initial management (NICE NG143): all febrile infants <1 month, all febrile infants 1-3 months who appear unwell and all febrile infants 1-3 months with WCC less than 5×109/L or greater than 15×109/L should receive parenteral antibiotic therapy.
British Society for Antimicrobial Chemotherapy (BASC): all febrile infants <1 month, all febrile infants 1–3 months who appear unwell and all febrile infants with positive urinalysis or C-reactive protein (CRP) >20 mg/L should receive parenteral antibiotic therapy.
How did the team approach the study?
This study aimed to report rates of SBI/IBI among febrile infants <90 days of age presenting to UK and Irish hospitals, to validate CPGs in use in this setting and to describe predictors of SBI/IBI. The design was of a retrospective cohort study conducted in six UK and Irish tertiary paediatric EDs in the PERUKI network (one in Northern Ireland; one in Scotland; three in England; one in the Republic of Ireland).
This study included febrile infants with a recorded fever of ≥38°C at triage) aged 90 days or younger attending between 31 August 2018 and 1 September 2019 (screened for inclusion by searching emergency clinical software databases). There were no exclusion criteria.
What were they looking for?
Primary Outcomes. There were two primary outcomes: performance accuracy (sensitivity, specificity) of the three CPGs in identifying infants with SBI/IBI and performance accuracy of clinicians in identifying infants with SBI/IBI. Secondary Outcomes: rates and types of SBI/IBI; LOS; procedures performed; use of antimicrobial drugs; clinical predictors of SBI/IBI.
What did they find?
555 infants were included in the analysis. The median age was 53 days (IQR 32 to 70). 447 (81%) underwent blood testing, 90% were admitted and 421 (76%) received parenteral antibiotics. This was all despite only 14% being confirmed as having an SBI/IBI. There were five participants with bacterial meningitis (1%), seven with bacteraemia (1%) and 66 (12%) with urinary tract infections. None of the studied CPGs showed ideal performance characteristics.
Sensitivity* of CPGs
* the proportion of those with the condition who are correctly identified by the test (or, in this case, guideline).
The NICE Sepsis CPG had the highest sensitivity at 1.00 (95% CI 0.95 to 1.00, p=0.25), followed by NICE Fever Under 5 at 0.91 (95% CI 0.82 to 0.96, p=0.0233)and then BSAC at 0.82 (95% 0.72 to 0.90, p=0.0005)
Specificity* of CPGs
*the proportion of those without the condition who are correctly identified by the test (or guideline)
Despite (or, more likely, because) NICE Sepsis was highly sensitive, it was the least specific at 0.0 (95% CI 0.0 to 0.01), followed by NICE Fever Under 5 at 0.09 (95% CI 0.07 to 0.12, p<0.0001). BSAC had the highest specificity of 0.14 (95% CI 0.1 to 0.17, p<0.0001).
Accuracy of Clinician Practice
Clinicians had a high sensitivity of 0.96 (95% CI 0.89 to 0.99) with a specificity of 0.27 (95% CI 0.24 to 0.32).
While sensitivity showed no significant difference to the best performing CPG (p=0.25), the specificity was significantly higher than that seen for all CPGs (p<0.0001). The study team suggested that clinicians may have been combining clinical experience with the general principles outlined in the CPGs studied, meaning they were more accurate than any CPG in isolation.
CASP Checklist for Cohort Studies
What does it mean for current practice?
None of the CPGs studied performed well enough to radically alter current practice. While safe, the most sensitive, NICE Sepsis, requires that all infants receive parenteral antibiotic therapy. This perpetuates the cautious approach already adopted by clinicians. A more tailored approach, as in NICE Fever Under 5 and BSAC, may be more favourable in avoiding invasive testing and treatment. However, due to a reduced specificity (i.e. failure to recognise a febrile infant with an SBI/IBI) treating an infant according to these CPGs requires monitoring and follow-up (as an in-patient or in the community). Is this something that we have the capacity to do? Or, should we find capacity to do, in order to avoid invasive testing and treatment of well children?
Thoughts from the author – Tom Waterfield
Whilst all observation retrospective research is limited by potentially missed cases and recall bias, this study reassuringly reports similar findings to larger prospective international studies from the USA and Europe.
In the post-vaccine era, bacterial meningitis and septicaemia are exceptionally rare in well-appearing infants over one month of age with normal urinalysis and a CRP <20mg/l. This specific group are unlikely to benefit from a lumbar puncture or parenteral antibiotics. In this lower risk cohort, some infants will have a positive urine culture at 24 to 36 hours. This may represent an evolving urinary tract infection or a contaminant. Any institution considering a tailored approach to treatment needs to consider how they would manage a positive urine result at 24 to 36 hours in an infant who has been discharged without treatment.
The recently published American Academy of Pediatrics guidance considers this in more detail.
