Undifferentiated fever and fever without a source in infants and children — formative SAQs

1. Assessment and investigation plan (3 marks)

This is a febrile neonate (21 days, within the ≤28-day age band). Regardless of how well-appearing the infant is, the baseline SBI risk is 8-12% and clinical signs are unreliable. The infant requires a full septic workup and admission with empiric IV antibiotics. [6]

Investigations: [6] [13]

• Full blood count and differential — to assess white cell count and neutrophil/band counts
• Blood culture — obtained before antibiotic administration
• Urinalysis and urine culture — obtained by urethral catheterisation or suprapubic aspiration, not bag collection (contamination rate up to 30%)
• Lumbar puncture — CSF cell count, differential, protein, glucose, Gram stain and culture. Also send CSF for enterovirus PCR (season-dependent)
• CRP and procalcitonin — baseline inflammatory markers
• Chest radiograph — only if respiratory signs are present [6] [13]

Justification for admission: There is no low-risk pathway for neonates ≤28 days. The immune system is immature (neutrophil dysfunction, complement deficiency, maternal IgG nadir approaching at 3-12 weeks), clinical signs are blunted, and the risk of SBI including meningitis, bacteraemia and UTI is unacceptably high for outpatient management. [6]

2. Empiric antibiotic regimen (3 marks)

Cefotaxime 50 mg/kg per dose IV every 8-12 hours PLUS ampicillin 50 mg/kg per dose IV every 8 hours. [6] [13]

Rationale: [6] [13]

• Cefotaxime (not ceftriaxone) is used in neonates under 28 days because ceftriaxone displaces bilirubin from albumin, increasing the risk of kernicterus. Cefotaxime provides coverage for E. coli, Group B Streptococcus, and other Gram-negative organisms. [6]
• Ampicillin is added to cover Listeria monocytogenes, which third-generation cephalosporins do not reliably cover. Listeria is a recognised neonatal pathogen acquired from the maternal genital tract. [6]

3. Indications for adding aciclovir (2 marks)

Empiric aciclovir 20 mg/kg/dose IV every 8 hours should be added in any of the following situations: [6] [20]

• Seizure, focal neurological signs, or altered conscious state suggestive of HSV encephalitis
• Vesicular skin lesions or mucosal ulcers (though these may be absent)
• CSF pleocytosis with a negative Gram stain (raising the possibility of viral rather than bacterial meningitis, with HSV as the critical treatable differential) [6] [20]

Maternal history of genital HSV, particularly primary infection near delivery, is an additional indication. [6] [20]

4. Blood culture time-to-positivity (2 marks)

Biondi et al. demonstrated that the majority of positive blood cultures in febrile infants with true bacteraemia turn positive within 24 hours of collection. This supports the practice of observing for 24-48 hours before declaring a culture negative and discontinuing empiric antibiotics. If a culture turns positive after discharge (for infants managed as outpatients with a single dose of ceftriaxone), there must be a protocol for recall, re-evaluation and treatment. [6]

1. Clinical question and role of age (2 marks)

The clinical question is: does this infant have a serious bacterial infection (SBI) — specifically UTI, bacteraemia, or meningitis — that requires investigation and treatment, or is this a self-limiting viral illness? [1] [6]

Age is the primary risk stratifier. At 45 days, this infant falls in the 29-90 day age band, which carries a moderate SBI risk of approximately 3-8%. This is substantially higher than the risk in older children, but unlike the neonatal age band, there are validated prediction rules that can identify a low-risk subgroup. The infant is therefore evaluated using a prediction rule (PECARN, Rochester or Boston per local protocol) rather than the mandatory full-workup approach required for neonates. [1] [6]

2. Investigations and urine collection (3 marks)

Investigations: [1] [6]

• Urinalysis and urine culture — mandatory for all febrile infants in this age group (UTI is the most common SBI)
• Full blood count with differential — ANC and total WCC
• CRP and procalcitonin — to apply the PECARN rule (PCT ≥1.7 ng/mL and CRP ≥20 mg/L are high-risk thresholds)
• Blood culture — drawn before any antibiotics
• Lumbar puncture — indicated if the infant is ill-appearing, if biomarkers are abnormal, or if the prediction rule does not classify the infant as low-risk [1] [6]

Urine collection method: Urine must be obtained by urethral catheterisation or suprapubic aspiration (SPA), not bag collection. Bag specimens have contamination rates of up to 30% due to perineal and skin flora contamination, leading to unacceptable false-positive rates. A positive bag culture must always be confirmed with a catheter or SPA specimen before a UTI diagnosis is committed to. [6] [13]

3. Comparison of prediction rules (3 marks)

The key difference is that PECARN incorporates procalcitonin (and a urinary biomarker, uNGAL), which gives it superior discrimination compared to the older rules that rely only on white cell count and band count. The Rochester criteria are the simplest and do not require LP for their low-risk definition. The Boston criteria are the most conservative — they include LP, give empiric ceftriaxone, and mandate 24-hour review. [1] [2] [3]

4. Safe discharge and safety-net (2 marks)

If investigations are reassuring (infant meets low-risk criteria, urinalysis is negative, biomarkers are within low-risk thresholds, blood culture is pending but the infant is well-appearing), the criteria for safe discharge are: [6] [13]

• The infant remains well-appearing at the time of discharge
• The caregiver understands the safety-net and can return promptly if symptoms worsen
• Follow-up is arranged within 24 hours
• A protocol exists for recalling the family if the blood culture turns positive [6] [13]

Safety-net content: The safety-net must be specific, written and actionable: "Return immediately to the emergency department if the infant develops [any of: persistent or increasing fever, irritability or lethargy, poor feeding, vomiting, rash, breathing difficulty, reduced wet nappies, or if you are worried the infant is not right]." [6] [13]