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]