What is the recommended empiric treatment with ceftriaxone (Ceftriaxone IV) for a febrile infant less than 3 months old with diarrhea suspected of having a severe bacterial infection?

Ceftriaxone IV Dosing for Febrile Infants <3 Months with Diarrhea

For a febrile infant less than 3 months old with diarrhea suspected of having a severe bacterial infection, administer ceftriaxone 50 mg/kg IV or IM once daily as empiric therapy. 1

Age-Specific Dosing Recommendations

Infants 8-21 Days Old

• Do NOT use ceftriaxone monotherapy in this age group 1
• Administer ampicillin IV 150 mg/kg/day divided every 8 hours PLUS either:
  • Ceftazidime IV 150 mg/kg/day divided every 8 hours, OR
  • Gentamicin IV 4 mg/kg once daily 1
• The combination regimen is necessary to cover Group B Streptococcus and Listeria monocytogenes, which ceftriaxone alone does not adequately cover 1

Infants 22-28 Days Old

• Ceftriaxone IV or IM 50 mg/kg once daily is appropriate for suspected bacterial infection without identified focus 1
• For confirmed or suspected meningitis, use ampicillin IV 300 mg/kg/day divided every 6 hours PLUS ceftazidime IV 150 mg/kg/day divided every 8 hours 1

Infants 29 Days to 3 Months Old

• Ceftriaxone IV or IM 50 mg/kg once daily for suspected bacterial infection without identified focus 1
• For confirmed meningitis, increase dose to ceftriaxone IV 100 mg/kg/day (given once daily or divided every 12 hours) 1

Specific Indication: Bloody Diarrhea

The 2017 IDSA guidelines specifically recommend a third-generation cephalosporin (ceftriaxone) for infants <3 months of age with bloody diarrhea and suspected bacterial etiology. 1

• This recommendation applies when there is suspicion of invasive bacterial pathogens such as Shigella, Salmonella, or Campylobacter 1
• Ceftriaxone is preferred over fluoroquinolones due to increasing ciprofloxacin resistance in enteric pathogens 1
• The standard dose remains 50-80 mg/kg IV or IM once daily for 3 days for dysentery/invasive diarrhea 1

Critical Clinical Decision Points

When to Initiate Empiric Therapy

Administer parenteral antimicrobial therapy if ANY of the following apply: 1

• CSF analysis is abnormal (indicating meningitis)
• Urinalysis is abnormal (indicating UTI)
• Inflammatory markers are abnormal (indicating bacteremia risk >5%)
• Infant appears ill with fever, bloody diarrhea, and suspected bacterial etiology 1

Route of Administration

• IV or IM routes are equally effective for ceftriaxone 1
• IM administration allows for outpatient management in select cases where meningitis has been excluded 2
• Once-daily dosing provides convenience and maintains therapeutic levels for 24 hours 3

Important Caveats and Pitfalls

Bilirubin Concerns in Neonates

• Exercise caution with ceftriaxone in neonates with hyperbilirubinemia due to potential bilirubin displacement from albumin 4, 5
• Direct hyperbilirubinemia >2 mg/dL occurred in 2% of treated neonates in one study 5
• For infants 0-21 days old with jaundice, strongly consider the ampicillin-based regimen instead 1

Gallbladder Sludge

• Reversible gallbladder sludge (biliary pseudolithiasis) can occur with ceftriaxone use 5
• This typically resolves within 2 weeks after discontinuation and rarely causes clinical symptoms 5

STEC/Shiga Toxin-Producing E. coli

• AVOID antibiotics if STEC O157 or Shiga toxin 2-producing strains are suspected, as antibiotics may increase risk of hemolytic uremic syndrome (HUS) 1
• If bloody diarrhea is present without fever or systemic toxicity, consider STEC and withhold antibiotics pending stool culture results 1

Modify Therapy Based on Culture Results

• Narrow or discontinue antibiotics once culture results and sensitivities are available 1
• If no bacterial pathogen is identified and clinical improvement occurs, discontinue antibiotics 1

Monitoring and Follow-Up

• Reassess clinical status within 48-72 hours of initiating therapy 1
• If no improvement or worsening occurs, broaden coverage or investigate alternative diagnoses 1
• Monitor for adverse effects including rash, eosinophilia, thrombocytosis, and elevated alkaline phosphatase 5
• The overall cure rate for serious bacterial infections treated with ceftriaxone monotherapy is 94-97% 3