Is a single dose of ceftriaxone (Ceftriaxone) recommended for traumatic brain injury (TBI) without evidence of infection?

Single Dose Ceftriaxone in TBI: Not Recommended for Routine Prophylaxis

A single dose of ceftriaxone is not recommended for traumatic brain injury without evidence of infection, except in the specific context of preventing early ventilator-associated pneumonia in mechanically ventilated patients with severe brain injury.

Evidence-Based Recommendation

The available evidence does not support routine antibiotic prophylaxis for TBI patients without infection. However, a recent high-quality randomized controlled trial demonstrates benefit in a specific subpopulation:

When Single-Dose Ceftriaxone IS Indicated

• For mechanically ventilated patients with severe brain injury (GCS ≤12), a single 2g IV dose of ceftriaxone within 12 hours of intubation significantly reduces early ventilator-associated pneumonia (14% vs 32%, p=0.030) without microbiological resistance or adverse effects 1
• This intervention specifically prevents VAP occurring between days 2-7 of mechanical ventilation in comatose brain injury patients 1

When Single-Dose Ceftriaxone is NOT Indicated

• For closed head injury without mechanical ventilation, there is no evidence supporting prophylactic antibiotics 2
• For ICP monitor placement, broad-spectrum prophylaxis including ceftriaxone does not reduce CNS infections (1.7% with narrow-spectrum vs 4.4% with ceftriaxone, p=NS) but increases acquisition of resistant gram-negative pathogens 3
• For penetrating TBI, while institutional data suggested potential benefit, systematic review of 327 cases showed no significant reduction in CNS infection (17% with antibiotics vs 19% without, p=0.76) 4

Clinical Algorithm for Decision-Making

Step 1: Assess for active infection

• If CSF leak, open skull fracture, or contaminated wound present → treat as active infection with appropriate multi-day regimen, not single-dose prophylaxis 5

Step 2: Determine ventilation status

• If requiring mechanical ventilation for ≥48 hours AND GCS ≤12 → Give single 2g IV ceftriaxone within 12 hours of intubation 1
• If not mechanically ventilated → No prophylactic antibiotics indicated 2

Step 3: Monitor for infection development

• Frequent cultures when infection suspected rather than empiric antibiotics 2
• Maintain high index of suspicion for catheter-related infections 2

Critical Pitfalls to Avoid

• Do not use broad-spectrum prophylaxis for ICP monitors - it shifts flora toward resistant gram-negative organisms without reducing infection rates 3
• Do not continue antibiotics beyond single dose in ventilated patients without documented infection - the benefit is specific to early VAP prevention, not treatment 1
• Do not withhold the single dose in appropriate candidates (mechanically ventilated, GCS ≤12) - this represents Level 1 evidence for harm reduction 1
• Do not use prophylactic antibiotics to mask inadequate infection surveillance - appropriate cultures and monitoring remain essential 2

Strength of Evidence

The recommendation against routine prophylaxis is based on multiple studies showing no benefit and potential harm from resistance 4, 2, 3. The single exception for ventilated patients comes from a 2024 multicenter randomized controlled trial (PROPHY-VAP) representing the highest quality evidence available 1. This trial specifically excluded patients receiving selective digestive decontamination and used masked outcome assessment, strengthening its validity 1.