Is ceftriaxone (a broad-spectrum cephalosporin antibiotic) 2g intravenous (IV) twice daily (bid) an appropriate treatment for a brain infection caused by Cutibacterium acnes that is sensitive to penicillin?

Ceftriaxone 2g IV BID is NOT the Optimal Treatment for Penicillin-Sensitive Cutibacterium acnes Brain Infection

For penicillin-sensitive Cutibacterium acnes brain infections, high-dose intravenous penicillin G (20-24 million units daily in divided doses) is the preferred first-line treatment, not ceftriaxone. 1, 2, 3

Guideline-Based Treatment Recommendations

First-Line Therapy

• Penicillin G 20 million units IV every 24 hours (continuous infusion or divided into 6 doses) is the preferred treatment for Cutibacterium acnes CNS infections 1
• Alternative regimen: Ceftriaxone 2g IV every 24 hours (once daily, not twice daily) is listed as an acceptable alternative, but NOT as first-line therapy 1
• Treatment duration: 4-6 weeks of intravenous therapy 1

Alternative Agents (If Penicillin Cannot Be Used)

• Clindamycin 600-900 mg IV every 8 hours or 300-450 mg PO four times daily 1
• Vancomycin 15 mg/kg IV every 12 hours 1

Why Ceftriaxone 2g BID is Inappropriate

Dosing Frequency Error

• Ceftriaxone for C. acnes is dosed once daily (2g every 24 hours), not twice daily 1
• The twice-daily dosing (2g every 12 hours) is reserved for bacterial meningitis caused by organisms like Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae 1, 4, 5, 6
• C. acnes does not require the aggressive twice-daily dosing needed for rapidly dividing pyogenic bacteria 1

Suboptimal Antimicrobial Choice

• Penicillin G demonstrates superior clinical outcomes for C. acnes CNS infections with minimal inhibitory concentrations (MICs) ranging from 0.03-0.12 mg/L 2
• Historical case series show excellent cure rates with high-dose penicillin (3-4 million units IV every 4 hours) combined with surgical drainage 2, 3
• C. acnes is an indolent, slow-growing anaerobe that responds best to beta-lactams with narrow spectrum activity 2, 3, 7

Clinical Algorithm for C. acnes Brain Infection

Step 1: Confirm Diagnosis

• Obtain anaerobic cultures from surgical specimens (C. acnes is frequently missed on routine aerobic cultures) 8, 7
• Look for Gram-positive bacilli on Gram stain—this should NOT be dismissed as contamination in neurosurgical specimens 7
• Expect indolent presentation with delayed onset (median 54 days post-surgery, range 12-1,578 days) 7

Step 2: Surgical Management

• Remove all foreign bodies (shunts, bone flaps, prosthetic devices) 2, 3, 7
• Perform surgical drainage of purulent collections (abscesses, subdural empyemas) 2, 3
• C. acnes produces biofilm on prosthetic devices, making medical therapy alone insufficient 8

Step 3: Antimicrobial Therapy

• If penicillin-sensitive: Penicillin G 20-24 million units IV daily (divided every 4 hours or continuous infusion) 1, 2, 3
• If penicillin allergy or intolerance: Ceftriaxone 2g IV once daily (every 24 hours) 1
• Duration: 4-6 weeks of intravenous therapy 1, 3
• For extracranial bone-flap infections: Consider shorter courses (≤7 days IV) after hardware removal 7

Step 4: Monitoring

• Serial imaging to confirm resolution of infectious collections 3
• Monitor for relapse or reinfection (occurs in approximately 7% of cases) 7
• No adverse reactions to high-dose penicillin were reported in published case series 2

Common Pitfalls to Avoid

• Do not dismiss Gram-positive bacilli on Gram stain as contaminants—this is often C. acnes in neurosurgical specimens 7
• Do not rely solely on routine aerobic cultures—obtain anaerobic cultures for all CNS infections with foreign bodies 8, 7
• Do not use ceftriaxone twice daily dosing—this wastes resources and provides no additional benefit for C. acnes 1
• Do not attempt medical therapy alone without removing infected hardware—biofilm production makes this approach futile 8
• Do not use short treatment courses—intracranial C. acnes infections require 4-6 weeks of IV therapy 1, 3

Special Populations

Immunosuppressed Patients

• Higher susceptibility to C. acnes CNS infections despite the organism's typically benign nature 3
• Maintain same treatment principles: surgical drainage + prolonged IV penicillin 3

Prosthetic Joint Infection Guidelines (Extrapolated)

• The IDSA prosthetic joint infection guidelines also recommend penicillin G as first-line for C. acnes, with ceftriaxone 2g once daily as an alternative 1
• This reinforces the principle that penicillin remains superior for penicillin-sensitive C. acnes regardless of infection site 1