What is the appropriate empiric antibiotic regimen for a 78‑year‑old man presenting with fever and altered consciousness whose cerebrospinal fluid Gram stain shows gram‑positive bacilli that are catalase‑positive (suggesting Listeria monocytogenes)?

Treatment of Listeria Meningitis in a 78-Year-Old Male

The correct answer is B: Ceftriaxone + Ampicillin + Vancomycin. This 78-year-old patient with CSF showing gram-positive bacilli that are catalase-positive has Listeria monocytogenes meningitis, which requires ampicillin as the cornerstone of therapy, but empiric coverage must also address Streptococcus pneumoniae (including resistant strains) until cultures definitively exclude it.

Why Ampicillin Must Be Included

• Listeria monocytogenes is naturally resistant to all cephalosporins, including ceftriaxone and cefotaxime, making cephalosporin monotherapy completely ineffective 1
• High-dose intravenous ampicillin 2 g every 4 hours is the definitive treatment for all forms of listeriosis, including CNS infections 1, 2
• The FDA label explicitly indicates ampicillin for bacterial meningitis caused by Listeria monocytogenes 3
• Gentamicin should be added to ampicillin for synergistic bactericidal activity, which is particularly critical in meningitis and CNS infections 1

Why Ceftriaxone + Vancomycin Are Also Required Initially

• Age >50 years is a major risk factor for Listeria, but Streptococcus pneumoniae remains the most common cause of bacterial meningitis in adults (72% of cases) 4, 5
• Until culture results definitively identify the organism, empiric therapy must cover both pneumococcus (including resistant strains) and Listeria 5
• Ceftriaxone 2 g IV every 12 hours plus vancomycin 15-20 mg/kg IV every 8-12 hours is the standard empiric regimen for adults, with ampicillin added for patients ≥60 years or immunocompromised 5, 1
• The UK Joint Specialist Societies guideline confirms this approach: for adults >60 years with suspected meningitis, empiric therapy includes ceftriaxone/cefotaxime PLUS vancomycin (for resistant pneumococcus) PLUS ampicillin (for Listeria) 2

Treatment Duration and Adjunctive Therapy

• Listeria meningitis requires 21 days of intravenous therapy 2, 1
• Dexamethasone should be discontinued immediately once Listeria is identified or suspected, as it may worsen outcomes in listeriosis 1, 4
• Gentamicin 4 mg/kg IV once daily should be added to ampicillin for synergistic bactericidal activity 1

Why the Other Options Are Incorrect

• Option A (Ceftriaxone + Vancomycin + Steroid): Lacks ampicillin, which is absolutely essential for Listeria. Steroids should be stopped once Listeria is identified 1, 4
• Option C (Ceftriaxone + Vancomycin + Ampicillin): This is actually the same as option B, just written in different order—both are correct
• Option D (Ampicillin alone): While ampicillin is essential for Listeria, monotherapy is inadequate until pneumococcal meningitis is definitively excluded by culture. Empiric coverage must address both pathogens 5, 4

Critical Clinical Pitfalls to Avoid

• Never use cephalosporin monotherapy for suspected or confirmed Listeria infection—it will fail completely 1
• Do not delay ampicillin in high-risk populations (age >50, immunocompromised, diabetes, chronic liver disease, pregnancy) with suspected meningitis 1, 5
• Gram stain sensitivity for Listeria is only 33%, so a negative Gram stain does not exclude Listeria in high-risk patients 5
• Fluoroquinolones should be avoided as they are not reliably active against Listeria monocytogenes 1

Definitive Therapy Once Listeria Is Confirmed

Once cultures confirm Listeria monocytogenes, the regimen should be streamlined to:

• Ampicillin 2 g IV every 4 hours PLUS gentamicin for 21 days 1, 2
• Alternative for penicillin allergy: Co-trimoxazole 10-20 mg/kg/day (trimethoprim component) divided into 4 doses 1, 2
• Vancomycin and ceftriaxone can be discontinued once pneumococcal meningitis is excluded 2