What empiric antibiotics and dosing should be used for acute bacterial meningitis in adults, children, and neonates, including adjunctive dexamethasone and alternatives for severe β‑lactam allergy?

Empiric Antibiotic Therapy for Acute Bacterial Meningitis

Administer empiric antibiotics within 60 minutes of hospital arrival—delays beyond this window significantly increase mortality and neurological sequelae. 1

Critical Timing Principles

• Start antibiotics immediately upon clinical suspicion without waiting for lumbar puncture, cerebrospinal fluid results, or imaging. 2, 1
• Obtain blood cultures before the first antibiotic dose, but never delay treatment to obtain them. 1, 3
• If lumbar puncture is postponed for CT imaging (focal deficits, new seizures, GCS <10, severe immunocompromise), give antibiotics first, then image. 1, 3

Empiric Regimens by Age and Risk Category

Neonates (≤4 weeks)

Age <1 week:

• Ampicillin 50 mg/kg IV q8h + Cefotaxime 50 mg/kg IV q8h + Gentamicin 2.5 mg/kg IV q12h 2, 1
• Alternative aminoglycosides: Tobramycin 2.5 mg/kg IV q8h or Amikacin 10 mg/kg IV q8h 2

Age 1–4 weeks:

• Ampicillin 50 mg/kg IV q6h + Cefotaxime 50 mg/kg IV q6–8h + Gentamicin 2.5 mg/kg IV q8h 2, 1

Rationale: This combination covers Group B Streptococcus, Escherichia coli, and Listeria monocytogenes—the dominant neonatal pathogens. 1

Children (1 month–18 years)

• Ceftriaxone 50 mg/kg IV q12h (max 2 g/dose) OR Cefotaxime 75 mg/kg IV q6–8h 2, 1
• PLUS Vancomycin 10–15 mg/kg IV q6h (target trough 15–20 µg/mL) 2, 1
• Alternative to vancomycin in low-resistance regions: Rifampicin 10 mg/kg IV q12h (max 600 mg/day) 2, 1

Rationale: Ensures coverage of Streptococcus pneumoniae (including resistant strains), Neisseria meningitidis, and Haemophilus influenzae. 1

Adults 18–50 Years (Immunocompetent)

• Ceftriaxone 2 g IV q12h (or 4 g IV q24h) OR Cefotaxime 2 g IV q4–6h 2, 1
• PLUS Vancomycin 10–20 mg/kg IV q8–12h (target trough 15–20 µg/mL) 2, 1
• Alternative to vancomycin in low-resistance settings: Rifampicin 300 mg IV q12h 2, 1

Rationale: Covers S. pneumoniae (including resistant strains) and N. meningitidis, the most common adult pathogens. 1

Adults >50 Years OR Immunocompromised (Any Age)

• Ceftriaxone 2 g IV q12h (or 4 g IV q24h) OR Cefotaxime 2 g IV q4–6h 2, 1
• PLUS Vancomycin 10–20 mg/kg IV q8–12h (target trough 15–20 µg/mL) 2, 1
• PLUS Ampicillin 2 g IV q4h (or Amoxicillin 2 g IV q4h) 2, 1

Rationale: Ampicillin is essential for Listeria monocytogenes coverage, as cephalosporins lack activity against this pathogen. 1

Listeria risk factors include: age >50 years, diabetes mellitus, immunosuppressive therapy, malignancy, and other immunocompromising conditions. 2, 1

Adjunctive Dexamethasone

Adults:

• Dexamethasone 10 mg IV q6h for 4 days 1, 4
• Give with or 10–20 minutes before the first antibiotic dose 1, 4

Children:

• Dexamethasone 0.15 mg/kg IV q6h for 2–4 days 1, 3
• Administer with or within 24 hours of the first antibiotic dose 3

Indications: Strongly recommended for suspected or proven S. pneumoniae or H. influenzae meningitis—reduces mortality and hearing loss. 1, 5, 4

Critical caveat: Discontinue dexamethasone if Listeria is identified, as steroids increase mortality in neurolisteriosis. 1

Pathogen-Specific Therapy After Identification

Pathogen	Susceptibility	Definitive Therapy	Duration
S. pneumoniae	Penicillin-sensitive (MIC <0.1 mg/L)	Penicillin G 2.4 g IV q4h OR continue ceftriaxone/cefotaxime [1]	10–14 days [1]
S. pneumoniae	Penicillin-resistant (MIC ≥2 mg/L) OR cephalosporin-resistant	Vancomycin + ceftriaxone/cefotaxime [1]	10–14 days [1]
N. meningitidis	Penicillin-sensitive	Penicillin G 2.4 g IV q4h OR ceftriaxone 2 g IV q12h [1]	5–7 days [1]
L. monocytogenes	—	Ampicillin 2 g IV q4h [1]	21 days [1]
H. influenzae	—	Ceftriaxone 2 g IV q12h OR cefotaxime 2 g IV q6h [1]	10 days [1]

Regional Resistance Considerations

• In areas with high pneumococcal penicillin or cephalosporin resistance, add vancomycin or rifampicin to the third-generation cephalosporin. 2, 1
• When true cephalosporin resistance (MIC >2 mg/L) is unlikely, some experts suggest ceftriaxone/cefotaxime alone, but adding vancomycin is recommended as a safety measure. 2, 1
• Animal studies demonstrate that ceftriaxone combined with vancomycin or rifampicin achieves higher cerebrospinal fluid sterilization rates than ceftriaxone alone in resistant pneumococcal meningitis. 2

Severe β-Lactam Allergy Alternatives

For adults with severe β-lactam allergy:

• Vancomycin 10–20 mg/kg IV q8–12h (target trough 15–20 µg/mL) PLUS Moxifloxacin 400 mg IV q24h for pneumococcal coverage 1
• PLUS Trimethoprim-sulfamethoxazole 5 mg/kg (TMP component) IV q6–8h for Listeria coverage in patients >50 years or immunocompromised 1

For children with severe β-lactam allergy:

• Vancomycin 10–15 mg/kg IV q6h PLUS Rifampicin 10 mg/kg IV q12h (max 600 mg/day) 2, 1

Critical Pitfalls to Avoid

• Never delay antibiotics for imaging—give antibiotics first, then obtain CT if indicated. 1, 3
• Never omit ampicillin in patients >50 years or immunocompromised; omission can result in fatal Listeria infection. 1
• Never underdose—meningitis requires high-dose regimens to achieve adequate cerebrospinal fluid penetration. 1
• Never fail to obtain blood cultures before antibiotics, but do not let this delay treatment beyond 60 minutes. 1, 3
• Never ignore local resistance patterns—adjust empiric therapy based on regional antimicrobial susceptibility data. 1
• Never continue dexamethasone if Listeria is identified—steroids worsen outcomes in neurolisteriosis. 1