What is the recommended empiric antibiotic regimen, adjunctive dexamethasone use, and treatment duration for acute bacterial meningitis in neonates, children, and adults?

Bacterial Meningitis Treatment

Initiate empiric antibiotics within 1 hour of presentation—do not delay for lumbar puncture or imaging—and tailor therapy by age and risk factors, adding adjunctive dexamethasone with or before the first antibiotic dose to reduce mortality and neurological sequelae.

Critical Timing Principles

• Antibiotic administration must occur within 60 minutes of hospital arrival, as delays are strongly associated with increased mortality and poor neurological outcomes 1, 2.
• Start antibiotics immediately upon clinical suspicion—do not wait for lumbar puncture, CSF results, or CT imaging 3, 1.
• Obtain blood cultures before antibiotics, but never delay treatment beyond 1 hour to obtain them 1, 2.
• If lumbar puncture is postponed (e.g., for CT in patients with focal deficits, new seizures, or altered mental status), begin empiric therapy without delay 3, 4.

Empiric Antibiotic Regimens by Age and Risk Factors

Neonates (<1 Month)

• Age <1 week: Ampicillin 50 mg/kg IV every 8 hours plus cefotaxime 50 mg/kg IV every 8 hours plus gentamicin 2.5 mg/kg IV every 12 hours 3, 1.
• Age 1–4 weeks: Ampicillin 50 mg/kg IV every 6 hours plus cefotaxime 50 mg/kg IV every 6–8 hours plus gentamicin 2.5 mg/kg IV every 8 hours 3, 1.
• Rationale: Neonatal meningitis is commonly caused by Group B Streptococcus, Escherichia coli, and Listeria monocytogenes, requiring ampicillin for Listeria coverage and an aminoglycoside for gram-negative organisms 1, 5.

Children (1 Month to 18 Years)

• Ceftriaxone 50 mg/kg IV every 12 hours (maximum 2 g per dose) or cefotaxime 75 mg/kg IV every 6–8 hours plus vancomycin 10–15 mg/kg IV every 6 hours (target trough 15–20 μg/mL) 3.
• Alternative: Rifampicin 10 mg/kg every 12 hours (up to 600 mg/day) may replace vancomycin in regions where pneumococcal resistance to third-generation cephalosporins is uncommon 3.
• Rationale: This regimen covers Streptococcus pneumoniae (including penicillin- and cephalosporin-resistant strains), Neisseria meningitidis, and Haemophilus influenzae 2, 6.

Adults 18–50 Years (Immunocompetent)

• Ceftriaxone 2 g IV every 12 hours (or 4 g IV once daily) or cefotaxime 2 g IV every 4–6 hours plus vancomycin 10–20 mg/kg IV every 8–12 hours (target trough 15–20 μg/mL) 3, 1.
• Alternative: Rifampicin 300 mg IV every 12 hours may be used instead of vancomycin 3.
• Rationale: This combination provides coverage for S. pneumoniae (including resistant strains) and N. meningitidis, the most common pathogens in this age group 1, 2.

Adults >50 Years or Immunocompromised (Any Age)

• Ceftriaxone 2 g IV every 12 hours (or 4 g IV once daily) or cefotaxime 2 g IV every 4–6 hours plus vancomycin 10–20 mg/kg IV every 8–12 hours plus ampicillin 2 g IV every 4 hours (or amoxicillin 2 g IV every 4 hours) 3, 1.
• Risk factors for Listeria include age >50 years, diabetes mellitus, immunosuppressive drugs, cancer, and other immunocompromising conditions 3, 2.
• Rationale: Listeria monocytogenes is a significant pathogen in older and immunocompromised patients, and cephalosporins lack activity against Listeria—ampicillin or amoxicillin is essential 3, 1, 2.

Adjunctive Dexamethasone Therapy

• Administer dexamethasone 0.15 mg/kg IV every 6 hours for 2–4 days (adults: 10 mg IV every 6 hours for 4 days) with or within 10–15 minutes before the first antibiotic dose 3, 4, 7, 8.
• Dexamethasone is unequivocally recommended for children and adults with suspected or proven pneumococcal or Haemophilus influenzae meningitis, as it reduces mortality and neurological sequelae (especially hearing loss) 3, 7, 8.
• Do not use dexamethasone for meningococcal septicemia unless inotrope-resistant shock develops 4.
• Evidence: A 2-day regimen appears as effective as a 4-day regimen for H. influenzae and meningococcal meningitis, with similar rates of sequelae 9, 7.

Pathogen-Specific Treatment (After Identification)

Streptococcus pneumoniae

• Penicillin-sensitive (MIC <0.1 mg/mL): Penicillin G or ampicillin; alternative: third-generation cephalosporin 3.
• Penicillin-intermediate (MIC 0.1–1.0 mg/mL): Third-generation cephalosporin (ceftriaxone or cefotaxime); alternative: cefepime or meropenem 3.
• Penicillin-resistant (MIC ≥2.0 mg/mL) or cephalosporin-resistant (MIC ≥1.0 mg/mL): Vancomycin plus third-generation cephalosporin; alternative: fluoroquinolone (e.g., moxifloxacin) 3, 1.
• Duration: 10–14 days 1, 2.

Neisseria meningitidis

• Penicillin-sensitive (MIC <0.1 mg/mL): Penicillin G or ampicillin; alternative: third-generation cephalosporin 3.
• Penicillin-intermediate (MIC 0.1–1.0 mg/mL): Third-generation cephalosporin (ceftriaxone or cefotaxime) 3.
• Duration: 5–7 days 1, 2.
• Eradication: Single dose of ciprofloxacin 500 mg PO for nasopharyngeal carriage 2.

Listeria monocytogenes

• Ampicillin 2 g IV every 4 hours or penicillin G; alternative: trimethoprim-sulfamethoxazole or meropenem 3, 1.
• Duration: 21 days 1, 6.
• Note: Gentamicin may be added for synergy in severe cases 6.

Haemophilus influenzae

• Ceftriaxone 2 g IV every 12 hours or cefotaxime 2 g IV every 6 hours 1.
• Duration: 10 days 1, 6.

Gram-Negative Bacilli (e.g., E. coli, Klebsiella)

• Third-generation cephalosporin (ceftriaxone or cefotaxime); alternatives: aztreonam, fluoroquinolone, meropenem, or trimethoprim-sulfamethoxazole 3.
• Aminoglycosides (gentamicin, tobramycin, or amikacin) should be added, especially in neonates 3, 6.
• Duration: 14–21 days 4.

Regional Resistance Considerations

• In regions with high pneumococcal penicillin or cephalosporin resistance, add vancomycin or rifampicin to the third-generation cephalosporin empirically 3, 1.
• When true resistance to third-generation cephalosporins (MIC >2 mg/L) is unlikely, some experts suggest ceftriaxone or cefotaxime alone, but adding vancomycin is recommended as a safety measure 3.
• Animal studies (no clinical trials available) show that ceftriaxone combined with vancomycin or rifampicin achieves higher CSF sterilization rates than ceftriaxone alone in resistant pneumococcal meningitis 3.

Common Pitfalls to Avoid

• Do not delay antibiotics for imaging: If CT is indicated (focal deficits, new seizures, GCS <10, severe immunocompromise), administer antibiotics first, then obtain imaging 1, 2, 4.
• Do not omit ampicillin in patients >50 years or immunocompromised: Cephalosporins lack activity against Listeria, and failure to cover this pathogen can be fatal 3, 1, 2.
• Do not underdose antibiotics: Meningitis requires high-dose therapy to achieve adequate CSF penetration—standard dosing may lead to treatment failure 1, 2.
• Do not neglect blood cultures: Obtain them before antibiotics, but never delay treatment beyond 1 hour to obtain them 1, 2.
• Do not stop antibiotics prematurely based on clinical improvement: Complete the pathogen-specific duration to prevent relapse and complications 2.

Treatment Duration Summary

• Meningococcal meningitis: 5–7 days 1, 2.
• Pneumococcal meningitis: 10–14 days 1, 2.
• Haemophilus influenzae meningitis: 10 days 1, 6.
• Listeria meningitis: 21 days 1, 6.
• Gram-negative meningitis: 14–21 days 4.
• Culture-negative meningitis with clinical recovery: 10 days 2.

Outpatient Parenteral Antibiotic Therapy (OPAT)

• Consider OPAT if the patient is afebrile, clinically improving, has received at least 5 days of inpatient therapy, has reliable IV access, can access medical care 24 hours per day, and is willing to participate 1, 2.
• Appropriate OPAT regimen: Ceftriaxone 2 g IV twice daily (or 4 g IV once daily after the first 24 hours) 1, 2.