What empiric intravenous antibiotics, dosing, duration, and adjunctive dexamethasone should be given to an adult with suspected acute bacterial meningoencephalitis, and how should the regimen be modified for severe beta‑lactam or penicillin allergy?

Empiric Antibiotic Management for Acute Bacterial Meningoencephalitis

Initiate ceftriaxone 2g IV every 12 hours (or cefotaxime 2g IV every 4–6 hours) plus vancomycin 15–20 mg/kg IV every 8–12 hours within 1 hour of presentation, and add ampicillin 2g IV every 4 hours if the patient is ≥50 years old or immunocompromised. 1, 2, 3

Critical Timing Principles

• Administer antibiotics within 60 minutes of hospital arrival—delays beyond this window directly correlate with increased mortality and worse neurological outcomes. 1, 2, 3
• Start empiric therapy immediately on clinical suspicion, without waiting for lumbar puncture, CSF results, or imaging. 4, 1, 2
• Obtain blood cultures before the first antibiotic dose, but never postpone treatment beyond 1 hour to acquire them. 1, 2, 3
• If lumbar puncture is delayed for CT imaging (due to focal deficits, new seizures, altered consciousness, or immunocompromise), give antibiotics first, then obtain imaging. 4, 1, 2

Empiric Antibiotic Regimens by Age and Risk Factors

Adults 18–50 Years (Immunocompetent)

• Ceftriaxone 2g IV every 12 hours (or cefotaxime 2g IV every 4–6 hours) PLUS vancomycin 15–20 mg/kg IV every 8–12 hours (target trough 15–20 µg/mL). 4, 1, 3
• This combination covers Streptococcus pneumoniae (including resistant strains), Neisseria meningitidis, and Haemophilus influenzae. 1, 2, 3

Adults ≥50 Years or Immunocompromised (Any Age)

• Ceftriaxone 2g IV every 12 hours (or cefotaxime 2g IV every 4–6 hours) PLUS vancomycin 15–20 mg/kg IV every 8–12 hours PLUS ampicillin 2g IV every 4 hours (or amoxicillin 2g IV every 4 hours). 4, 1, 2, 3
• Ampicillin is mandatory because cephalosporins have no activity against Listeria monocytogenes, which accounts for significant morbidity in this population. 4, 1, 2
• Listeria risk factors include age >50 years, diabetes mellitus, immunosuppressive therapy, malignancy, alcohol misuse, and other immunocompromising conditions. 4, 1, 2, 3

Adjunctive Dexamethasone Therapy

• Dexamethasone 10 mg IV every 6 hours for 4 days should be administered to all adults with suspected bacterial meningitis. 1, 2, 5, 6
• Timing is critical: give dexamethasone 10–20 minutes before or simultaneously with the first antibiotic dose; if omitted initially, it may still be started within 4–12 hours after antibiotics. 2, 5, 6
• Evidence of benefit: dexamethasone reduces unfavorable outcomes from 25% to 15% and mortality from 15% to 7% in adults with bacterial meningitis, with the greatest effect in pneumococcal meningitis (mortality reduced from 34% to 14%). 5, 6
• Discontinue dexamethasone if Listeria is identified, as adjunctive steroids are associated with increased mortality in neurolisteriosis. 2
• Continue for the full 4 days when pneumococcal or H. influenzae meningitis is confirmed or highly probable; discontinue if an alternative etiology is identified. 2, 5, 6

Severe β-Lactam or Penicillin Allergy

• For true anaphylactic allergy to penicillins or cephalosporins, use chloramphenicol 25 mg/kg IV every 6 hours as the primary alternative. 4
• In children with severe β-lactam allergy, vancomycin plus rifampicin provides adequate coverage for typical bacterial pathogens. 3
• For adults with severe allergy, consider vancomycin 15–20 mg/kg IV every 8–12 hours plus moxifloxacin 400 mg IV daily to cover pneumococci and meningococci, and add trimethoprim-sulfamethoxazole 10–20 mg/kg/day (of trimethoprim component) in 4 divided doses for Listeria coverage in patients ≥50 years or immunocompromised. 4, 2

Regional Resistance Considerations

• If the patient has traveled to areas with high pneumococcal resistance within the past 6 months (check http://bit.ly/1rOb3cx for current data), add vancomycin 15–20 mg/kg IV every 12 hours OR rifampicin 600 mg IV/PO every 12 hours to the cephalosporin regimen. 4, 1
• In regions where cephalosporin resistance (MIC >2 mg/L) is unlikely, ceftriaxone/cefotaxime alone may be considered, but adding vancomycin is recommended as a safety measure. 2, 3

Duration of Therapy by Pathogen

Pathogen	Definitive Antibiotic	Duration
Streptococcus pneumoniae	Ceftriaxone 2g IV q12h or cefotaxime 2g IV q6h	10–14 days [1,2,3]
Neisseria meningitidis	Ceftriaxone 2g IV q12h or cefotaxime 2g IV q6h	5–7 days [1,2,3]
Haemophilus influenzae	Ceftriaxone 2g IV q12h or cefotaxime 2g IV q6h	10 days [1,3]
Listeria monocytogenes	Amoxicillin 2g IV q4h (cephalosporins ineffective)	21 days [1,2,3]
Unknown pathogen (culture-negative)	Continue empiric regimen	10 days minimum [3]

Critical Pitfalls to Avoid

• Never delay antibiotics for imaging—if CT is indicated, administer antibiotics first, then obtain the scan. 1, 2, 3
• Never omit ampicillin in patients ≥50 years or immunocompromised—this is the single most common error leading to fatal Listeria infection. 4, 1, 2
• Never use cefepime instead of ceftriaxone or cefotaxime—cefepime has inferior CSF penetration and pneumococcal coverage for meningitis. 1
• Never underdose antibiotics—meningitis requires high-dose regimens to achieve adequate CSF concentrations; standard dosing leads to treatment failure. 1, 2, 3
• Never administer dexamethasone more than 12 hours after the first antibiotic dose—late administration provides no benefit. 2, 5
• Never stop antibiotics prematurely based on clinical improvement alone—complete the pathogen-specific duration to prevent relapse and complications. 3

Treatment Failure at 72 Hours

• Verify adequate vancomycin CSF levels (target 5–10 µg/mL in CSF) and consider adding rifampicin 600 mg IV/PO every 12 hours if not already included. 1
• Repeat lumbar puncture to assess CSF sterilization and confirm the diagnosis. 4
• Obtain infectious disease consultation for consideration of alternative or combination therapy. 1