What is the appropriate treatment for meningitis with elevated Acute Phase Reactant (APR) protein levels?

Treatment of Meningitis with Elevated Acute Phase Reactant Protein Levels

Immediate Empiric Antibiotic Therapy

When acute phase reactant (APR) protein levels are elevated in suspected meningitis—whether viral or bacterial—you must initiate empiric antibacterial therapy immediately, as elevated protein cannot reliably distinguish between bacterial and viral etiologies, and delay in treating bacterial meningitis significantly increases mortality and neurological morbidity. 1, 2, 3

Critical Time-Sensitive Actions (Within First Hour)

• Antibiotics must be administered within 1 hour of hospital arrival, as treatment delay is strongly associated with death and poor neurological outcomes 1, 2, 3
• Obtain blood cultures immediately before antibiotics, but do not delay treatment beyond 1 hour to obtain them 1, 2
• If lumbar puncture cannot be performed within 1 hour, start antibiotics immediately after blood cultures and perform LP afterward 1, 2
• In patients with predominantly sepsis or rapidly evolving rash, give antibiotics immediately after blood cultures without waiting for LP 1

Age-Based Empiric Antibiotic Regimens

For adults <50 years without Listeria risk factors:

• Ceftriaxone 2g IV every 12 hours (or cefotaxime 2g IV every 6 hours) 1, 2, 4
• PLUS vancomycin 15-20 mg/kg IV every 8-12 hours 1, 2, 4

For adults ≥50 years or immunocompromised:

• Ceftriaxone 2g IV every 12 hours (or cefotaxime 2g IV every 6 hours) 1, 2, 3
• PLUS vancomycin 15-20 mg/kg IV every 8-12 hours 1, 2, 3
• PLUS amoxicillin 2g IV every 4 hours for Listeria coverage 1, 2, 3

The rationale for this approach is that ceftriaxone provides essential coverage for the two most common causes (Streptococcus pneumoniae and Neisseria meningitidis), while vancomycin covers penicillin-resistant and cephalosporin-resistant pneumococci 2, 4. Amoxicillin is added in older adults because Listeria monocytogenes risk increases with age >50 years, diabetes, immunosuppressive drugs, cancer, and other immunocompromising conditions 2, 3.

Mandatory Adjunctive Corticosteroid Therapy

• Dexamethasone 10 mg IV every 6 hours should be administered immediately, either 10-15 minutes before or simultaneously with the first antibiotic dose 1, 2, 4, 3
• Continue dexamethasone for 4 days if pneumococcal meningitis is confirmed or thought probable based on clinical, epidemiological, and CSF parameters 1
• Stop dexamethasone if another cause of meningitis is confirmed or thought probable 1
• Dexamethasone reduces mortality and neurological morbidity, particularly in pneumococcal meningitis 1, 2, 4, 3

Pathogen-Specific Treatment Duration (Once Identified)

For Streptococcus pneumoniae:

• Continue ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours 1, 2
• If penicillin-sensitive (MIC ≤0.06 mg/L), may use benzylpenicillin 2.4g IV every 4 hours 1
• If penicillin and cephalosporin resistant, continue ceftriaxone/cefotaxime PLUS vancomycin 15-20 mg/kg IV every 12 hours PLUS rifampicin 600 mg IV/PO every 12 hours 1
• Duration: 10 days if recovered by day 10; extend to 14 days if not recovered or if resistant organism 1, 2

For Neisseria meningitidis:

• Continue ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours 1, 2
• Benzylpenicillin 2.4g IV every 4 hours is an alternative 1
• If not treated with ceftriaxone, give single dose ciprofloxacin 500 mg PO for eradication 1, 3
• Duration: 5-7 days if recovered 1, 2

For Listeria monocytogenes:

• Amoxicillin 2g IV every 4 hours 1, 2
• Alternative: co-trimoxazole 10-20 mg/kg (of trimethoprim component) in 4 divided doses 1
• Duration: 21 days 1, 2

For Haemophilus influenzae:

• Ceftriaxone 2g IV every 12 hours or cefotaxime 2g IV every 6 hours 1, 2
• Alternative: moxifloxacin 400 mg IV once daily 1
• Duration: 10 days 1, 2

Critical Care Considerations

Transfer to ICU if patient has: 1, 3

• Rapidly evolving rash 1, 3
• Glasgow Coma Scale ≤12 (or drop of >2 points) 1, 3
• Requiring monitoring or specific organ support 1, 3
• Uncontrolled seizures 1, 3
• Cardiovascular instability, acid/base disturbance, hypoxia, or respiratory compromise 1, 3

Strongly consider intubation if GCS <12 1, 3

Common Pitfalls to Avoid

• Never delay antibiotics for imaging or lumbar puncture—treatment delay beyond 1 hour significantly increases mortality 1, 2, 4, 3
• Do not use ceftriaxone monotherapy—vancomycin must be added for adequate pneumococcal coverage given resistance patterns 2, 4
• Do not omit dexamethasone—it must be given before or with the first antibiotic dose to maximize benefit 1, 2, 4
• Do not fail to add amoxicillin in patients ≥50 years or immunocompromised—Listeria coverage is essential in these populations 1, 2, 3
• Do not stop antibiotics prematurely based on clinical improvement alone—complete the pathogen-specific duration to prevent relapse 2
• Do not use diluents containing calcium (such as Ringer's solution) with ceftriaxone, as precipitation can occur 5
• In neonates, infuse ceftriaxone over 60 minutes (not 30 minutes) to reduce risk of bilirubin encephalopathy 5

Special Considerations for Antibiotic Resistance

• Add vancomycin 15-20 mg/kg IV every 12 hours OR rifampicin 600 mg every 12 hours if penicillin resistance is suspected (e.g., patient recently arrived from country with high pneumococcal resistance) 1
• Molecular diagnostics such as PCR can detect pathogens up to 9 days after antibiotics have been given, though they do not provide antibiotic susceptibilities 1