Treatment of Streptococcus pneumoniae Meningitis
For confirmed or suspected pneumococcal meningitis in adults, initiate ceftriaxone 2g IV every 12 hours (or cefotaxime 2g IV every 6 hours), and add vancomycin 15-20 mg/kg IV every 12 hours plus rifampicin 600mg twice daily if penicillin or cephalosporin resistance is suspected or confirmed. 1
Empiric Treatment Algorithm
Initial Therapy Based on Age and Risk Factors
Adults <60 years:
- Ceftriaxone 2g IV every 12 hours OR cefotaxime 2g IV every 6 hours 1
- Alternative: Chloramphenicol 25 mg/kg IV every 6 hours if cephalosporin allergy 1
Adults ≥60 years:
- Same cephalosporin regimen PLUS amoxicillin 2g IV every 4 hours (to cover Listeria monocytogenes) 1
- Alternative: Chloramphenicol 25 mg/kg every 6 hours AND co-trimoxazole 10-20 mg/kg (trimethoprim component) in four divided doses 1
Add Vancomycin or Rifampicin If:
- Patient traveled to areas with high penicillin-resistant pneumococcal prevalence within last 6 months 1
- Local resistance patterns suggest concern for resistant strains 1
- Dosing: Vancomycin 15-20 mg/kg IV every 12 hours (target trough 15-20 μg/mL) OR rifampicin 600mg IV/oral every 12 hours 1
Definitive Therapy After Organism Identification
Penicillin-Sensitive S. pneumoniae (MIC ≤0.06 mg/L):
- Continue ceftriaxone 2g every 12 hours OR cefotaxime 2g every 6 hours 1
- Alternative: Benzylpenicillin 2.4g IV every 4 hours 1
- Duration: 10 days if recovered by day 10; extend to 14 days if not recovered 1
Penicillin-Resistant but Cephalosporin-Sensitive (MIC >0.06 but ceftriaxone MIC ≤0.5 mg/L):
Dual Penicillin and Cephalosporin Resistance (ceftriaxone MIC >0.5 mg/L):
- Continue ceftriaxone 2g every 12 hours OR cefotaxome 2g every 6 hours 1
- PLUS vancomycin 15-20 mg/kg IV every 12 hours 1
- PLUS rifampicin 600mg IV/oral every 12 hours 1
- Duration: 14 days 1
Evidence Quality and Nuances
The UK Joint Specialist Societies guideline (2016) provides the most comprehensive and authoritative recommendations for pneumococcal meningitis treatment 1. These guidelines are based on known pharmacokinetics showing that third-generation cephalosporins achieve excellent CSF penetration and bactericidal activity against pneumococci 1.
Critical consideration: While a recent 2023 study suggested that ceftriaxone 2g once daily may have similar outcomes to 2g every 12 hours for highly susceptible strains 2, this contradicts established guideline recommendations. The guideline-recommended twice-daily dosing (total 4g daily) ensures sustained therapeutic CSF concentrations throughout the dosing interval 1. Follow guideline recommendations of 2g every 12 hours rather than once-daily dosing.
Experimental models demonstrate that vancomycin plus ceftriaxone shows synergistic or additive effects against highly resistant pneumococcal strains 3, 4. The combination of ceftriaxone plus vancomycin was bactericidal from 6 hours onward and significantly decreased inflammatory parameters compared to ceftriaxone alone 4.
Common Pitfalls to Avoid
- Do not reduce ceftriaxone to once-daily dosing during initial treatment, even after susceptibilities return showing sensitivity—maintain twice-daily dosing for the full treatment course 1
- Do not discontinue vancomycin prematurely if added for suspected resistance—continue for full 14-day course if resistance confirmed 1
- Do not use rifampicin monotherapy—resistance emerges rapidly; always combine with another active agent 4
- Do not forget Listeria coverage in patients ≥60 years—add amoxicillin empirically 1