Vancomycin Coverage in Meningitis
Vancomycin in meningitis primarily covers penicillin-resistant and cephalosporin-resistant Streptococcus pneumoniae, and is also the agent of choice for methicillin-resistant Staphylococcus aureus (MRSA) meningitis. 1
Primary Organisms Covered
Streptococcus pneumoniae (Pneumococcus)
- Vancomycin is specifically indicated for pneumococcal strains with reduced susceptibility to penicillin (MIC >0.06 mg/L) or cephalosporins (MIC >0.5 mg/L). 1
- It provides coverage when pneumococci are resistant to both penicillin and third-generation cephalosporins, requiring combination therapy with ceftriaxone/cefotaxime plus vancomycin 15-20 mg/kg IV every 12 hours plus rifampicin 600 mg every 12 hours. 1
- Vancomycin should be added empirically if the patient has recently traveled to regions with high pneumococcal resistance rates (check within the last 6 months). 1, 2
Staphylococcus aureus
- Vancomycin is the recommended agent for methicillin-resistant S. aureus (MRSA) meningitis. 1
- For methicillin-sensitive S. aureus, flucloxacillin or nafcillin are preferred, but vancomycin remains an alternative. 1
- Treatment duration for staphylococcal meningitis should be at least 14 days. 1
Critical Pharmacological Limitations
Poor CSF Penetration
- Vancomycin has notoriously poor cerebrospinal fluid penetration: approximately 1% with uninflamed meninges and only 5% with inflamed meninges, achieving maximum CSF concentrations of only 2-6 μg/mL. 2, 3
- Despite inflammation improving penetration to approximately 20%, this remains suboptimal compared to other agents. 4
- The FDA label confirms that vancomycin "does not readily diffuse across normal meninges into the spinal fluid; but, when the meninges are inflamed, penetration into the spinal fluid occurs." 3
Never Use as Monotherapy
- Vancomycin should NEVER be used alone for meningitis due to poor CSF penetration and documented treatment failures. 1, 2
- In one clinical study of 11 adults with pneumococcal meningitis treated with vancomycin monotherapy, 4 patients (36%) experienced therapeutic failure requiring a change in antibiotics. 5
- Vancomycin must always be combined with a third-generation cephalosporin (ceftriaxone or cefotaxime) for adequate coverage. 1, 2
Organisms NOT Covered by Vancomycin
Critical Gaps in Coverage
- Vancomycin has NO activity against gram-negative bacilli, including Neisseria meningitidis, Haemophilus influenzae, and Enterobacteriaceae. 3
- It does not cover Listeria monocytogenes, which requires ampicillin or amoxicillin. 1
- Vancomycin is not active against mycobacteria or fungi. 3
Recommended Empiric Regimens
When to Add Vancomycin
- Add vancomycin to third-generation cephalosporin therapy in the following scenarios: 1, 2
- Recent travel (within 6 months) to areas with high pneumococcal resistance rates
- Known local prevalence of penicillin-resistant pneumococci
- Suspected or confirmed MRSA infection
- Immunocompromised patients at higher risk for resistant organisms
Standard Dosing
- Vancomycin 15-20 mg/kg IV every 12 hours, targeting serum trough concentrations of 15-20 μg/mL. 1, 2
- Higher doses may be needed to overcome poor CSF penetration, particularly when dexamethasone is co-administered (which further reduces vancomycin penetration by 29%). 4
Important Clinical Pitfalls
Steroid Interaction
- Dexamethasone significantly reduces vancomycin CSF penetration by approximately 29%, potentially compromising efficacy. 4
- This effect may be circumvented by using larger daily doses of vancomycin (40 mg/kg/day in divided doses). 4
Combination Therapy is Essential
- Animal studies demonstrate that ceftriaxone combined with vancomycin is synergistic against cephalosporin-resistant pneumococci, with significantly better CSF sterilization rates than monotherapy. 6, 7
- The addition of rifampicin to vancomycin further enhances bactericidal activity, as rifampicin achieves 22% CSF penetration. 2, 7