Antibiotics are critical in the treatment of meningitis since the body’s immune response in the CNS for fighting the infection is limited. The blood-brain barrier limits delivery of antibodies and complement factors into the CSF. Phagocytosis of encapsulated bacteria in the CSF is thus decreased. Antibiotics must be able to reach high levels in the CSF, and these levels must be maintained at 10 to 20 times the minimal in vitro bactericidal concentrations in order to eradicate the infection. This is the basis for the recommended drugs and dosages presented below.
Drugs for specific antibiotic therapy for bacterial meningitis
|Organism||Recommended therapy||Alternative therapy|
|Penicillin-sensitive||Penicillin G||Ampicillin or cefotaxime or ceftriaxone or chloramphenicol|
|Penicillin-resistant||Cefotaxime or ceftriaxone||Vancomycin or chloramphenicol|
|Penicillin-sensitive||Penicillin G||Ampicillin or cefotaxime or ceftriaxone|
|Penicillin-resistant||Cefotaxime or ceftriaxone||Chloramphenicol|
|H. influenzae type b||Cefotaxime or ceftriaxone||Ampicillin or chloramphenicol|
|Group B streptococcus||Cefotaxime or ceftriaxone||Penicillin G or ampicillin plus aminoglycoside|
|E. coli, Klebsiella sp., Enterobacter sp.||Cefotaxime or ceftriaxone with or without aminoglycoside||Ampicillin or broad-spectrum carbapenem (i.e., meropenem)|
|Salmonella sp.||Cefotaxime or ceftriaxone||Ampicillin or cotrimoxazole or chloramphenicol|
|S. aureus, coagulase-negative Staphyloccus sp.|
|Methicillin-sensitive||Nafcillin or oxacillin or methacillin||Vancomycin in patients with penicillin allergy|
|Methicillin-resistant||Vancomycin||Vancomycin plus rifampin|
Recommended dosages of antibiotics for treatment of bacterial meningitis in neonates and children with normal renal function*
|Antibiotic||Dose in neonates||Dose in older infants and children||Maximum daily dose|
|Amikacin||15-22.5 mg/kg/day IV divided every 8-12 hours||15-22.5 mg/kg/day IV divided every 8-12 hours||750-1500 mg|
|Ampicillin||150-200 mg/kg/day IV divided every 6-12 hours||200-400 mg/kg/day IV divided every 6 hours||12 g|
|Cefotaxime||100-200 mg/kg/day IV or IM divided every 8-12 hours||200 mg/kg/day IV or IM divided every 6 hours||12 g|
|Ceftriaxone||80-100 mg/kg/day IV or IM every 24 hours||100 mg/kg/day IV divided every 12 hours, or 80 mg/kg/d IV every 24 hours||4 g|
|Chloramphenicol||75-100 mg/kg/day IV divided every 6 hours, or 75 mg/kg/day orally divided every 6 hours||2-4 g|
|Cotrimoxazole||10 mg/kg/day (as trimethoprim) IV divided every 8-12 hours||15 mg/kg/day (as trimethoprim) IV divided every 8 hours||1.2 g (as trimethoprim)|
|Gentamicin||5-7.5 mg/kg/day IV divided every 8-12 hours||7.5 mg/kg/day IV divided every 8 hours||240 mg|
|Nafcillin||150-200 mg/kg/day IV divided every 4-6 hours||9 g|
|Penicillin G||150,000 -300,000 units/kg/day IV divided every 6-8 hours||300,000-400,000 units/kg/day IV divided every 4 hours||20-24 million units|
|Vancomycin||30-45 mg/kg/day IV divided every 8-12 hours||45-60 mg/kg/day IV divided every 6 hours||2 g|
*Adjust dosages according to serum levels and clinical response as appropriate.
In addition to susceptibility of the organism to a given drug, penetration into the CSF to achieve sufficiently high bactericidal concentrations is critical to successful treatment.
- Inflammatory response: The inflammatory response caused by the bacterial infection increases passive diffusion of antibiotics through the blood-brain barrier. As meningeal inflammation decreases during recovery or after steroid administration, drug penetration may decline as well. One advantage of third-generation cephalosporins such as cefotaxime and ceftriaxone is their ability to achieve very high bactericidal levels in the CSF, so that the minor reduction in penetration with reduction in inflammation is insignificant. For drugs such as vancomycin, which rely more on opening of the blood-brain barrier with inflammation, this reduction may be significant.
- Drug lipid solubility: Lipophilic drugs including chloramphenicol, isoniazid, and rifampin enter the CSF more readily through the blood-brain barrier than the cephalosporins and aminoglycosides, which are less lipid soluble.
- Active transport of drug out of CSF: Active transport of antibiotics out of the CSF reduces the levels of drug in the CSF and makes maintenance of high CSF drug levels more difficult.