Antibiotics Used for Bacterial Meningitis in Children

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.

Drug Susceptibility

Drugs for specific antibiotic therapy for bacterial meningitis

Organism Recommended therapy Alternative therapy
S. pneumoniae    
Penicillin-sensitive Penicillin G Ampicillin or cefotaxime or ceftriaxone or chloramphenicol
Penicillin-resistant Cefotaxime or ceftriaxone Vancomycin or chloramphenicol
N. meningitidis    
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
L. monocytogenes Ampicillin Cotrimoxazole
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.

Drug Penetration

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.

Influencing factors

  • 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.