A2 – SGD 8

Question # 2

Which antibiotic regimens achieve therapeutic concentrations in the cerebrospinal fluid

and which should be avoided?

Answer:

• The degree of serum protein binding correlates well with the extent of CSF
penetration. Ceftriaxone is highly bound to serum proteins and thus, they are more
confined to the intravascular space and not as readily available for CSF penetration
as cefotaxime and ceftazidime, which are protein bound to a lesser extent.
Ceftriaxone achieves sustained, reliable bactericidal activity within the CSF despite
its high protein binding. Ceftriaxone has been used successfully to treat meningitis in
both children and adults for many years.

• Vancomycin and polymyxin B do not diffuse well across the blood-CSF barrier,
primarily because of their large molecular size. Therapeutic concentrations in the
CSF ( upto 22% of serum concentrations) are attained with systemic vancomycin
therapy when the meninges are inflamed.

• The commonly prescribed antimicrobials, clindamycin and erythromycin, penetrate

the CSF poorly, and they have limited usefulness because of their bacteriostatic
mode of action.

• Fluoroquinolones, such as ciprofloxacin and ofloxacin, penetrate reasonably well into

the CSF on a percentage basis(~20-30%) ; however, the concentrations attained are
fairly low (<1 meg/mL) when standard doses are administered.