ANTIBIOTIK

BLOOD BRAIN BARRIER

Noor Wijayahadi
 The blood-brain barrier (BBB)
Capillaries in brain have tight junctions that
contribute to the BBB.

Capillaries in brain are wrapped by

pericapillary glial cells that further contribute
to the BBB.

The endothelial cells in brain capillaries have

P-glycoprotein that pumps drugs out of
endothelial cells, and this also contributes to
the BBB.
 The blood-brain barrier (BBB)

BBB restricts the movement of hydrophilic

drugs into brain

BBB is broken by ischemia and

inflammation.

BBB can be exploited to develop drugs with

reduced CNS adverse effects.
WHAT IS THE EFFECT OF ION TRAPPING
ON DRUG DISTRIBUTION?

Compartment Compartment
with Low pH with High pH

BIOLOGICAL BARRIER
Unionized Unionized
Weak Acid Weak Acid
Higher total
concentration
of weak acid
Ionized Ionized
Weak Acid
Weak Acid
 WHAT IS THE EFFECT OF ION TRAPPING
ON DRUG DISTRIBUTION?

Compartment Compartment
with Low pH with High pH

BIOLOGICAL BARRIER
Unionized Unionized
Weak Base Weak Base

Higher total
concentration
of weak base
Ionized Ionized
Weak Base

Weak Base
(hydroxyl group)

(amine group)
Distribution: Depends on Blood Flow and Blood
Brain Barrier
 Excludes ionized
substances;
Active transport
mechanisms;
Not uniform leaky
(circumventricular
areas)
KUMAN GRAM (+)
 Penisilin
Narrow-spectrum
Penicillin G (IV)
Penicillin VK (PO)
Penicillinase-resistant Antistaphylococcal
Cloxacillin, dicloxacillin (PO)
Nafcillin (IV)
Oxacillin (IV)
Extended-spectrum
Ampicillin/.Amoxicillin (PO)
Amoxicillin + clavulanate (PO)
Piperacillin (IV)
Ticarcillin (IV)
 Cephalosporins

1st Gram (+)

2nd spektrum lebih luas Gr (-) Gr (+)
3rd spektrum Gr (-) Gr (+)
Serious Gram negative infections
CeftriAXone and cefotAXime meningitis
Ceftazidime anti-Pseudomonal
4th cefepime Anti-Pseudomonal coverage
Spektrum Gr (-)/Gr (+) baik
5th Ceftaroline
MRSA
 Vancomycin

The emergence of penicillin and cephalosporin resistant

strains of S. pneumo has resulted in increased use of
Vancomycin for treatment of bacterial meningitis

CNS Penetration: ~ 10% of serum concentration

Pharmacodynamics: Studies in rabbits suggest that

maximal bacterial killing rate (BKR) is achieved when
vancomycin levels are 5-10x the Minimal Bactericidal
Concentration (MBC) [CID 1998;27:1117-29]
 Vancomycin: Concerns about CNS
Penetration
Given that CNS penetration by hydrophilic antibiotics like
Vancomycin and Beta-lactams are dependent on
meningeal inflammation, concomitant use with high dose
steroids may reduce vancomycins penetration into the
CSF
In the setting of adjuvant corticosteroid therapy, larger doses
of vancomycin (40mg/kg BID) may be needed to achieve
and maintain therapeutic concentrations in the CSF
Vancomycin should be given at total daily doses of 30-
45mg/kg.
 Meropenem
A carbapenem antibiotic which is active against some
of the major pathogens causing meningitis

Pharmacokinetics:
CNS penetration: penetrates intact BBB poorly, but
with meningeal inflammation sufficiently high CSF
levels are achieved for bactericidal effect
Does not have epileptogenic activity like imipenem
 Linezolid
Nosocomial CNS infections are often caused by
resistant Gram positive bacteria.
Treatment with vancomycin may have some limitations
given its poor penetration, nephrotoxicity, and
possible resistance (VRE).

Linezolid penetration in CSF was 66%

Linezolid is not an ideal treatment of meningitis

because it is bacteriostatic.
DAYA PENETRASI ANTIBIOTIK
BBB