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Positive Meningitis
Bhakti Patel
M4 Medical Therapeutics
Case (adapted from ID consult 8/2006)
Pharmacokinetics
The concentration of antibiotics in CSF depends on the balance
between drug penetration and elimination through the blood brain
barrier.
Choosing the Right Antibiotic
Crossing the Blood Brain Barrier
(CID 1998;27:1117-29)
Choosing the Right Antibiotic
Pharmacodynamics of Antibiotics in CSF
Gram
Positive
Organisms
ClD 2004;39:1267-84
Beta-Lactams
CNS penetration:
Beta lactams penetrate the intact BBB poorly
However in the presence of inflammation
penicillins can achieve levels greater than 10x the
minimal bactericidal concentration MBC90 for
gram positive pathogens (Inf Dis N Am. 1999; 13 (3): 595-611)
Pharmacodynamics
Exhibits time-dependent bactericidal activity
Vancomycin
The emergence of penicillin and cephalosporin resistant strains
of S. pneumo has resulted in increased use of Vancomycin
for treatment of bacterial meningitis
Pharmacokinetics:
IV, IM formulation only
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
(CID 1997;24 suppl2: S266-75)
Meropenem
A randomised comparison of meropenem with cefotaxime
or ceftriaxone for the treatment of bacterial meningitis in
adults (J Antimicrobial Chemo 1995; 36 Suppl A:85-97)
Experimental design:
56 patients were enrolled with half receiving meropenem and the rest a cephalosporin
(either ceftriaxone or cefotaxime 11 and 17 pts respectively)
Pts were assessed by neuro exam, GCS score, Herson-Todd score for measure of clinical
cure
Results:
Clinical cure was observed in 100% of meropenem treated group
and 77% of cephalosporin treatment group
Conclusions:
Meropenem is an effective and well-tolerated antibiotic for
treatment of adult bacterial meningitis at doses of 6g/day.
Linezolid
Nosocomial CNS infections (as described in the
case) 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 may be considered in these situations;
however its not an ideal treatment of
meningitis because it is bacteriostatic.
Linezolid
CNS penetration