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Assessment of antibiotic efficacy in acute bacterial meningitis
Author(s) -
Beam Thomas R.,
Allen James C.
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1979252199
Subject(s) - choroid plexus , antibiotics , medicine , cerebrospinal fluid , meningitis , drug , cephalosporin , pharmacology , penicillin , chloramphenicol , microbiology and biotechnology , biology , surgery , central nervous system
Currently, antibiotic efficacy in acute bacterial meningitis is evaluated in several stages. First, animals are used to assess antibiotic penetration into cerebrospinal fluid (CSF) in the absence and presence of an inflammatory stimulus. Second, concentrations of drug are correlated to in vitro killing studies. Third, clinical evaluations compare the new drugs to currently available antimicrobics—but drug failures nevertheless occur, e.g. the experiences with cephalosporins and aminoglycosides. We propose that brain tissue levels of antibiotics are an additional parameter to be monitored. Drugs that penetrate the brain substance should yield higher ventricular concentrations than drugs that penetrate the choroid plexus alone. A protective benefit may also be afforded to brain tissue per se. Experience with chloramphenicol, which penetrates the blood‐brain barrier, supports these concepts; so also, do the failures with cephalosporins and aminoglycosides which, despite high CSF concentrations of these agents, afford, evidence that currently monitored parameters are inadequate predictors of therapeutic‐efficacy.