Antibiotic therapy, endotoxin concentration in cerebrospinal fluid, and brain edema in experimental Escherichia coli meningitis in rabbits
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Abstract:
We investigated the effect of cefotaxime and chloramphenicol on endotoxin concentrations in cerebrospinal fluid (CSF) and on the development of brain edema in rabbits with Escherichia coli meningitis. Both antibiotics were similarly effective in reducing bacterial titers. Cefotaxime, but not chloramphenicol, induced a marked increase of endotoxin in CSF, from log10 1.5 +/- 0.8 to log10 2.8 +/- 0.7 ng/ml (P less than .01). This result was associated with an increase in brain water content (405 +/- 12 g of water/100 g of dry weight compared with 389 +/- 8 g in untreated controls; P less than .01), whereas in animals treated with chloramphenicol, brain water content was identical to controls. The cefotaxime-induced increase in endotoxin concentration and brain edema were both neutralized by polymyxin B, which binds to the lipid A moiety of endotoxin, or by a monoclonal antibody to lipid A. These results indicate that treating gram-negative bacillary meningitis with selected antibiotics induces increased endotoxin concentrations in CSF that are associated with brain edema.
Insights
Certain antibiotics like cefotaxime increase endotoxin levels in cerebrospinal fluid (CSF), worsening brain edema in bacterial meningitis. Chloramphenicol did not cause this effect, suggesting antibiotic choice impacts meningitis outcomes.
Area of Science:
- Infectious Diseases
- Neuroscience
- Pharmacology
Background:
- Bacterial meningitis, particularly gram-negative bacillary meningitis, poses significant risks.
- Antibiotic treatment is crucial but can have unintended consequences.
- Endotoxin release and subsequent brain edema are key pathological features.
Purpose of the Study:
- To investigate the impact of cefotaxime and chloramphenicol on endotoxin levels in cerebrospinal fluid (CSF).
- To determine the effect of these antibiotics on the development of brain edema in rabbits with Escherichia coli meningitis.
- To explore potential mechanisms and interventions related to antibiotic-induced endotoxin changes.
Main Methods:
- Experimental meningitis was induced in rabbits using Escherichia coli.
- Animals were treated with either cefotaxime or chloramphenicol.
- Cerebrospinal fluid (CSF) endotoxin concentrations and brain water content were measured.
- Intervention with polymyxin B or a monoclonal antibody to lipid A was assessed.
Main Results:
- Both cefotaxime and chloramphenicol effectively reduced bacterial titers.
- Cefotaxime significantly increased CSF endotoxin concentrations, unlike chloramphenicol.
- The increase in endotoxin by cefotaxime was associated with a significant rise in brain edema.
- Polymyxin B or anti-lipid A antibody neutralized cefotaxime's effects on endotoxin and edema.
Conclusions:
- Antibiotic treatment for gram-negative meningitis can elevate CSF endotoxin levels.
- This elevation is linked to increased brain edema, as demonstrated with cefotaxime.
- Chloramphenicol does not appear to induce this adverse effect.
- Targeting endotoxin, specifically its lipid A moiety, may mitigate antibiotic-associated complications in meningitis.