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Published on: February 14, 2020
Bacterial Brain Abscesses Expand Despite Effective Antibiotic Treatment: A Process Powered by Osmosis Due to
Daniel Dahlberg1, Sverre Holm2, Ellen Margaret Lund Sagen2,3
1Department of Neurosurgery, Oslo University Hospital, Oslo , Norway.
Background And Objectives:
A bacterial brain abscess is an emergency and should be drained of pus within 24 hours of diagnosis, as recently recommended. In this cross-sectional study, we investigated whether delaying pus drainage entails brain abscess expansion and what the underlying mechanism might be.
Methods:
Repeated brain MRI of 47 patients who did not undergo immediate pus drainage, pus osmolarity measurements, immunocytochemistry, proteomics, and 18 F-fluorodeoxyglucose positron emission tomography.
Results:
Time from first to last MRI before neurosurgery was 1 to 14 days. Abscesses expanded in all but 2 patients: The median average increase was 23% per day (range 0%-176%). Abscesses expanded during antibiotic therapy and even if the pus did not contain viable bacteria. In a separate patient cohort, we found that brain abscess pus tended to be hyperosmolar (median value 360 mOsm; range 266-497; n = 14; normal cerebrospinal fluid osmolarity is ∼290 mOsm). Hyperosmolarity would draw water into the abscess cavity, causing abscess expansion in a ballooning manner through increased pressure in the abscess cavity. A mechanism likely underlying pus hyperosmolarity was the recruitment of neutrophils to the abscess cavity with ensuing neutrophil cell death and decomposition of neutrophil proteins and other macromolecules to osmolytes: Pus analysis showed the presence of neutrophil proteins (protein-arginine deiminases, citrullinated histone, myeloperoxidase, elastase, cathelicidin). Previous studies have shown very high levels of osmolytes (ammonia, amino acids) in brain abscess pus. 18 F-fluorodeoxyglucose positron emission tomography showed focal neocortical hypometabolism 1 to 8 years after brain abscess, indicating long-lasting damage to brain tissue.
Conclusion:
Brain abscesses expand despite effective antibiotic treatment. Furthermore, brain abscesses cause lasting damage to surrounding brain tissue. These findings support drainage of brain abscesses within 24 hours of diagnosis.
Insights
Delaying bacterial brain abscess drainage leads to significant expansion, even with antibiotics. This expansion is driven by hyperosmolar pus, causing lasting brain damage and supporting urgent 24-hour drainage recommendations.
Area of Science:
- Neurology
- Infectious Diseases
- Radiology
Background:
- Bacterial brain abscess requires prompt pus drainage within 24 hours of diagnosis.
- Delayed drainage may lead to abscess expansion and neurological damage.
Purpose of the Study:
- To investigate brain abscess expansion when pus drainage is delayed.
- To explore the underlying mechanisms of abscess expansion.
Main Methods:
- Repeated brain MRI in 47 patients without immediate drainage.
- Pus osmolarity, immunocytochemistry, proteomics, and 18F-fluorodeoxyglucose positron emission tomography were utilized.
Main Results:
- Abscesses expanded in 45/47 patients, with a median daily increase of 23%.
- Expansion occurred despite antibiotic therapy and even in the absence of viable bacteria.
- Hyperosmolar pus, caused by neutrophil decomposition, draws water into the abscess, driving expansion.
- 18F-FDG PET revealed long-lasting brain damage (hypometabolism) years after abscess resolution.
Conclusions:
- Brain abscesses expand irrespective of antibiotic treatment efficacy.
- Delayed drainage contributes to lasting brain tissue damage.
- Findings reinforce the recommendation for prompt (within 24 hours) surgical drainage of brain abscesses.
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