Bacterial Brain Abscesses Expand Despite Effective Antibiotic Treatment: A Process Powered by Osmosis Due to Neutrophil Cell Death

Neurosurgery 94:1079–1087, 2024

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.

Spontaneous empyema and brain abscess in an intensive care population: clinical presentation, microbiology, and factors associated with outcome

Acta Neurochirurgica (2023) 165:651–658

Data on critically ill patients with spontaneous empyema or brain abscess are limited. The aim was to evaluate clinical presentations, factors, and microbiological findings associated with the outcome in patients treated in a Neurocritical Care Unit.

Methods In this retrospective study, we analyzed 45 out of 101 screened patients with spontaneous epidural or subdural empyema and/or brain abscess treated at a tertiary care center between January 2012 and December 2019. Patients with postoperative infections or spinal abscess were excluded. Medical records were reviewed for baseline characteristics, origin of infection, laboratory and microbiology findings, and treatment characteristics. The outcome was determined using the Glasgow outcome scale extended (GOSE).

Results Favorable outcome (GOSE 5–8) was achieved in 38 of 45 patients (84%). Four patients died (9%), three remained severely disabled (7%). Unfavorable outcome was associated with a decreased level of consciousness at admission (Glasgow coma scale < 9) (43% versus 3%; p = 0.009), need of vasopressors (71% versus 11%; p = 0.002), sepsis (43% versus 8%; p = 0.013), higher age (65.1 ± 15.7 versus 46.9 ± 17.5 years; p = 0.014), shorter time between symptoms onset and ICU admission (5 ± 2.4 days versus 11.6 ± 16.8 days; p = 0.013), and higher median C-reactive protein (CRP) serum levels (206 mg/l, range 15–259 mg/l versus 17.5 mg/l, range 3.3–72.7 mg/l; p = 0.036). With antibiotics adapted according to culture sensitivities in the first 2 weeks, neuroimaging revealed a progression of empyema or abscess in 45% of the cases.

Conclusion Favorable outcome can be achieved in a considerable proportion of an intensive care population with spontaneous empyema or brain abscess. Sepsis and more frequent need for vasopressors, associated with unfavorable outcome, indicate a fulminant course of a not only cerebral but systemic infection. Change of antibiotic therapy according to microbiological findings in the first 2 weeks should be exercised with great caution.

Hyperbaric oxygen therapy in spontaneous brain abscess patients

Hyperbaric oxygen therapy in spontaneous brain abscess patients

Acta Neurochir (2016) 158:1259–1267

There is a need to improve outcome in patients with brain abscesses and hyperbaric oxygen therapy (HBOT) is a promising treatment modality. The objective of this study was to evaluate HBOT in the treatment of intracranial abscesses.

Method This population-based, comparative cohort study included 40 consecutive adult patients with spontaneous brain abscess treated surgically between January 2003 and May 2014 at our institution. Twenty patients received standard ther- apy with surgery and antibiotics (non-HBOT group), while the remaining 20 patients also received adjuvant HBOT (HBOT group).

Results Resolution of brain abscesses and infection was seen in all patients. Two patients had reoperations after HBOT
initiation (10 %), while nine patients (45 %) in the non- HBOT group underwent reoperations (p = 0.03). Of the 26 patients who did not receive HBOT after the first surgery, 15 (58 %) had one or several recurrences that lead to a new treatment: surgery (n = 11), surgery + HBO (n = 5) or just HBO (n = 1). In contrast, recurrences occurred in only 2 of 14 (14 %) who did receive HBOT after the first surgery (p < 0.01). A good outcome (Glasgow Outcome Score [GOS] of 5) was achieved in 16 patients (80 %) in the HBOT cohort versus 9 patients (45 %) in the non-HBOT group (p = 0.04).

Conclusions HBOT was associated with less treatment failures and need for reoperation and seemingly with improved long-term outcome. Further, HBOT was well tolerated and safe. Prospective studies are warranted to establish the role of HBOT in the treatment of brain abscesses.

Supratentorial and infratentorial brain abscesses: surgical treatment, complications and outcomes—a 10-year single-center study

Acta Neurochir (2012) 154:903–911. DOI 10.1007/s00701-012-1299-z

To analyze the variables determining morbidity, mortality and outcome in subjects with brain abscesses treated at a single center over a 10-year period.

Methods A retrospective study was conducted on a series of 59 patients with brain abscesses surgically treated with stereotactically guided aspiration or open craniotomy excision. Such variables as age, gender, clinical presentation, number of days to diagnosis, location, number of lesions, predisposing factors, mechanism of infection, etiological agent, and therapy were analyzed independently. Complications were defined as any deviation from the normal postoperative course occurring within 30 days of surgery, and classified according to a four-point gradual severity scale. Postoperative outcome was appraised through the Glasgow Outcome Scale (GOS) 6 months after surgery, 0–4 points were considered poor outcome and 5 points good outcome.

Results Eighty abscesses were diagnosed and surgically managed in 59 patients. The mean age was 44.69 years (range: 0.16-77); 59.3% were female. The median number of days to diagnosis was 7. Most frequent clinical presentations included fever (52.5%), headache (42.4%), and focal neurologic deficits (39%). Mechanism of infection was mainly hematogenous spread (32.2%). Stereotactically guided aspiration was the treatment of choice for 74.6% of the patients, whereas 25.4% of the cases were managed through open craniotomy excision. Outcome was favorable in 81.35% (n048) of the subjects. General morbidity was 27.1%, and mortality stood at 10.16%. Out of a total 38.98% (n023) of complications, two-thirds were due to medical causes. The analysis of variables revealed that only age (p00.02), immunosuppression (OR 5.83; p00.012) and hematogenous spread (p<0.01) were associated with poor outcomes.

Conclusions Immunosuppression, hematogenous spread and advanced age were predictors of poor prognosis. Most of the complications following brain abscess management were not directly related to surgery or surgical technique.