What is the epidemiology of bacterial intracerebral abscess in Europe/US?

We identified 51 studies reporting bacterial causes of brain abscesses that met the inclusion criteria.^63-112,113 In these studies 3,583 patients were included (table 2). In 2536 patients (71%) data on bacterial cultures were provided, and in 435 patients no culture was performed (17%). Cultures were negative in 30% and in studies reporting the number of cultured bacteria, 26% of the cultures were polymicrobial. This may be an underestimation as local microbiology data suggest that the rate of polymicrobial intracranial abscesses may be as high as 50%.

Of the 2,653 bacteria cultured in the included studies, Streptococcus species were the most prevalent and were identified in 36% of the positive cultures (table 3). Specification of streptococcal species was not available for the majority of strains. Streptococci from the milleri group were the most frequently identified species, occurring in 9% of all patients and 72% of specified streptococcal species. S. pneumoniae, the most frequent pathogen of bacterial meningitis, was identified in only 3% of all positive cultures in brain abscess patients.⁶ The second most common microorganisms identified in brain abscesses were Staphylococcus species (frequency 17%). Staphylococcus aureus was identified in 11% of patients and Staphylococcus epidermidis in 2%. The species were not specified of the remaining strains. Gram negative enteric bacteria were found in 12% of cases and most of these were Proteus spp. (7%). Other relatively frequent pathogens were Bacteroides spp. (7%), Haemophilus spp (3%) and Peptostreptococcus spp (3%). In these included studies 17% of bacteria were classified as ‘other’ or were not specified. 

Anaerobe bacteria are present in virtually all polymicrobial abscesses and are frequently found in cerebral abscesses with a dentogenic focus. The frequency of anaerobes given in Supplementary table 3 may be an underestimation due to suboptimal culture techniques and transportation. 

16S ribosomal DNA sequencing has expanded the yield of microbiological investigation in patients with intracerebral abscesses.¹¹⁴ The number of causative pathogens identified by sequencing of brain abscess aspirate was over threefold higher compared to standard culture techniques (22 strains identified by culture vs. 72 by sequencing).¹¹⁴ This technique is currently not commonly used, but will probably become part of routine diagnostics in the coming years.

What is the optimal (empirical) antibiotic therapy in intracerebral abscess?

No clinical trials have been performed to determine the optimal regimen in bacterial intracerebral abscesses, therefore the recommendations are all based on expert opinion.^8,9 Empirical treatment consists of a third generation cephalosporin (ceftriaxone or cefotaxime) combined with metronidazole in appropriate doses to penetrate the blood brain barrier. Alternatively penicillin may be used instead of third generation cephalosporins. After identification of the causative microorganism the antimicrobial therapy can be adapted according to the antimicrobial resistance pattern. In culture-negative cases the empirical therapy should be continued until clinical resolution (see question "What is the optimal duration of therapy?").

The primary source of infection can give a clue to which bacteria cause the cerebral abscesses. For instance, Enterobacteriaceae are the most frequently found in cerebral abscesses due to otogenic infections. However, since virtually all common pathogens have been reported for the various sources of infection, the choice of empirical antimicrobial therapy cannot be guided by the source of infection (e.g. dental abscess, endocarditis). 

What is the optimal dose of antimicrobial therapy?

Only a limited number of antimicrobials have been studied for their penetration into brain abscesses, mostly in small studies.⁵³Antimicrobials have to be able to first penetrate the blood brain barrier and then to achieve sufficient levels inside the abscess to resolve the infection. Penicillin concentrations were only found consistently in brain abscess pus if administered in a high dose of 24 million units per day.¹¹⁵Commonly advised doses of penicillin are however 12 million units per day in adults.^8,9 Other antimicrobials that have shown adequate or good penetration into the abscess cavity are metronidazole, vancomycin and third generation cephalosporins.⁵³ The dosage and dose intervals of antimicrobials commonly used for brain abscesses are presented in table 1. For vancomycin and aminoglycosides, the dose needs to be adjusted according to the peak and trough serum concentrations.

Table 1 Dosages of antibiotics for use in adults with bacterial brain abscesses.^a

Adapted from⁸. ^aPatients with normal hepatic and renal function, intravenous administration. ^bAdjust dosage based on peak and trough serum concentrations. 

What is the optimal duration of therapy?

No studies have been performed to evaluate the optimal duration of therapy in bacterial brain abscesses. The common strategy is to treat the abscess at least 6 weeks and to use clinical, laboratory and radiological follow-up data to decide on further  treatment beyond this period.^8,9 Studies on antimicrobial treatment duration for cerebral abscesses are needed.

Table 2 Culture results presented in 51 studies on intracerebral abscesses including 3583 patients.

Table 3