Focal Suppurative Infections of the Nervous System

Etiology

Bacteria cause >95% of brain abscesses in immunocompetent patients, including oral streptococci, Staphylococcus aureus , anaerobes, Enterobacteriaceae , and others. The Streptococcus milleri group ( S. constellatus, S. intermedius, and S. anginosus) comprise 50%–70% and staphylococci comprise 10%–30%. ^, Group A Streptococcus is rare. Streptococcus pneumoniae has declined as a cause of meningitis in the pneumococcal conjugate vaccine (PCV) era, but even in pre-PCV rarely caused brain abscess. ^, Up to 30% of suppurative CNS infections are polymicrobial by culture (up to 43% using molecular assays ^, ), often including nutritionally variant streptococci (e.g., Abiotrophia species ) or anaerobes (e.g., Bacteroides, Prevotella, and/or Peptostreptococcus spp.). Anaerobe detection classically require anaerobic culture methods, but new molecular methods improve detection rates.

Gram-negative organisms comprise 10%–25% of brain abscesses or subdural empyemas ( Table 46.1 ), most often otogenic in origin or occurring in young infants. ^, Citrobacter, ^, Salmonella , Serratia, Proteus , and Cronobacter species (previously Enterobacter sakazakii ) or Bacteroides fragilis are most frequent. C. sakazakii (associated with powdered formula) and Citrobacter koseri cause multifocal brain abscesses.

Chronic otitis media, uncontrolled diabetes mellitus, and iatrogenic neutropenia are risk factors for Pseudomonas aeruginosa or Proteus mirabilis . Impaired cell-mediated function, e.g., macrophage- or T-lymphocyte-related defects, or neutrophil phagocytic defects predispose to Listeria monocytogenes or Nocardia spp. ^,

Risk states for fungal brain abscesses include premature infants, congenital or acquired neutrophil defects, high-risk leukemias, transplantation (hematopoietic cell transplant [HCT] or solid organ transplant [SOT]), ^, or poorly controlled acquired immunodeficiency syndrome (AIDS). Over 90% of brain abscesses after HCT are fungal, usually Candida or Aspergillus spp. In premature infants, Candida spp. increasingly cause multiple small brain abscesses.

Prevalence of fungi in brain abscesses parallels other invasive fungal disease. Overall, Candida spp. are most common (42%), followed by Aspergillus (29%), other molds (14%), and Cryptococcus (4% and mostly in adults). Endemic fungi ( Histoplasma, Blastomyces, Coccidioides , 3%) occur predominantly in defined endemic geographic areas. Scedosporium spp. is seen increasingly, particularly in HCT recipients. Cryptococcus usually causes meningitis but can cause brain abscess. Other fungi rarely causing brain abscess are listed in Table 46.2 .

Protozoa causing brain abscess include Acanthamoeba, Schistosoma, or Paragonimus spp. With poorly controlled HIV in children, Toxoplasma gondii can rarely cause brain abscess. Entamoeba histolytica brain abscess is rare even with amebiasis. Helminthic migration ( Strongyloides stercoralis, Trichinella, or Taenia ) can cause brain abscesses or masses. Neurocysticercosis in patients from endemic areas (e.g., Mexico, Africa) causes single/multiple, often ring-enhancing, central nervous system (CNS) lesions often misconstrued as bacterial brain abscesses.

Table 46.2 lists other uncommon pathogens. Rarely, Mycoplasma or Ureaplasma spp. are causal. Mycobacterium tuberculosis brain abscess is purulent with acid-fast bacilli, differing from tuberculoma, which is a granulomatous mass with epithelioid and giant cells. Magnetic resonance imaging (MRI) differentiates these two conditions.

Location or distribution of lesion(s) suggests the pathogen. Frontal lobe (usually with concomitant sinusitis) suggests oral flora, i.e., Streptococcus spp. (aerobic, microaerophilic, anaerobic), staphylococci, and/or anaerobic bacteria ( Table 46.3 ). With penetrating trauma, S. aureus (often methicillin-resistant S. aureus, MRSA) increases but Streptococcus spp. remain more common. Temporal lobe or cerebellum suggests middle/external-ear pathogens and/or oral flora, or less often Enterobacteriaceae or Pseudomonas spp.

Hematogenous spread due to endocarditis, septic thrombophlebitis, lung abscess, pleural empyema, bronchiectasis (in cystic fibrosis), osteomyelitis, or skin infections classically produces multiple lesions in the distribution of the middle cerebral artery, but any pattern can be seen.

Hematogenous pathogens usually are S. aureus, aerobic or anaerobic streptococci, but rarely include Candida, Nocardia, Aspergillus, or Actinomyces spp. S. aureus is more frequent with prosthetic valve endocarditis or prolonged bacteremia (de novo or intravascular catheter associated). Aggregatibacter (formerly Haemophilus ) aphrophilus (a HACEK organism) is relatively common in patients with CCHD.

Pathogens of subdural empyema correlate with pathogenesis. In young children, subdural empyema usually accompanies bacterial meningitis (infrequent in countries with universal use of conjugate vaccines for Haemophilus influenzae type b [Hib], pneumococcus, and meningococcus) ( Table 46.2 ). ^,

Subdural empyemas not accompanying bacterial meningitis have the same pathogens as brain abscesses. Aerobic and anaerobic streptococci (e.g., S. intermedius and S. anginosus group) predominate when associated with sinusitis. S. aureus is more common postoperatively or post trauma but can occur after sinus/ear infection. Cultures are sterile in 20%–30%, likely due to: antibacterial pretreatment; nonviability of fastidious or anaerobic bacteria; or nonoptimal collection, transportation, or isolation procedures. Recent use of molecular diagnostics has allowed pathogen detection in culture negative samples.

Rare subdural pathogens include nontyphoidal Salmonella , S. pyogenes , Burkholderia , Brucella melitensis , Propionibacterium, Prevotella, fungi (e.g., Candida albicans, Pseudallescheria boydii ), or M. tuberculosis . Gram-negatives are increasingly detected in both subdural empyema and epidural abscess.

S. aureus is the most common cause of epidural abscess (cranial or spinal). ^, However, S. pneumoniae or S. agalactiae also cause cranial epidural abscesses. Cranial epidural abscesses occur in immunocompromised hosts due to Pseudallescheria, Aspergillus, ^, Candida spp., Zygomycetes, or M. tuberculosis . Spinal epidural abscess rarely is due to B. melitensis (Middle Eastern and Mediterranean area), Nocardia asteroides group, Actinomyces israelii, Cryptococcus neoformans, or Aspergillus. Epidural and other paravertebral abscess can complicate Bartonella henselae vertebral osteomyelitis. ^,

Intracranial septic thrombophlebitis is mostly associated with sinus, mastoid, or facial infections ( S. pneumoniae, ^, S. pyogenes, or S. aureus) . Other otopathogens or non-group A streptococci are also reported. Anaerobes (e.g., Fusobacterium species ), while rare (most often associated with Lemierre disease), have been more frequent since 2005 and can have severe complications. Polymicrobial infections can occur. ^,

Epidemiology

Brain abscess is uncommon in developed countries (1 per 8.8 million population). Risks vary geographically, e.g., associated with chronic otitis media in China (60%) but less in Europe (30%). Peak age is 4–7 years among the 25% of brain abscesses occurring before 15 years of age. Neonatal brain abscesses are most frequently associated with gram-negative bacterial meningitis. In immunocompetent hosts, most brain abscesses are solitary, but are multiloculated in 10%–20%. Multiple abscesses most frequently follow hematogenous spread or occur in neonates or immune compromised patients.

Intracranial subdural empyema occurs predominantly in males (3:1) of teen years, but is sex neutral in young children, originating from paranasal sinus or middle ear/mastoid infection in about 85%, and hematogenously in 5%–10%. Intracranial subdural empyema after neurosurgical procedures (e.g., craniotomy) is infrequent (0.04%).

Spinal subdural abscess is rare in children; obesity is a possible risk factor. Spinal epidural abscess also is rare (<200 reported pediatric cases; ^, 6/100,000 hospital admissions). ^,

Intracranial epidural abscess is the most common CNS suppurative complication of oto-mastoid infection. Posterior fossa epidural abscesses originate from middle ear/mastoid infections after osseous erosion of the petrous pyramid or over the sigmoid sinus plate, from orbital abscesses or frontal sinusitis via valveless emissary veins, or concurrent with subdural empyema or cavernous sinus thrombosis. After neurosurgical procedures, epidural abscess is 10–40 times more frequent than subdural empyema but is uncommon (0.43%–1.8%).

Suppurative intracranial thrombophlebitis usually accompanies another intracranial infection, which usually is extradural, e.g., mastoiditis or paranasal sinusitis. However, 10%–20% originate from facial (typically the middle third) or dental infections. Otogenic-infection related cerebral venous thrombosis also has been reported.

Pathogenesis

Clinical Manifestations