Microbiology of CNS Infections I: Meningitis March 29, 2010 1.

Review the unique anatomy of the brain, spinal cord, and BBB and understand how infectious organisms attack these structures. a. Brain/Spinal Cord: i.

ii. *Infection can occur during trauma (e.g. skull fractures) or procedures (e.g. craniotomy) = DIRECT TRANSFER b. BBB: i. Formed by tight junctions between cells of the cerebral capillaries, choroid plexus, and arachnoid meninges prevents macromolecules from entering the brain parenchyma ii. BBB blocks marcomolecules, microorganisms, most immunocompetent cells, and antibodies from passing

iii.

iv. *Disruption of CNS allows Abs to leak passively into the CNS along with other serum proteins (i.e. protein levels increases) 2. Understand how bacterial, viral, and fungal infections of the blood can lead to meningitis. a. *Most bacteria and viruses proliferate in blood and then invade the CNS i. Bacteria that stay as bacteremia have capsid polysaccharides that increase their resistance to phagocytosis ii. Viruses are small and hard to clear 1. Some infect endothelial cells or choroid plexus epithelium and then enter the CNS 2. Mumps: choroid plexus cells have viral nucleocapsids b. Bacteria i. Direct transfer (e.g. skull fractures) ii. Axoplasmic transport (into the CNS or within the CNS along axons) 1. Tetanus: sequestered in vesicles at peripheral axon terminals and carried to the cell body within the CNS iii. Hematogenous spread c. Viruses i. Use of neuronal surface receptors ii. Axoplasmic transport

1. Rabies: moved within the axon transport system iii. Hematogenous iv. Olfactory d. Fungal i. Olfactory ii. Hematogenous 3. Know the major bacteria, viruses, and fungi that cause meningitis a. Bacteria i. Direct transfer: 1. Craniotomy/skull fracture: Staph aureus and Enterobacteriaceae 2. Surgical shunt: Staph epidermidis ii. Axon transport: Tetanus iii. Hematogenous: *H. influenzae, *Staph pneumonia, *Neisseria meningitides, TB, Rickettsiae b. Viruses i. Axon transport: Rabies, Herpesvirus simiae ii. Hematogenous: *Enteroviruses, arbovirus, mumps virus, HIV c. Fungi i. Olfactory: Naegleria fowleri ii. Hematogenous: Cryptococci, Coccidioides 4. Understand the utility of sampling the CSF to detect organisms that cause meningitis a. Can differentiate between CNS infections by testing the CSF! Agent
Bacterial (acute) Subacute Viral

Pressure
N/high N N

Type of cells
PMN Mononuclear Mononculear

Protein
Very high Very high High

Sugar
Very low N/low N

Culture
Very positive Positive Special tests

5. Know the properties of the bacteria infecting the CNS, tests used to detect them, and antibiotics used to treat bacterial infections of CNS Group
Neonates <28 days old Adults Subacute

Bacteria responsible
Enteric bacteria (E. coli), group B strep, or Listeria Neisseria meningitides, Strep pneumoniae TB

Other
50% of meningitis deaths Neisseria: epidemic disease Others: sporadic disease Slower progression

a. Can test by demonstrating bacterial antigens b. Tx i. Vaccine: reduced meningitis due to H. influenza ii. Antibiotics: penicillin G, ampicillin, vancomycin, 3rd generation cephalosporin 1. Infants <3 mo old = ampicillin 6. Know the important fungal infections of the CNS, the fungi that cause them, and how to treat them. a. Subacute meningitis: Cryptococcus i. Can be identified by mixing India ink with CSF to outline capsule of the organisms and differentiate from mononuclear inflammatory cells 1. On stain: organisms will have clear halo surrounding them b. Treat with fungal antibiotics depending on the fungal strain and susceptibility 7. Know the important viruses that infect the CNS and their effects. a. Enteroviruses (40%), unknown (30%), mumps (15%) b. Treatment: i. Disease is benign and self-limited only need symptomatic treatment 8. Clinical Manifestations of Meningitis a. Headache, fever, and nuchal rigidity (stiffness of neck in passive forward flexion) b. Brudzinski sign: flexion of the neck + reflex flexion of the legs c. Kernig sign: limited extension of the leg at the knee

d. Obtundation: reduced consciousness e. Rash (enterovirus) f. Parotitis (mumps) g. Petechiae: meningococcemia