Meningitis Flashcards
Clinical symptoms of meningitis
Fever (not as likely in elderly), headache. Also: nuchal rigidity, photophobia, rash, upper respiratory symptoms, nausea, anorexia, vomiting, diarrhea, altered mental state
Location of meningitis
Subarachnoid space
What does the subarachnoid space lack?
Antibody and complement production needed for phagocytosis
Infectious agents associated with meningitis
- viral 2. bacteria 3. fungi 4. mycobacteria. 5. protozoa
Bacterial meningitis lumbar puncture findings
Increased intracranial pressure. Very increased WBC count. Mostly PMN. Very increased proteins. Decreased glucose.
Viral meningitis lumbar puncture findings
No increased intracranial pressure. Increased WBC count. Mostly lymphocytes, about 20% PMNs. Increased protein. Glucose levels about the same
Fungal meningitis lumbar puncture findings
Increased intracranial pressure. Increased WBC count (more than viral) Mostly lymphocytes. Increased protein. Glucose about the same
TB meningitis lumbar puncture findings
No increased intracranial pressure. Increased WBC count (less than bacterial). Mostly lymphocytes. Increased protein and decreased glucose.
Aseptic Meningitis syndrome
- Often viral, could be noninfectious though.
- Fever, headache, photophobia, less neck stiffness and altered mental state.
- Slight increase in protein, glucose normal. Increase in lymphocytes and monocytes.
- Highest incidence in 1st yr of life.
- Supportive therapy. Recover on own
- Can be fatal in neonates
What are more than 855 of viral meningitis types associated with?
Enteroviruses
Do enteroviruses include RNA or DNA viruses?
Usually RNA viruses
When are enteroviruses more common?
Summer and fall
Enterovirus/Picornavirus characteristics
- Transmitted oral/fecal or respiratory.
- ssRNA (+)
- Icosahedral
- No envelope
Bacterial (Septic) meningitis
- Fever, stiff neck, irritability, neuro dysfunction.
- Acute onset and progression
- life-threatening
- Need prompt empiric therapy BEFORE lumbar puncture
- Inflammation associated with exudate in CSF
- Increased PMN, increased protein, decreased glucose
Bacterial meningitis treatment
Immediate empiric treatment with 3rd gen. cephalosporin (Ceftriaxone). Risk of other agents: vanco (MRSA), acyclovir (HSV-2), cefepime (pseudomonas), ampicillin (listeria). Even 3 hr delay in treatment can increase risk of fatality within 3 months. Consider prophylactic treatment of household and others exposed to oral secretions.
Most common causes of bacterial meningitis?
Streptococcus pneumonia
Neisseria meningiditis
Haemophilus influenza type b
Most common bacterial meningitis in adults?
Streptococcus pneumonia
Most common bacterial meningitis in children ages 11-16
Neisseria meningiditis
What should all adults over 65 be getting to protect against pneumococcal form?
13 valent pneumococcal conjugate vaccine
Steps in development of bacterial meningitis?
- mucosal colonization at nasopharynx
- invasion and multiplication in bloodstream
- cross bbb
- egress into CSF
- Release inflammatory cytokines in CSF by astrocytes and microglia
- Increased permeability of bbb
- Diapedisis of leukocytes in CSF
- Edema and increased intracranial pressure.
- Neuronal injury including hearing loss (CN VIII)
Gram - organisms causing bacterial meningitis?
Neisseria meningitidis and Haemophilus influenzae
Gram + organism causing bacterial meningitis?
Streptococcus pneumoniae
Lipopolysaccharide (LPS)/endotoxin
Endotoxin shed from gram - bacteria. Activates macrophages and causes release of NO (hypotension and shock) and IL-1 (fever).
Lipooligosacchride (LOS)
Neisseria meningitides structure (similar to LPS). Mimics brain sphingolipids so it is recognized as self
If skin rash present what forms of bacterial meningitis should you be leaning toward?
Neisseria meningitidis or haemophilus influenzae
When does meningitis occur?
When pathogen virulence factors overwhelm host defense mechanisms
Other virulence factors involved in bacterial meningitis?
Pili, IgA protease, Capsule composed of acidic polysaccharides
Pili virulence factor function
Colonization of the nasopharynx
IgA protease virulence factor function
Cleaves IgA allowing for colonization of mucosa
Capsule virulence factor function
Protects from phagocytosis of polymorphonuclear granulocytes
Neisseria meningiditis
Gram negative. Diplococcus.
Meningococcal meningitis (neisseria meningiditis) vaccine
covers 4 of the 13 serogroups
Meningococcal meningitis (neisseria meningiditis) virulence factors
pili, IgA protease, capsule, endotoxin
Meningococcal meningitis (neisseria meningiditis) outbreaks
More common in the winter and early spring (overcrowding). Transmitted through respiratory droplets
Meningococcal meningitis (neisseria meningiditis) treatment
Definitive and prophylactic treatment with ceftriaxone
Meningococcal meningitis (neisseria meningiditis) LOS virulence factor causes what symtms
Leads to thrombocytopenia. Disseminate intravascular coagulation–>hemorrhagic skin rash.
Streptococcus pneumonia–Pneumococcal meningitis
Gram + diplococci, lancet shape. Not in long chains
Streptococcus pneumonia–Pneumococcal meningitis transmission
Respiratory droplets. Meningitis is secondary to otitis media or paranasal sinusitis
Streptococcus pneumonia–Pneumococcal meningitis most common cases
Indivduals over 2 mths
Streptococcus pneumonia–Pneumococcal meningitis. What is used to identify the serotype?
Quellung (capsula swelling in response to specific anticapsular antiserum
Streptococcus pneumonia–Pneumococcal meningitis. Risks if on previous antibiotic?
Higher chance of resistant strain (can predict based on serotype). 19A esp. resistant. Would treat with vanco
Streptococcus pneumonia–Pneumococcal meningitis vaccine
Hepatovalent protein-conjugate
Haemophilis influenzae type B
Gram -, coccoid rod. Separate from the influenza virus
Haemophilis influenzae type B virulence factors
pili, outer membrane proteins, IgA protease and endotoxin
Haemophilis influenzae type B infection can be followed by what?
Hearing loss
Haemophilis influenzae type B most common age group?
Unvaccinated infants and young children
Haemophilis influenzae type B prevention
Hib vaccine–B capsular polysaccharide
Haemophilis influenzae type B growth support needed?
Chocolate agar with factors V (NAD+) and X (Hematin)
Torch infections (perinatal)
- mild maternal morbidity, can have major fetal consequences.
- meningitis, group B strep, E. coli, listeria.
- TORCH includes: toxoplasmosis, syphilis, varicella-zoster, parvo, rubella, CMV, HSV-2
Group B streptococcus (Streptococcus agalactiae)
- Normal part of GI and GU tract
- Vertical transmission to infant can occur
- Adult disease in immunocompromised increasing
- Sepsis, pneumonia, meningitis
- 2x as common in African American infants
- Pregnant women screened. Given penicillin G if carriers.
Group B streptococcus (Streptococcus agalactiae) classifcation
Bacitracin resistant, catalase negative, CAMP reaction (hemolysis of RBCs by phospholipase of GBS and B-hemolysin of S. aureus
E. coli K1 strains
- Gram negative rod
- enteric organism, bacteremia, and transcellular permeation of BBB
- LPS
- capsular polysaccharide prevents lysosome fusion
- May need to add carbapenem with ceftriaxone for empiric coverage
Most common chronic meningitis causes
Spriochetes (sypillis leptospira, borrelia burgdoreferi, treponema pallidium). Mycobacterium tuberculosis. Fungi (Cryptococcus neoformans, coccidioides and candida. More common in immunocompromised
Mycobacterium tuberculosis
- 25% cases have meningeal involvement.
- Gradual onset. Starts with generalized illness
- mostly 0-4 yr olds effected if in areas with high TB.
- In areas with low TB rates, mostly adults
- Acid-fast bacilli stain needed
Mycobacterium tuberculosis treatment
Rifampin, Isoniazid, pyrazinamide, ethambutol. BCG vaccine
Rifampin mechanism of action
Inhibits DNA dependent RNA polymerase. Induces formation of drug-metabolizing enzyme (including cytochrome P450)
Isoniazid mechanism
Inhibits mycolic acid (component of the mycobacterial cell wall).
Pyrazinamide mechanism
Unknown
Ethambutol mechanism
Inhibits cell wall synthesis by binding arabinosyl transferase
Cryptococcus neoformans
Inhaled as spores, can disseminate hematogenously to CNS in immunocompromised.
Cryptococcus neoformans treatment
Liposomal amphotericin B + flucytosine until culture negative, followed by fluconazole for 3-12 mths, sometimes for life
Amphotericin B Mechanism
Binds ergosterol creating holes in fungi membrane allowing leakage of electrolytes
Amphotericin B Spectrum
Broad. Invasive systemic fungal infections in immunocompromised. Active against yeast and molds
Amphotericin B distribution
Liposomal form can cross BBB
Amphotericin B adverse effects
TOXIC. Binds cholesterol. Decreases renal blood flow and can cause permanent destruction of the basement membrane
Amphotericin B resistance
Rare, decrease ergosterol in membrane
Flucytosine (5-FC) mechanism
Nucleic acid synthesis inhibitor. Antimetabolite selectively taken up and converted to 5-FU in fungi. Interferes with DNA and RNA synthesis
Flucytosine (5-FC) spectrum
Narrow. Only yeast! Not molds or dimorphic. Candida albicans and cryptococcus
Flucytosine (5-FC) distribution
Oral. Penetrates CNS
Flucytosine (5-FC) toxicity
Bone marrow suppression
Flucytosine (5-FC) Resistance
Loss of converting enzymes or transporters, cotreat with amphotericin B to min. development of resistance and increase uptake
Azoles (fluconazole (CNS), Itraconazole, voriconazole (CNS)) mechanism
Binds fungal P-450 enzyme and blocks production of ergosterol
Azoles (fluconazole (CNS), Itraconazole, voriconazole (CNS)) spectrum
Systemic mycoses (dimorphic fungi) and yeast
Azoles (fluconazole (CNS), Itraconazole, voriconazole (CNS)) distribution
Orally available, substrate for efflux pump in brain
Azoles (fluconazole (CNS), Itraconazole, voriconazole (CNS)) toxicity
Drug-drug interaction, hepatotoxicity, neurotoxicity, alters hormone synthesis. Avoid during pregnancy
Azoles (fluconazole (CNS), Itraconazole, voriconazole (CNS)) resistance
Altered cytochrome p450, upregulation of efflux transporters
