Bacterial Infections of the CNS

Question 1

What are the major agents of infectious meningitis?

Answer 1

• Pnemococcus
• Group B Strep
• Meningococcus
• H. influenzae
• Syphilis
• Lyme
• TB
• Listeria
• Fungi
• Enterobacteriaceae
• Pseudomonas
• Viruses

Question 2

What are the classic symptoms of meningitis?

Answer 2

• headache
• fever
• photophobia
• stiff neck

Question 3

How does pediatric meningitis present?

Answer 3

• fever- cold hands and feet
• refusing food or vomiting
• fretful, dislike being handled
• pale blotchy skin
• blank, staring
• drowsy
• stiff neck
• high pitched

Question 4

What is the bacteriology of Neisseria meningitidis?

Answer 4

• gram neg Diplococci, facultative intracellular
• human restricted
• encapsulated
• 13 serotypes
• oxidase+
• catalyse+
• ferments glucose and maltose, NOT sucrose or lactose
• growth inhibited by trace metals and fatty acids use chocolate agar not blood agar

Question 5

What is the pathogenesis of N meningitidis?

Answer 5

• transmitted by airborne droplets
• colonize nasopharnyx (only reservoir)
• asymptomatic carrier, common in prisons, dorms, military, family of index case
• spread and colonization may be enhanced by concomitant upper respiratory viral infections
• infection often resolves without symptoms: IgG complement and neutrophils defend, leave lifelong immunity to infecting strain (individuals with def in C5-C9 predisposes spread to beyond resp system
• many have natural immunity by age 20; immune mothers passively immunize newborns
• most common 2-18 years of age
• colonize favorite sites once meningococcemia: joints (septic arthritis), meninges (fatal if untreated or leave damage with treatment)

Question 6

What are the virulence factors of N meningitidis?

Answer 6

• IgA Protease: cleaves IgA, reduces defense of mucus membrane
• Polysaccharide capsule: resists phagocytosis
• Endotoxin LOS (component of Gram neg cell wall, cause fever or shock)

Question 7

What does N. meningitidis look like on exam?

Answer 7

• 1/3 cases adult, 2/3 peds
• septic arthritis: joint pain- draw joint fluid
• meningitis: adults: classic fever, headache, stiff neck, progression to coma is bad
• young children: irritability, convulsions, lassitude, fever, abdominal discomfort/vomiting
  both: draw CSF (tap between L3 and L4), admit

Question 8

How does Meningococcemia look on exam?

Answer 8

• fever and hourly-spreading petehcnial skin rash (may be hard to see on dark skin; will eventually be followed by gangrene)
• rarely may be present for weeks before symptoms become alarming
• 5-15% develop Waterhouse-Friderichen syndrome: high fever, shock, widespread purpura, DIC, thrombocytopenia, destruction of adrenal glands (50% fatal)

Question 9

How does N. meningitidis look on labs?

Answer 9

• Septic arthritis: joint fluid: gram stain and culture on chocolate agar
• Meningitis: CSF: increased PMNs, Gram stain (50% sensitive) and culture on chocolate agar, Gram neg cocci in CSF smear, or latex agglutination test for capsule polysaccharide in CSF
• Meningococcemia: Blood- gram stain and culture on chocolate agar, set of tests for DIC
• PCR test (targets meningitidis specific DNA insertion sequence in blood buffy coat samples: no lumbar puncture!)

Question 10

How do you distinguish between N. meningitidis and N gonnorrhoeae?

Answer 10

• only meningococci ferments maltose

- alternatively theres IF

Question 11

How do you treat N. meningitidis?

Answer 11

• Penicillin G unless allergic or local history of drug resistance
• Alternatives: Ceftriaxone, cefotaxime, and cefuroxime; if severely allergic to penicillin, choloramphenicol
• Fulminant meningococcemia: admit to ICU, support circulation and renal function
• NO STEROIDS

Question 12

How can n. meningitidis be prevented?

Answer 12

• close contacts of index case got prophylatic rifampin, ceftriaxone, or ciprofloxacin (excreted efficiently into saliva)
• vaccines recommended for travelers (Mecca outbreaks), college/boarding school students, 11-12 year olds, not suitable for <2 years
• unconjugated= Menomune
• conjugated= Menactra

Question 13

What is the bacteriology of Group B strep?

Answer 13

• GBS- S. agalactiae
• encapsulated Gram positive cocci
• beta hemolytic
• polysaccharide toxin virulence factor
• pilus-like attachment virulence factor
• serotype specific antibody mediated immunity
• normal vaginal flora (15-45%) transmits to neonate shortly before and during delivery
• may also be normal flora in GI and upper resp tract
• very seldom causes disease in previously healthy adults; may cause bacteremia, cellulitis, UTI with predisposing factors

Question 14

Neonate GBS

Answer 14

• 1-2% of neonates of GBS mothers develop invasive disease
• most common cause of neonatal sepsis
• usually serotype 3 (of 10)
• Early disease: pneumonia with bacteremia, presents 1-7d postpartum, prevented by intrapartum IV antibiotics
• Late disease- bacteremia with meningitis, presents 1-12wk postpartum
• prematurity and prolonged rupture of membranes are risk factors

Question 15

What other group is effected by GBS?

Answer 15

• -may be seen in geriatric patients with diabetes, malignancy, CHF
• these rare infections seem to be becoming more common; probably both improved reporting and also population becoming older, more diabetic, more immunosuppressed

Question 16

What does GBS look like on exam?

Answer 16

• patients presents with pain, fever, other symptoms specific to site
• meningitis: spinal tap for gram+ cocci in pairs or short chains
• cellulitis, abscess: gram stain and culture of appropriate sample (tissue biopsy, aspirate)
• CT/MRI for deep abscesses
• echo for endocarditis

Question 17

What is the lab test of GBS?

Answer 17

• CAMP test: CAMP factor secreted by B group strep (and Listeria) enhances activity of Beta hemolysin from S aureus
• Hippurase/Hippurate Test: colorimetric test for hippurase, produced by GBS, Gardnerella vaginalis, Campylobacter jejuni, Listeria monocytogenes

Question 18

What is the treatment for GBS?

Answer 18

• IV penicillin or amoxicillin
• if allergic vancomycin
• surgical intervention may be needed: heart valve replacement for endocarditis, abscess removal for cellulitis, amputation for diabetic foot

Question 19

How do we prevent GBS?

Answer 19

• test term pregnant patients for GS by swab and culture. If positive:
• Intrapartum (during delivery) IV of penicillin or amoxicllin
• if allergic use clindamycin or erythromycin, but resistant strains exist
• strategy has reduced early disease in US over past decade, but there are questions about the sensitivity of the culture and PCR tests

Question 20

What is the bacteriology of Pneumococcus?

Answer 20

• Strep penumonaiae
• gram+, catalase-, facultative anaerobe
• in culture, form diplococci in chains
• pathogenic strains are encapsulated
• the most common cause of community acquired pneumonia, bacterial meningitis, bacteremia, and otitis media as well as an important cause of sinusitis, septic arthritis, osteomyelitis, peritonitis, and endocarditis
• a major childhood pathogen worldwide with deaths from pneumonia and meningitis

Question 21

What is the pathogeneis of Pneumococcus?

Answer 21

• easily colonize upper resp tract using adhesion virulence factors (20-50% carriage rates in general population)
• infections peak in Fall and Winter, when carrier congregate more closely
• in healthy adults and older children, contained by innate immunity
• in young children, or in patients with preexisting asthma, allergies, bronchitis, smoking, COPD, bacteria can spread

Question 22

What are the two ways Pneumococcus can spread?

Answer 22

• Direct extension: sinuses, eustachian tubes, bronchi
• Hematogenous spread: blood joint fluid, peritoneum, CSF
• capsule protects bacterium against phagocytosis and classic complement unless anti-capsule IgG present
• pathogenic strains produce pneumolysin, some produce hemolysin, neuraminidase, hyaluronidase, but exact contribution of these exotoxins to pathogenesis is unclear
• infection raises a strong inflammatory response, which underlies most of the clinical disease symptoms

Question 23

What does Pneumococcus look like on exam (direct extension)?

Answer 23

• diseases of direct extension (non-invasive)- sinusitis, otitis media, bronchitis, pneumonia
• pneumonia causes significant morbidity and mortality (10-20%)
• patient looks ill, anxious
• predispositions: asthma, COPD, chronic bronchitis, smoking or frequent exposure to cigarette smoke
• can hear rales in most patients dullness to percussion in half
• on radiology: adolescents and adult- lobar consolidation; infants and young children: scattered parenchemyal consolidation, bronchopneumonia

Question 24

What does Pneumococcus look like on exam (hematogenous spread)?

Answer 24

• meningitis, septic arthritis, pericarditis, endocarditis, osteomyelitis
• bimodal distribution, younger than 5 older than 65, also anyone immunosuppresed
• meningitis develops over hours or days, neurologic signs are often prominent (admit for antibiotics and MRI)
• mental status changes
• lethargy
• delirium
• Brudzinski(+)
• cranial nerve palsies
• focal neurologic defects

Question 25

How does Pneumococcus look on lab?

Answer 25

-non-invasive disease: can usually be treated based on exam, optional Gram stain

• Invasive: gram stain and culture of appropriate samples (blood, sputum, CSP, abscess aspirates or biopsies). Blood cultures usually positive
• begin antibiotic sensitivity testing
• urine antigen testing is available, useful for pneumonia in young children who don’t produce enough sputum for testing

Question 26

What meningitis spinal tap findings are typical of bacterial meningitis?

Answer 26

• elevated opening pressure
• elevated WBC count and neutrophil level
• elevated protein
• decreased glucose
• highly elevated lactic acid
• gram stain and culture are positive unless antibiotic treatment began > 4 hours prior to tap

Question 27

How to treat non-invasive pneumococcus?

Answer 27

• anything less than severe pneumonia: proceed with treatment using antibiotics that include S. pneumoniae among other probably causes: amoxicillin or cephalosporin for everybody, fluoroquinolones or doxycycline for adults- only, outpatients
• severe pneumonia: admit, vancomycin becomes another antibiotic option

Question 28

How to treat invasive pneumonoccous?

Answer 28

• admit patient, take samples, start antibiotics, start cultures, perform antibiotic susceptibilty testing on cultures
• initial antibiotics are vancomycin plus ceftriaxome or cefotaxime
• if isolate testing comes back resistant, add rifampin, meropenem, or chloramphenical
• steroids may be used with caution in addition to antibiotics, early in the antibiotics course
• cellulitis and septic arthritis may require surgical care in addition to antibiotics

Question 29

What are the positives and negatives of pneumococcal antibiotic resistance?

Answer 29

• conferred by mutations changing the bacterial cell wall sites to which the antibiotics bind such that the binding affinity is lowered
• consequently, an increase in dosage can sometimes overcome resistance for this pathogen. MIC (minimum inhibitory concentration) describes the dosage necessary to kill the patient’s isolate
• but it is carried on a transposon that includes resistance genes for multiple antibiotics, so if theres resistance to any, probably many

Question 30

How do you prevent pneumonoccous prevention?

Answer 30

• Prevnar7 vaccine raises protective IgG against the capsules of the seven serotypes that most commonly caused invasive disease prior to 2000
• Universal childhood vaccination with Prevnar7 starting in 2000 knocked down levels of invasive disease 90%
• childhood causes of invasive diseased caused by those serotypes essentially disappeared (more effective than anyone expected)
• rates of carriage of those serotypes dropped as herd immunity was achieved
• rates of disease caused by other serotypes of pneumococcus increased (“replacement disease”
• Prevnar13 vaccine, providing coverage for original seven plus 6 of the newly problematic serotypes is now available; may be used for childhood vaccination series, may be given as a booster to those who received Prevnar7 series