Bacterial Infections of the CNS Flashcards
1
Q
What are the major agents of infectious meningitis?
A
- Pnemococcus
- Group B Strep
- Meningococcus
- H. influenzae
- Syphilis
- Lyme
- TB
- Listeria
- Fungi
- Enterobacteriaceae
- Pseudomonas
- Viruses
2
Q
What are the classic symptoms of meningitis?
A
- headache
- fever
- photophobia
- stiff neck
3
Q
How does pediatric meningitis present?
A
- fever- cold hands and feet
- refusing food or vomiting
- fretful, dislike being handled
- pale blotchy skin
- blank, staring
- drowsy
- stiff neck
- high pitched
4
Q
What is the bacteriology of Neisseria meningitidis?
A
- 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
5
Q
What is the pathogenesis of N meningitidis?
A
- 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)
6
Q
What are the virulence factors of N meningitidis?
A
- 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)
7
Q
What does N. meningitidis look like on exam?
A
- 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
8
Q
How does Meningococcemia look on exam?
A
- 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)
9
Q
How does N. meningitidis look on labs?
A
- 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!)
10
Q
How do you distinguish between N. meningitidis and N gonnorrhoeae?
A
- only meningococci ferments maltose
- alternatively theres IF
11
Q
How do you treat N. meningitidis?
A
- 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
12
Q
How can n. meningitidis be prevented?
A
- 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
13
Q
What is the bacteriology of Group B strep?
A
- 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
14
Q
Neonate GBS
A
- 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
15
Q
What other group is effected by GBS?
A
- -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
16
Q
What does GBS look like on exam?
A
- 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
17
Q
What is the lab test of GBS?
A
- 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
18
Q
What is the treatment for GBS?
A
- 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
19
Q
How do we prevent GBS?
A
- 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
20
Q
What is the bacteriology of Pneumococcus?
A
- 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
21
Q
What is the pathogeneis of Pneumococcus?
A
- 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
22
Q
What are the two ways Pneumococcus can spread?
A
- 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
23
Q
What does Pneumococcus look like on exam (direct extension)?
A
- 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
24
Q
What does Pneumococcus look like on exam (hematogenous spread)?
A
- 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
25
How does Pneumococcus look on lab?
-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
26
What meningitis spinal tap findings are typical of bacterial meningitis?
- 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
27
How to treat non-invasive pneumococcus?
- 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
28
How to treat invasive pneumonoccous?
- 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
29
What are the positives and negatives of pneumococcal antibiotic resistance?
- 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
30
How do you prevent pneumonoccous prevention?
- 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
