CNS infection

Question 1

Symptoms of Meningitis

Answer 1

headache
stiff neck
fever
photophobia

Question 2

Symptoms of meningitis in peds

Answer 2

fever - cold hands & feet
refusing food/vomiting
pale blotchy skin
blank staring
stiff neck

Question 3

Neisseria meningitidis

• Gram (), shape, where do you find it?
• what organism fo you find it on?
• Encapsulated?
• How many serotypes?
• Oxidase? Catalase?
• What does it ferment?
• What is growth inhibited by?

Answer 3

• Gram negative diplococci, facultative intracellular
• human-restricted
• encapsulated (nonencapsulated strains are nonpathogenic)
• 13 serotypes
• oxidase-positive, catalase positive
• ferments glucose and maltose, not sucrose or lactose
• growth inhibited by trace metals and fatty acids: chocolate agar, not blood agar

Question 4

How is N. medingitidis transmitted?

Where does it colonize?

How do most infections present?

Answer 4

Airborn droplets

colonizes the nasopharynx (only reservoir) -> asymptomatic carrier, common in prisons, dorms, military, family of index case

Most infections resolve without symptoms: IgG-enhanced complement and neutrophils defend, leave lifelong immunity to infecting strain

Many individuals have some natural immunity by age 20; immune mothers passively immunize newborns

Question 5

N. meningitidis pathogenesis

What happens if it enters the bloodstream?

Answer 5

Meningococcemia - colonizes favorite sites - joints (septic arthritis), meninges (meningitis, fatal if untreated, with treatment, may kill or leave damage)

May cause epidemics of meningitis

Most common cause in 2-18 yr age range

Together with Strep pneumoniae, causes >80% postinfant bacterial meningitis

Question 6

N. meningitidis virulence factors

Answer 6

IgA protease: cleaves IgA, reduces defense of mucus membrane

Polysaccharide capsule (resists phagocytosis)

Endotoxin LOS (component of Gram (-) cell wall, causes fever, shock) - LOS is lower molecular weight

Question 7

Is there a vaccine for N. meningitidis?

Answer 7

Ab to capsule is protective -> vaccine

deficiency inlate-acting complement components (c5-C9) is predisposing for complications

Question 8

N. meningitidis diagnosis

Answer 8

1/3 cases adult, 2/3 pediatric

septic arthritis: joint pain-draw joint fluid

meningitis: Adults = classic fever, headache, stiff neck, progression to coma

young children: irritability, convulsions, lassitude, fever, abdominal discomfort, vomiting

BOTH DRAW CSF and ADMIT

Question 9

Meningococcemia

Answer 9

Fever and hourly-spreding petechial skin rash (may be hard to see on dark skin) - draw blood and CSF, admit to ICU

Rarely may be present for weeks before symptoms become alarming (“chronic’)

5-15% develops 50% fatal Waterhouse-Friderichen syndrome: High fever, shock, widespread purpura, disseminated intravascular coagulation (DIC), thrombocytopenia, destruction of adrenal glands

Question 10

N. meningitidis lab:

septic arthritis:

Meningitis:

Meningococcemia:

Answer 10

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 (-) cocci in CSF smear suffice for diagnosis, alternatively, latex agglutination test for capsule polysaccharide in CSF

Meningococcemia: Blood: gram stain and culture on chocolate agar. set of tests for DIC

Question 11

N. meningitidis diagnosis: Lab

Answer 11

PCR testing gives simultaneous rapid results for many patients and sample types

PCR test targets meingitidis-specific DNA insertion sequence in blood buffy coat samples: no lumbar puncture.

differentiating N. meningitidis from N. gonnorrhoeae: only meningococci ferment maltose

Question 12

How to treat N. meningitidis

Answer 12

Penicillin G unless allergic, or local history of drug resistance

Alternates: Ceftriaxone, cefotaxime, and cefuroxime; if severely allergic to penicillin, chloramphenicol

Fulminant meningococcemia: admit to ICU, support circulation and renal function

Prescribing glucocorticosteroids for the rash and arthritis bad, even though they are recommended for other types of meningitis

Question 13

How to prevent N. meningitidis

Answer 13

Close contacts of index case get prophylactic rifampin, ceftriaxone, or ciprofloxacin (excreted efficiently into saliva)

Vaccines recommended for travels (Mecca outbreaks), college/boarding school students, 11-12 yrs (not suitable for < 2 yrs)

Question 14

GBS: Bacteriology

gram (), shape, encapsulated?

Beta hemolytic?

Two virulence factors

Answer 14

S. agalactiae

encapsulated gram(+) cocci

beta hemolytic

polysaccharide toxin virulence factor

Pilus-like attachment virulence factor

serotype-specific antibody-mediated immunity

Normal vaginal flora transmits to neonate shortly before and during delivery

may also be normal flora in GI and upper respiratory tract

Question 15

GBS risk group 1 pathogenesis

Answer 15

neonates of GBS+ mothers develop invasive disease

Most common cause of neonatal sepsis

Usually serotype 3 (of 10)

2 types:
early disease
pneumonia w/bacteremia
presents with 1-7d postpartum
prevented by intrapartum IV antibiotics

Late disease
bacteremia with meningitis
presents 1/12wk postpartum

Question 16

GBS risk group 2 of 2

Answer 16

geriatric with predispositions
diabetes, malignancy, congestive heart failure

rare infections seem to be becoming more common; probably both improved reporting and older population, more diabetic and more immunosuppressed

Question 17

GBS exam

Answer 17

Patient 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

Echocardiogram for endocarditis

CAMP test: CAMP factor secreted by group B strep (and listeria) enhances activity of beta hemolysin form S. aureus

Hippurase/Hippurate test: Colorimetric test for hippurase, produced by GBS, Gardnerella vaginalis, Campylobacter jejuni, Listeria monocytogenes

Question 18

GBS: Treatment

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

Pneumococcus
Species
Gram (), catalase?, where is it foun?
Morphology?
Capsule?

Answer 19

Strep pneumoniae

Gram (+), catalase (-), faculative anaerobe

In culture, form diplococci in chains

Pathogenic strains are encapsulated

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 20

Pneumococcus pathogenesis

Answer 20

Ealisy colonizes upper respiratory tract using adhesion virulence factors (20-50% carrier rates in pop.)

infections peak in Fall and Winter when carriers congregate more closely

in healthy adults and older children, contained by innate immunity

in young children, or in patients with pre-existing asthma, allergies, bronchitis, smoking, COPD, bacteria can spread

Question 21

Two types of pneumococcal disease

Answer 21

1. Direct extension: sinuses, eustachian tubes, bronchi
2. Hematogenous spread: blood, joint fluid, peritoneum, CSF

Capsule protects bacterium against phagocytosis and classic complement unless anti-capsule IgG is already present (protective)

Pathogenic strains all produce pneumolysin, some also produce hemolysin, neuraminidage, 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 22

Pneumococcus exam

Diseases of direct extension (Non-invasive disease):
Sinusitis, otitis media, bronchitis, pneumonia

PNEUMONIA ->

Answer 22

pneumonia causes significant morbidity and mortality (10-20%)

patient looks ill, anxious

predispositions: asthma, COPD, chronic bronchitis, smoking or frequent exposure to cigarette smoke
stethoscope: can hear rales in most patients, dullness to percussion in half

radiology findings:
adolescents and adults: lobar consolidation
infants and young children: scattered parenchymal consolidation, bronchopneumonia

Question 23

Pneumococcus: Exam

Diseases of hematogenous spread (invasive disease): Meningitis, septic arthritis, pericarditis, endocarditia, osteomyelitis

Answer 23

bimodal distribution: patients younger than 5 or older than 65

Anyone who is immunosuppressed

meningitis develops over hours or days, neurologic signs often prominent, admit for antibiotic and MRI

• mental status changes
• lethargy
• delitium
• brudzinski(+)
• cranial nerve palsies
• focal neurologic defects

Question 24

Pneumococcus: Lab

Non-invasive disease

Invasive disease

Answer 24

Non-invasive: can usually be treated based on exam, optional gram stain

invasive disease: gram stain and culture of appropriate samples (blood, sputum, CSF, 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 25

Meningitis spinal tap findings are typical of bacterial meningitis

Answer 25

• elevated opening pressure
• elevated WBC count and neutrophil level
• decreased glucose
• highly elevated lactic acid
• gram stain and culture are positive unless antibiotic treatment began >4hr b4 tap

Question 26

Pneumococcus treatment

noninvasive disease

Answer 26

anything less than severe pneumonia: proceed with treatment using antibiotics that include S. pneumoniae among other probable causes: amoxicillin or cephalosporin for everyone, fluoroquinolones or doxycycline for adults-only, outpatient

severe pneumonia: admit, vancomycin becomes another antibiotic option

Question 27

Pneumococcus treatment for invasive disease

Answer 27

admit patient, take samples, start antibiotics, start cultures, perform antibiotic susceptibility testing on cultures

initial antibiotics are vancomyvin plus ceftriazone and cefotaxime

if isolate testing comes back resistant, add rifampin, meropenem, or chloramphenicol

steroids may be used with caution in addition to antibiotics, early in the antibiotic course

cellulitis and septic arthritis may require surgical care in addition to antibiotics

Question 28

Pneumococcal antibiotic resistance

Answer 28

conferred by mutations changing the bacterial cell wall sites to which the antibiotics bind such that 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

The resistance is carried on a transposon that includes resistance genes for multiple antibiotics, so if there is resistance to any, there is resistance to many

Question 29

Pneumococcus prevention

Answer 29

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 cases of invasive disease 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 the 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 the prevnar 7 series