Encapsulated
Gram-positive diplococci or short chains; Oval or lancet-shaped
cells (0.5-1.2um) (see WebLinked
image; see WebLinked
image; see WebLinked image)
Capsular
antigen in virulent strains: Complex polysaccharide; Cross reactive
Gram
positive but stain poorly and may appear gram negative
Enriched
media with 5% defibrinated blood (provides catalase)
Increased
carbon dioxide for 5-10% of strains (capnophilic)
Ferment
carbohydrates; Major endproduct is lactic acid; High concentrations of
glucose in medium is inhibitory as lactic acid levels become toxic (like
Grp A streptococci)
Choline
requirement (phosphocholine in cell wall is unique to S. pneumoniae)
for cell wall hydrolysis; Amidase (autolytic enzyme) inactive without
choline and cell division stops
Catalase
negative (unlike staphylococci); Accumulation of hydrogen peroxide inhibits
growth; Exogenous source of catalase needed for growth (e.g., blood)
Two
forms of teichoic acid polymer (galactosamine and phosphocholine)
in cell wall
Cell
surface exposed (C-substance): Precipitates a serum globulin fraction
known as C-reactive protein (CRP) in the presence of calcium
CLINICAL SYNDROMES:
Remains
a leading cause of morbidity and mortality
Radiological
resolution (clean chest X-ray) within 2-3 weeks with antimicrobial therapy
Bacterial
Sinusitis (paranasal sinuses)
Often
antecedent upper respiratory tract viral infection with PMN obstruction
of sinuses and ear canal
All
age groups
Otitis
Media (middle ear inflammation):
Often
antecedent upper respiratory tract viral infection with PMN obstruction
of sinuses and ear canal
Primarily
in young children
Meningitis:
CNS (central nervous system) involvement after bacteremia, sinusitis or
otitis media, head trauma
Primarily
in pediatric population
Mortality
and severe neurological complications are 4-20 times more likely than
with meningitis caused by other organisms
Bacteremia:
25-30%
with pneumonia
80%
with meningitis
Endocarditis
possible
EPIDEMIOLOGY:
Colonizes
oropharynx and/or nasopharynx; Spreads to normally sterile site
Stimulates
local inflammatory response, but evades phagocytic killing
Carriers
(5-75% Incidence): Transient colonization of throat and nasopharynx
by a succession of different serotypes; Duration decreases with each
successive serotype (serotype-specific immunity); Disease generally from
newly acquired strain
Serious
disease most commonly in young children or elderly adults
Often
preceded by (antecedent) respiratory viral infection (e.g.,
influenza, measles)
Conditions
interfering with normal clearance of bacteria predisposes host to pneumococcal
infections
Chronic
pulmonary disease
Alcoholism
Congestive
heart failure
Diabetes
mellitus
Chronic
kidney disease
Splenic
dysfunction or splenectomy: Decrease in clearance from blood and defective
early antibody production
PATHOGENESIS AND IMMUNITY:
Pathogenesis
primarily due to host response to infection
Three
Classes of Virulence Factors:
Colonization and migration
(spreading)
Tissue destruction
Phagocytic survival
Cellular
components:
Complex
polysaccharide capsule: Antiphagocytic
Encapsulated
(smooth) strains are virulent
Nonencapsulated
(rough) strains are avirulent
Type-specific
anticapsular antibodies are protective
Capsular
polysaccharides are soluble (a.k.a., specific soluble substances) and
free polysaccharides can bind opsonins and further inhibit phagocytosis
Protein
adhesin: Binds to oropharyngeal epithelium enabling initial colonization
Teichoic
acid: Activate alternative complement pathway; C5a production mediates
inflammation
Peptidoglycan
fragments: Activate alternative complement pathway; C5a production mediates
inflammation
Phosphorylcholine:
Mediates tissue destruction, spreading, and protection from opsonization
and phagocytosis; Binds to host cell receptors for platelet-activating
factor allowing entrance into cells
Biochemically
similar to Streptolysin O (O2 labile)
Assists
spreading by destroying ciliated epithelial cells by binding cholesterol
in host cell membranes and causing pore formation
Tissue
destruction mediated by activation of classic complement pathway; C3a
and C5a production with activated leukocytes producing cytokines (e.g.,
IL-1, TNF-alpha) which result in enhanced inflammatory cell response,
fever, tissue damage, etc.
Inhibits
phagocytic killing by suppressing oxidative burst
Secretory
IgA protease: Assists spreading by enzymatically disrupting secretory
IgA (sIgA) clearance of bacteria
Artificially
acquired immunity: Immunization via polyvalent vaccine prophylaxis
Purified
capsular material from most common serotypes (23 different
polysaccharides covering 94% of clinically relevant serotypes);
Until recently this formulation was not effective in young children
or elderly adults or in other high risk groups
In
1999, a vaccine formulation was shown to be effective and has
been approved by the FDA for use against otitis media in young children
LABORATORY IDENTIFICATION:
Quellung
(capsular precipitation; swelling) reaction: Anticapsular antibodies
cause an increase in refractivity of the capsule making it readily apparent
by microscopy
Susceptibility
to optochin (ethylhydrocupriene dihydrochloride)
Soluble
in bile: Colonies dissolve when exposed to drop of bile (differentiates
from alpha-hemolytic streptococci and Enterococcus); Autolysis after
bile activation of autolysins; Also performed in broth culture with clearing
TREATMENT:
Drug
of Choice: Penicillin; Alternates: Cephalosporins, erythromycin, chloramphenicol
(meningitis); Resistant to tetracycline
Multiple
Antibiotic Resistance (Multidrug Resistance): Recognized in 1977;
Including low level resistance to penicillin
Dramatic
increase in frequency of moderate resistance and in the emergence of high
levels of resistance (High level resistance: MIC > 2.0 ug/ml)