Streptococcus pneumoniae

Diseases Caused by S. pneumoniae

pneumonia

bacteremia

meningitis

infections of upper respiratory tract: otitis and sinusitis

Characteristics

Morphology:

Gram (+) lancet-shaped cocci (oval with somewhat pointed ends) arranged in pairs (diplococci) or short chains
on agar: encapsulated, dome shaped, mucoid colonies with umbilicated center
3 morphologies exist: opaque, semi-transparent and transparent (have selective advantage, greater adherence)

Fastidious: viability reduced if they dry at room temp – enriched culture medium is necessary for growth

Facultative anaerobes (all ferment glucose)

In aerobic conditions (ie blood agar) Þ a -hemolysis (produce RBC catalase or peroxidase)

In anaerobic conditions Þ b -hemolysis (by an oxygen labile pneumolysin, pneumolysin O)

Sensitivity: to bile salts (bile solubility) and optochin; differs from all other streps in this respect

bile solubility Þ activates amidase Þ cleaves peptidoglycan bond between alanine and muramic acid Þ lysis Polysaccharide capsules: antiphagocytic; antigenic (> 85 distinct types); confers virulence

specific antibody to the capsule opsonizes the organism, facilitates phagocytosis, and promotes resistance

specific antibody results from either infection (B cell response) or administration of polysaccharide vaccine

Antigenic structure:

Capsular antigen: hydrophillic, antiphagocytic
Somatic antigen: C polysaccharide (teichoic acid polymer), F antigen; M protein (not anti-phagocytic)

quellung reaction: capsular precipitation reaction used to rapidly identify pneumococci

With type-specific antiserum (i.e., homologous type-specific antibody) mixed with methylene blue, capsules swell (quellung reaction) producing a "halo" appearance

DNA transformation between species: of antibody resistance, type specificity and other genetic markers

Cell wall composition:

peptidoglycan and teichoic acid are major components (responsible for intense inflammation this bug produces)

lipoteichoic acid: inhibitor of homologous autolytic enzyme (N-acetylmuramyl-L-alanine) that regulates peptidoglycan hydrolase activity

choline (component of teichoic acid): regulatory ligand memb; in its absence Þ resistance to autolysins, aberrant cell division, incompetence in transformation and phage resistance

Virulence: aggressive interaction with vascular endothelial cells (type II pneumocytes if in the lung) Þ 2-3% invade, transmigration into the cells Þ endothelial cells are separated Þ loss of cell-cell contact Þ cells express G-protein coupled PAF(platelet activating factor) and procoagulant (inflammatory activation) Þ shifts targeting of the pneumococcus to the PAF receptor Þ enhances adherence Þ cytokine (IL-1, TNF) and coagulation factors (thrombin) are released which facilitate leukocyte migration

Virulence factors: capsule; pneumolysin; neuraminidase, IgA, protease, pspA, psaA, autolysin; cell wall peptidoglycan/glycopeptides

Transmission

Humans are the natural host; no animal reservoir

Obligate parasite that is spread from person to person by direct contact with respiratory secretions

Infection results from acquisition of previously unencountered capsular types (84 serotypes)

Different capsular serotypes cause infections at different times of life

Pneumococcal infections are not communicable since pneumoccoci are found in the upper respiratory tract of 5-7% of normal adults and is responsible for 70% of community-acquired bacterial pneumonia

Resistance is high in healthy young people and disease results when predisposing factors are present

Pathogenesis

Capsule Adherence

Enzymes: neuraminidase and protease

Toxins: pneumolysin O, purpura producing principle, autolysin

Pathogenesis

Produce no toxins which play a role in pathogenesis

Produce IgA protease Þ enhances ability to colonize mucosa of upper respiratory tract

Pneumococci multiply in tissues and cause inflammation

During recovery, pneumococci are phagocytized, mononuclear cells ingest debris, and consolidation resolves

Predisposing factors to infection:

alcohol or drug intoxication (or other cerebral impairments) Þ depress cough reflex and Ý aspiration of secretions

abnormality of respiratory tract (e.g., viral infections), pooling of mucus, bronchial obstruction, or respiratory tract injury

abnormal circulatory dynamics (e.g., pulmonary congestion and heart failure)

splenectomy

certain chronic diseases: sickle cell anemia and nephrosis

trauma to head that causes leakage of spinal fluid through the nose – predisposes to pneumococcal meningitis

Clinical Findings

Pneumococcal bacteremia – primary disease occurs in 25% of cases, sickle cell, multiple myeloma, CLL, functional asplenia

Pneumococcal pneumonia

manifestations:

coryza (common cold), abrupt shaking, chill, fever, pleuritic pain, cough, shortness of breath, rust colored sputum

results from rapid multiplication of bacteria in alveolar spaces Þ complete healing with no tissue necrosis

lobar pneumonia more likely in adults; bronchopneumonia more likely in children and elderly

laboratory:

PMNs in sputum, gram(+) cocci, blood culture, leukocytosis, leukopenia (ß WBC count), lobar infiltrate

hypoxemia, acidosis, DIC (disseminated intravascular coagulation)

lots of PMNs with few bugs

complications:

pleural effusion (most common: 25%) and empyema (infected pleural space), atelectasis, delayed resolution, abscess, pericarditis (rare), arthritis (rare but can occur in elderly), endocarditis, meningitis, paralytic ileus, hepatitis, death

Pneumococcal meningitis

one of most common causes of meningitis (with H.flu and meningococcus)
can result from pneumonia, otitis, mastoiditis, sinusitis, skull fracture, multiple myeloma
chills, fever, headache, stiff neck, Kernig's and Brudzinski's sign, delirium
couldy greenish spinal fluid
lots of bacteria with few PMNs

Pneumococcal endocarditis – rare, usually of aortic valve

fever, splenomgaly, arthritis
requires surgery

Pneumococcal peritonitis

young girls (seen in pediatrics)
etiology: entry from the vagina via the fallopian tubes
absence of liver or kidney disease and ascites predisposes (nephrotic syndrome, cirrhosis, carcinoma of liver)

Other diseases caused by pneumococci:

otitis media – 75-90% of children suffer an attack

mastoidits (rare) and sinusitis – can lead to meningitis and brain abscess

purulent bronchitis

sepsis

spontaneous recovery usually begins in 5-10 days, and is accompanied by the development of anticapsular antibodies.

Laboratory diagnosis

optochin sensitivity (inhibits growth)

bile solubility (bile salts activate amidase leading to lysis)

quellung reaction

mouse virulence test (animal inoculation): IP injection; all except type 14

Treatment

most pneumococci are susceptible to penicillin and erythromycin

if severe, penicilllin G is the drug of choice; if mild, penicillin V can be used

if patient is allergic to penicillin, erythromycin or derivatives (azithromycin) can be used

about 25% of isolates exhibit low-level resistance (about 7% show high level resistance) to penicillin (via altering penicillin binding proteins)

if multiresistant, can treat with vancomycin

pneumococci have also acquired resistance for: chloramphenicol, bactrim, erythromycin, tetracycline, aminoglycosides, and quinilones (resistance mediated by transposons such as tn1545)

they do not produce beta-lactamases although beta-lactams are losing efficiency against pneumococcal infections

Prevention

despite efficacy of antimicrobial drug treatment, mortality rate is high in the elderly (more than 65 years old), immunocompromised (such as splenectomized), or debilitated patients

immunize these patients with the polyvalent (23-type) polysaccharide vaccine – provides long-lasting protection (at least 5 years)

oral penicillin is given to young children with hypogammaglobulinemia or splenectomy (prone to infections and poor response to the vaccine if under 2 years old)