Streptococcus pneumoniae

Background

Gram-positive, lancet-shaped diplococcus
90+ serotypes, based on capsular polysaccharide that is bound to peptidoglycan
Lab identification is based on catalase-negative, α-hemolysis of blood agar (from pneumolysin), optochin susceptibility, and bile salt solubility
Via transformation, bacteria can exchange genetic material with each other

CLSI penicillin breakpoints for susceptibility changed in 2008
- For meningitis: ≤0.06 μg/mL
- For other infections: ≤2 μg/mL

Penicillin resistance
- S. pneumoniae has 6 PBPs: 1A, 1B, 2A, 2B, 2X, and 3
- Resistance in any of the PBPs can increase the MIC
- Mutations in PBP 2B are associated with low-level resistance
- Mutations in PBP 2X are associated with high-level resistance
Macrolide resistance
- ermB encodes an enzyme that methylates the 23S subunit, blocking macrolides and giving very high MIC ≥64
- mefA encodes an efflux pump that gives a relatively lower MIC ≤16

Present worldwide
Major cause of morbidity and mortality in children
- Leading cause of under-5 mortality worldwide

Acquired by coughing and sneezing
Asymptomatic carriage or colonization in the nasopharynx
Invasion through epithelial cells into the bloodstream, using the PAF and pIg receptors
Capsule and various proteins help it to evade immune system

4-10% in the general adult population, usually lasting several weeks
Highest in children, up to 30-60% depending on the situation, lasting up to 6 months

Acute onset of cough (92%), fatigue (63%), shortness of breath (47%), and dyspnea (23%) with documented or subjective fever (92%), chills (77%), sweats, purulent sputum, and pleuritic chest pain (79%)

Most common cause of meningitis in adults
Acquired by hematogenous spread from nasopharynx, or direct invasion from sinuses
May be secondary to otitis media or sinusitis
CSF leaks and other defects predispose to infection
Diagnostic yield in CSF decrease significantly 4 hours after administration of antibiotics

Essentially two forms of vaccine available in Canada
- 13-valent pneumococcal conjugate vaccine (Pneu-C-13), which is more immunogenic
  - Includes serotypes 4, 9V, 6B, 14, 18C, 19F, 23F, 1, 5, 7F, 3, 6A, and 19A
- 23-valent pneumococcal polysaccharide vaccine (Pneu-C-23), which includes more strains
  - Includes above serotypes except 6A, plus 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F
Pneu-C-13 is part of routine childhood immunizations, which Pneu-P-23 is used for most adults

Age	Status	Vaccine
18-64	high risk for invasive disease	PP-23 ± booster at 5 years
18-64	smoking, alcohol, homeless, LTC	PP-23
≥65	regardless of prior vaccination	PP-23 at least 5 years after last dose and 8 weeks after a dose of PC-13
≥18	immunocompromised	PC-13 followed by PP-23 with booster at 5 years
≥18	HSCT recipient	PC-13 x3 q4wk starting 3-9 months post-transplant, followed by PP-23 6-12 months later ± booster at 1 year

Conditions with high risk for invasive disease include (highest risk are bolded):
- CSF leak, chronic neurologic conditions that impair clearance of oral secretions, cochlear implants, chronic heart disease, diabetes mellitus, chronic kidney disease, chronic liver disease including cirrhosis, and chronic lung disease including asthma requiring medical care within past 12 months
- Immunocompromising conditions, including hyposplenia (including sickle cell disease, asplenia, or splenic dysfunction), primary immunodeficiency, therapeutic immune suppression (including corticosteroids, chemotherapy, radiation therapy, and transplantation), HIV, HSCT, malignancy, nephrotic syndrome, solid organ transplantation