Streptococcus pneumoniae: Difference between revisions

Latest revision as of 15:15, 17 September 2023

Background

Microbiology

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

Antibiotic Resistance

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

Epidemiology

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

Pathophysiology

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

Clinical Manifestations

Asymptomatic Carriage

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

Otitis Media

Sinusitis

Bacteremia

Pneumonia

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%)

Meningitis

Most common cause of bacterial 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

Management

Scenario	Penicillin (μg/mL)			Ceftriaxone (μg/mL)
Scenario	S	I	R	S	I	R
Non-meningitic oral	≤0.06	0.12-1	≥2
Non-meningitic parenteral	≤2	4	≥8	≤1	2	≥4
Meningitic parenteral	≤0.06		≥0.12	≤0.5	1	≥2

Prevention

Vaccination

Essentially two forms of vaccine available in Canada
- Pneu-C-13: 13-valent pneumococcal conjugate vaccine (Prevnar-13)
  - More immunogenic, but fewer serotypes
  - Routine childhood immunization, also used for immunocompromised adults
  - Includes serotypes: 4, 9V, 6B, 14, 18C, 19F, 23F, 1, 5, 7F, 3, 6A, and 19A
  - Given at least 1 year after Pneu-P-23
- Pneu-P-23: 23-valent pneumococcal polysaccharide vaccine (Pneumovax)
  - Less immunogenic, but more serotypes
  - Routine immunization in elderly
  - Includes above serotypes (except 6A), plus 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F
  - Given at least 8 weeks after Pneu-C-13 and at least 5 years after most recent Pneu-P-23 (except HSCT patients)
  - Booster given at 5 years if they are at risk of poor antibody response

Age	Status	Vaccine
<18	routine	2 to 4 doses PC-13, depending on age
18-64	healthy	no routine vaccination
	smoking, alcohol, injection drug use, homeless, long-term care facility	1 dose PP-23
	high risk for invasive disease	1 dose PP-23 ± booster at 5 years
≥18	immunocompromised	1 dose PC-13, followed in 8 weeks by 1 dose PP-23 with booster at 5 years
≥18	HSCT recipient	3 doses PC-13 q4wk starting 3-9 months post-transplant, followed 6-12 months later by 1 dose PP-23 ± booster at 1 year
≥65	healthy, regardless of prior vaccination	1 dose PP-23

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: 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

Post-Exposure Management

Per Public Health Ontario, no specific management is required for close contacts

@@ Line 1: / Line 1: @@
-== Microbiology ==
+==Background==
+===Microbiology===
-* [[Has Gram stain::Gram-positive]], lancet-shaped diplococci
+*[[Stain::Gram-positive]], lancet-shaped [[Shape::coccus|diplococcus]]
-* 90+ serotypes, based on capsular polysaccharide that is bound to peptidoglycan
+*90+ serotypes, based on capsular polysaccharide that is bound to peptidoglycan
-* Lab identification is based on [[Has hemolysis pattern::α-hemolysis]] of blood agar (from pneumolysin), [[Has susceptibility to::optochin]] susceptibility, and bile salt solubility
+*Lab identification is based on catalase [[Catalase::negative]], [[Hemolysis pattern::α]] hemolysis of blood agar (from pneumolysin), [[Susceptible to::optochin]] susceptibility, and bile salt solubility
+*Via transformation, bacteria can exchange genetic material with each other
+===Antibiotic Resistance===
-== Epidemiology ==
+*'''[[Penicillin]]''' resistance
-* Present worldwide
+**''S. pneumoniae'' has 6 PBPs: 1A, 1B, 2A, 2B, 2X, and 3
-* Major cause of morbidity and mortality in children
+**Resistance in any of the PBPs can increase the MIC
-** Leading cause of under-5 mortality worldwide
+**Mutations in PBP 2B are associated with low-level resistance
+**Mutations in PBP 2X are associated with high-level resistance
+*'''[[Macrolides|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
+===Epidemiology===
+*Present worldwide
+*Major cause of morbidity and mortality in children
+**Leading cause of under-5 mortality worldwide
+===Pathophysiology===
+*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
+==Clinical Manifestations==
+===Asymptomatic Carriage===
+*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
+===Otitis Media===
+===Sinusitis===
+===Bacteremia===
+===Pneumonia===
+*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%)
+===Meningitis===
+*Most common cause of [[bacterial 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
+==Management==
+{| class="wikitable"
+! rowspan="2" |Scenario
+! colspan="3" |Penicillin (μg/mL)
+! colspan="3" |Ceftriaxone (μg/mL)
+|-
+!S
+!I
+!R
+!S
+!I
+!R
+|-
+|Non-meningitic oral
+|≤0.06
+|0.12-1
+|≥2
+|
+|
+|
+|-
+|Non-meningitic parenteral
+|≤2
+|4
+|≥8
+|≤1
+|2
+|≥4
+|-
+|Meningitic parenteral
+|≤0.06
+|
+|≥0.12
+|≤0.5
+|1
+|≥2
+|}
+==Prevention==
+===Vaccination===
+*Essentially two forms of vaccine available in Canada
+**Pneu-C-13: 13-valent pneumococcal conjugate vaccine (Prevnar-13)
+***More immunogenic, but fewer serotypes
+***Routine childhood immunization, also used for immunocompromised adults
+***Includes serotypes: 4, 9V, 6B, 14, 18C, 19F, 23F, 1, 5, 7F, 3, 6A, and 19A
+***Given at least 1 year after Pneu-P-23
+**Pneu-P-23: 23-valent pneumococcal polysaccharide vaccine (Pneumovax)
+***Less immunogenic, but more serotypes
+***Routine immunization in elderly
+***Includes above serotypes (except 6A), plus 2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, and 33F
+***Given at least 8 weeks after Pneu-C-13 and at least 5 years after most recent Pneu-P-23 (except HSCT patients)
+***Booster given at 5 years if they are at risk of poor antibody response
+{| class="wikitable"
+!Age
+!Status
+!Vaccine
+|-
+|<18
+|routine
+|2 to 4 doses PC-13, depending on age
+|-
+| rowspan="3" |18-64
+|healthy
+|no routine vaccination
+|-
+|[[Tobacco use disorder|smoking]], [[Alcohol use disorder|alcohol]], injection drug use, homeless, long-term care facility
+|1 dose PP-23
+|-
+|high risk for invasive disease
+|1 dose PP-23 ± booster at 5 years
+|-
+| rowspan="2" |≥18
+|immunocompromised
+|1 dose PC-13, followed in 8 weeks by 1 dose PP-23 with booster at 5 years
+|-
+|HSCT recipient
+|3 doses PC-13 q4wk starting 3-9 months post-transplant, followed 6-12 months later by 1 dose PP-23 ± booster at 1 year
+|-
+|≥65
+|healthy, regardless of prior vaccination
+|1 dose PP-23
+|}
+*'''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''': [[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]]
+=== Post-Exposure Management ===
+* Per Public Health Ontario, no specific management is required for close contacts
 {{DISPLAYTITLE:''Streptococcus pneumoniae''}}
 [[Category:Gram-positive cocci]]