Streptococcus pyogenes: Difference between revisions

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Streptococcus pyogenes
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βˆ’
* Also commonly referred to as Group A Streptococcus
 +
*Also commonly referred to as '''Group A Streptococcus'''
   
βˆ’
== Microbiology ==
 +
==Background==
  +
===Microbiology===
   
βˆ’
* [[Has Gram stain::Gram-positive]] coccus, typically in short chains
 +
*[[Stain::Gram-positive]] [[Shape::coccus]], typically in short chains
βˆ’
* Non-motile, non–spore forming, catalase-negative, and facultatively anaerobic
 +
*Non-motile, non–spore forming, catalase [[Catalase::negative]], and facultatively anaerobic
βˆ’
* [[Has hemolysis pattern::Ξ² hemolytic]] on blood agar (complete hemolysis)
 +
*[[Hemolysis pattern::Ξ² hemolytic]] on blood agar (complete hemolysis)
  +
*Can be distinguished from other Ξ²-hemolytic streptococci by its susceptibility to [[bacitracin]]
   
βˆ’
== Pathophysiology ==
 +
===Pathophysiology===
  +
====Virulence Factors====
   
  +
*Capsular '''hyaluronic acid''' is similar to human
βˆ’
=== Virulence factors ===
  
  +
*'''M protein''' is the main factor imparting virulence
  +
**M protein differences given ''S. pyogenes'' its serotypes (about 150)
  +
**Confers resistance to phagocytosis by modulating host immune response
  +
**Impairs granulocyte maturation even if it is phagocytosed
  +
**It is also an adhesin
  +
*'''F protein''' binds to fibronectin, helps with adhesion
  +
*Hemolysins, include '''streptolysin O and S''', confers red and white cell lysis
  +
**O means oxygen-labile, so will only grow in anaerobic environment, while S is stable in oxygen
  +
*'''DNAse''' (streptokinase) disrupts coagulation and the body's ability to prevent the bacteria from spreading
   
  +
====Antibiotic Resistance====
βˆ’
* Capsular '''hyaluronic acid''' is similar to human
  
βˆ’
* '''M protein''' is the main factor imparting virulence
  
βˆ’
** M protein differences given ''S. pyogenes'' its serotypes (about 150)
  
βˆ’
** Confers resistance to phagocytosis by modulating host immune response
  
βˆ’
** Impairs granulocyte maturation even if it is phagocytosed
  
βˆ’
** It is also an adhesin
  
βˆ’
* '''F protein''' binds to fibronectin, helps with adhesion
  
βˆ’
* Hemolysins, include '''streptolysin O and S''', confers red and white cell lysis
  
βˆ’
** O means oxygen-labile, so will only grow in anaerobic environment, while S is stable in oxygen
  
βˆ’
* '''DNAse''' (streptokinase) disrupts coagulation and the body's ability to prevent the bacteria from spreading
  
   
  +
*Ξ²-lactam resistance: the PBP is extremely stable, so low mutation rate, and essentially always susceptible to [[penicillin]]
βˆ’
=== Antibiotic resistance ===
  
  +
*Macrolide resistance, via two mechanisms[[CiteRef::michos2009ma]]
  +
**''mefA'' gene encoding a macrolide efflux pump, conferring an M phenotype (macrolide resistance alone)
  +
**''ermA'' gene encoding inducible methylation of 23S ribosome, conferring an MLS<sub>B</sub> phenotype (macrolide-lincosamide-streptogramin B resistance), which is detectable using a [[D test]]
  +
**Rarely, ''ermB'' gene similar to ''ermA''
   
  +
==Clinical Manifestations==
βˆ’
* The PBP is extremely stable, so low mutation rate, and essentially always susceptible to penicillin
  
βˆ’
* Macrolides
  
βˆ’
** Inducible in the presence of erythromycin (D test)
  
βˆ’
** Efflux pump
  
   
  +
*Asymptomatic carriage
βˆ’
== Clinical Presentation ==
  
  +
*Streptococcal [[pharyngitis]]
  +
*[[Scarlet fever]]
  +
*Skin and soft tissue infections, including [[cellulitis]], [[erysipelas]], [[impetigo]], and [[necrotizing fasciitis]]
  +
*Upper and lower respiratory tract infections
  +
*[[Bacteremia]] without a focus
  +
*[[Septic arthritis]] and [[osteomyelitis]]
  +
*[[Myositis]]
  +
*Pelvic infections, including [[postpartum endometritis]] (puerperal fever)
  +
*[[Streptococcal toxic shock syndrome]]
  +
*Less commonly:
  +
**[[Pneumonia]], typically post-viral and associated with military recruits, and often complicated by empyema and 38% mortality
  +
**[[Lymphangitis]]
  +
**[[Meningitis]]
  +
**[[Endocarditis]]
  +
**[[Sudden unexplained death]] in an otherwise healthy person
   
  +
===Post-Infectious Syndromes===
βˆ’
* Streptococcal [[pharyngitis]]
  
βˆ’
* [[Scarlet fever]]
  
βˆ’
* Skin and soft tissue infections, including [[cellulitis]], [[erysipelas]], [[impetigo]], and [[necrotizing fasciitis]]
  
βˆ’
* Upper and lower respiratory tract infections
  
βˆ’
* [[Bacteremia]] without a focus
  
βˆ’
* [[Septic arthritis]] and [[osteomyelitis]]
  
βˆ’
* [[Myositis]]
  
βˆ’
* Pelvic infections, including [[postpartum endometritis]] (puerperal fever)
  
βˆ’
* [[Toxic_shock_syndromes#Streptococcal_Toxic_Shock_Syndrome|Toxic shock syndrome]]
  
βˆ’
* Less commonly:
  
βˆ’
** Pneumonia, typically post-viral and associated with military recruits, and often complicated by empyema and 38% mortality
  
βˆ’
** Lymphangitis
  
βˆ’
** Meningitis
  
βˆ’
** Endocarditis
  
   
  +
*[[Acute rheumatic fever]]
βˆ’
== Classification of Invasive Disease ==
  
  +
*[[Post-infectious glomerulonephritis]]
  +
*[[PANDAS]]
   
  +
==Classification of Invasive Disease==
βˆ’
* As per the Public Health Agency of Canada [https://www.canada.ca/en/public-health/services/diseases/group-a-streptococcal-diseases/health-professionals/national-case-definition.html National case definition: Invasive group A streptococcal disease]
  
   
  +
*As per the Public Health Agency of Canada [https://www.canada.ca/en/public-health/services/diseases/group-a-streptococcal-diseases/health-professionals/national-case-definition.html National case definition: Invasive group A streptococcal disease]
βˆ’
=== Confirmed case ===
  
   
  +
===Confirmed Case===
βˆ’
* '''Laboratory confirmation''' of infection with or without clinical evidence of invasive disease, requiring isolation of group A streptococcus (''Streptococcus pyogenes'') from a normally sterile site
  
βˆ’
** Blood, CSF, pleural fluid, pericardial fluid, peritoneal fluid, deep tissue specimen taken during surgery (e.g. muscle collected during debridement for necrotizing fasciitis), bone or joint fluid excluding the middle ear and superficial wound aspirates (e.g. skin and soft tissue abscesses).
  
   
  +
*'''Laboratory confirmation''' of infection with or without clinical evidence of invasive disease, requiring isolation of group A streptococcus (''Streptococcus pyogenes'') from a normally sterile site
βˆ’
=== Probable case ===
  
  +
**Blood, CSF, pleural fluid, pericardial fluid, peritoneal fluid, deep tissue specimen taken during surgery (e.g. muscle collected during debridement for necrotizing fasciitis), bone or joint fluid excluding the middle ear and superficial wound aspirates (e.g. skin and soft tissue abscesses).
   
  +
===Probable Case===
βˆ’
* '''Clinical evidence''' of invasive disease in the absence of another identified aetiology and with non-confirmatory laboratory evidence of infection:
  
βˆ’
** Isolation of group A streptococcus from a non-sterile site
  
βˆ’
** or
  
βˆ’
** Positive group A streptococcus antigen detection
  
   
  +
*'''Clinical evidence''' of invasive disease in the absence of another identified aetiology and with non-confirmatory laboratory evidence of infection:
βˆ’
=== Clinical evidence ===
  
  +
**Isolation of group A streptococcus from a non-sterile site, or
  +
**Positive group A streptococcus antigen detection
   
  +
===Clinical Evidence===
βˆ’
* Streptococcal toxic shock syndrome, which is characterized by hypotension (systolic blood pressure ≀ 90 mm Hg in an adult and < 5 percentile for age for children) and at least two of the following signs:
  
βˆ’
* Renal impairment (creatinine level β‰₯ 177 ΞΌmol/L for adults)
  
βˆ’
* Coagulopathy (platelet count ≀ 100,000/mm3 or disseminated intravascular coagulation)
  
βˆ’
* Liver function abnormality (SGOT, SGPT, or total bilirubin β‰₯ 2x upper limit of normal)
  
βˆ’
* Adult respiratory distress syndrome
  
βˆ’
* Generalized erythematous macular rash that may desquamate
  
βˆ’
* Soft-tissue necrosis, including necrotizing fasciitis, myositis or gangrene
  
βˆ’
* Meningitis
  
   
  +
*[[Streptococcal toxic shock syndrome]], which is characterized by hypotension (systolic blood pressure ≀ 90 mm Hg in an adult and < 5 percentile for age for children) and at least two of the following signs:
βˆ’
== Prognosis ==
  
  +
**Renal impairment (creatinine level β‰₯ 177 ΞΌmol/L for adults)
  +
**Coagulopathy (platelet count ≀ 100,000/mm3 or disseminated intravascular coagulation)
  +
**Liver function abnormality (SGOT, SGPT, or total bilirubin β‰₯ 2x upper limit of normal)
  +
**Adult respiratory distress syndrome
  +
**Generalized erythematous macular rash that may desquamate
  +
**Soft-tissue necrosis, including necrotizing fasciitis, myositis or gangrene
  +
**Meningitis
   
  +
== Diagnosis ==
βˆ’
* Highest risk of streptococcal [[toxic shock syndrome]] (TSS) or death
  
  +
βˆ’
** [[Necrotizing fasciitis]] (50% and 50%)
  
  +
* Typically by traditional bacteriology/culture
βˆ’
** Pneumonia (30% and 30%)
  
  +
βˆ’
** Bacteremia (15% and 25%)
  
  +
=== Serology ===
  +
  +
* [[Antistreptolysin O]] is occasionally useful for diagnosis of [[acute rheumatic fever]], and far less useful for [[streptococcal pharyngitis]] and [[post-streptococcal glomerulonephritis]]
  +
  +
=== Rapid Antigen Detection Test ===
  +
  +
* Used for diagnosing group A streptococcal pharyngitis
  +
* Specificity 95% and sensitivity 70-90%
  +
* False positives with GAS colonization/carriage
  +
  +
==Management==
  +
  +
*Generally treated with [[Is treated by::penicillin]] or [[cephalosporins]]
  +
*Susceptible to beta-lactams, [[clindamycin]], [[chloramphenicol]], [[rifampin]], [[teicoplanin]], and [[vancomycin]], but resistant to [[fusidic acid]], and [[fosfomycin]]; usually susceptible to [[ciprofloxacin]], [[erythromycin]], and [[clarithromycin]][[CiteRef::traub1997co]]
  +
**Often susceptible to [[tetracycline]] and [[doxycycline]] (10-15% resistance)[[CiteRef::melo-cristino2015an]]
  +
**Probably susceptible to [[cotrimoxazole]], with early reports of resistance due to spurious in vitro effects[[CiteRef::bowen2012is]][[CiteRef::melo-cristino2015an]]
  +
  +
==Prevention==
  +
===Prophylaxis===
  +
  +
*The risk of invasive streptococcal infection for close contacts is 20-200 times higher than the population average, which is still low
  +
*Prophylaxis is indicated for '''close contacts''' of a case of '''severe''' invasive group A streptococcal infection; specifically:
  +
**Exposure between 7 days before symptom onset to 24 hours after starting antimicrobial treatment
  +
**Severe infections include [[Streptococcal toxic shock syndrome|toxic shock syndrome]], [[necrotizing skin and soft tissue infection]], [[Bacterial meningitis|meningitis]], [[pneumonia]], other life-threatening conditions, or a confirmed case resulting in death
  +
**Close contacts include:
  +
***Household contacts who have spent at least 4 hours/day on average in the previous 7 days or 20 hours/week
  +
***Non-household persons who share the same bed with the case or had sexual relations with the case
  +
***Persons who have had direct mucous membrane contact with the oral or nasal secretions of a case (e.g. mouth-to-mouth resuscitation, open mouth kissing) or unprotected direct contact with an open skin lesion of the case
  +
***Injection drug users who have shared needles with the case
  +
***Selected LTCF contacts
  +
***Selected child care contacts
  +
***Selected hospital contacts
  +
*First-line: [[Is treated by::cephalexin]] 25 to 50 mg/kg (max 1 g) daily split bid to qid for 10 days
  +
*Second-line depends on local antimicrobial resistance patterns:
  +
**[[Is treated by::Erythromycin]] 5 to 7.5 mg/kg po q6h (or 10 to 15 mg/kg po q12h) in children, or 500 mg po q12h in adults, for 10 days
  +
**[[Is treated by::Clarithromycin]] 7.5 mg/kg (max 250 mg) po q12h in children, or 250 mg po bid in adults, for 10 days
  +
**[[Is treated by::Clindamycin]] 8 to 16 mg/kg po daily split tid or qid in children, or 150 mg po qid in adults, for 10 days
  +
  +
==Prognosis==
  +
  +
*Highest risk of streptococcal [[toxic shock syndrome]] (TSS) or death
  +
**[[Necrotizing fasciitis]] (50% and 50%)
  +
**[[Pneumonia]] (30% and 30%)
  +
**[[Streptococcus bacteremia|Bacteremia]] (15% and 25%)
   
 
{{DISPLAYTITLE:''Streptococcus pyogenes''}}
  
{{DISPLAYTITLE:''Streptococcus pyogenes''}}

Latest revision as of 18:26, 8 June 2023

  • Also commonly referred to as Group A Streptococcus

Background

Microbiology

  • Gram-positive coccus, typically in short chains
  • Non-motile, non–spore forming, catalase negative, and facultatively anaerobic
  • Ξ² hemolytic on blood agar (complete hemolysis)
  • Can be distinguished from other Ξ²-hemolytic streptococci by its susceptibility to bacitracin

Pathophysiology

Virulence Factors

  • Capsular hyaluronic acid is similar to human
  • M protein is the main factor imparting virulence
    • M protein differences given S. pyogenes its serotypes (about 150)
    • Confers resistance to phagocytosis by modulating host immune response
    • Impairs granulocyte maturation even if it is phagocytosed
    • It is also an adhesin
  • F protein binds to fibronectin, helps with adhesion
  • Hemolysins, include streptolysin O and S, confers red and white cell lysis
    • O means oxygen-labile, so will only grow in anaerobic environment, while S is stable in oxygen
  • DNAse (streptokinase) disrupts coagulation and the body's ability to prevent the bacteria from spreading

Antibiotic Resistance

  • Ξ²-lactam resistance: the PBP is extremely stable, so low mutation rate, and essentially always susceptible to penicillin
  • Macrolide resistance, via two mechanisms1
    • mefA gene encoding a macrolide efflux pump, conferring an M phenotype (macrolide resistance alone)
    • ermA gene encoding inducible methylation of 23S ribosome, conferring an MLSB phenotype (macrolide-lincosamide-streptogramin B resistance), which is detectable using a D test
    • Rarely, ermB gene similar to ermA

Clinical Manifestations

Post-Infectious Syndromes

Classification of Invasive Disease

Confirmed Case

  • Laboratory confirmation of infection with or without clinical evidence of invasive disease, requiring isolation of group A streptococcus (Streptococcus pyogenes) from a normally sterile site
    • Blood, CSF, pleural fluid, pericardial fluid, peritoneal fluid, deep tissue specimen taken during surgery (e.g. muscle collected during debridement for necrotizing fasciitis), bone or joint fluid excluding the middle ear and superficial wound aspirates (e.g. skin and soft tissue abscesses).

Probable Case

  • Clinical evidence of invasive disease in the absence of another identified aetiology and with non-confirmatory laboratory evidence of infection:
    • Isolation of group A streptococcus from a non-sterile site, or
    • Positive group A streptococcus antigen detection

Clinical Evidence

  • Streptococcal toxic shock syndrome, which is characterized by hypotension (systolic blood pressure ≀ 90 mm Hg in an adult and < 5 percentile for age for children) and at least two of the following signs:
    • Renal impairment (creatinine level β‰₯ 177 ΞΌmol/L for adults)
    • Coagulopathy (platelet count ≀ 100,000/mm3 or disseminated intravascular coagulation)
    • Liver function abnormality (SGOT, SGPT, or total bilirubin β‰₯ 2x upper limit of normal)
    • Adult respiratory distress syndrome
    • Generalized erythematous macular rash that may desquamate
    • Soft-tissue necrosis, including necrotizing fasciitis, myositis or gangrene
    • Meningitis

Diagnosis

  • Typically by traditional bacteriology/culture

Serology

Rapid Antigen Detection Test

  • Used for diagnosing group A streptococcal pharyngitis
  • Specificity 95% and sensitivity 70-90%
  • False positives with GAS colonization/carriage

Management

Prevention

Prophylaxis

  • The risk of invasive streptococcal infection for close contacts is 20-200 times higher than the population average, which is still low
  • Prophylaxis is indicated for close contacts of a case of severe invasive group A streptococcal infection; specifically:
    • Exposure between 7 days before symptom onset to 24 hours after starting antimicrobial treatment
    • Severe infections include toxic shock syndrome, necrotizing skin and soft tissue infection, meningitis, pneumonia, other life-threatening conditions, or a confirmed case resulting in death
    • Close contacts include:
      • Household contacts who have spent at least 4 hours/day on average in the previous 7 days or 20 hours/week
      • Non-household persons who share the same bed with the case or had sexual relations with the case
      • Persons who have had direct mucous membrane contact with the oral or nasal secretions of a case (e.g. mouth-to-mouth resuscitation, open mouth kissing) or unprotected direct contact with an open skin lesion of the case
      • Injection drug users who have shared needles with the case
      • Selected LTCF contacts
      • Selected child care contacts
      • Selected hospital contacts
  • First-line: cephalexin 25 to 50 mg/kg (max 1 g) daily split bid to qid for 10 days
  • Second-line depends on local antimicrobial resistance patterns:
    • Erythromycin 5 to 7.5 mg/kg po q6h (or 10 to 15 mg/kg po q12h) in children, or 500 mg po q12h in adults, for 10 days
    • Clarithromycin 7.5 mg/kg (max 250 mg) po q12h in children, or 250 mg po bid in adults, for 10 days
    • Clindamycin 8 to 16 mg/kg po daily split tid or qid in children, or 150 mg po qid in adults, for 10 days

Prognosis

References

  1. ^  Athanasios G. Michos, Chrysanthi G. Bakoula, Maria Braoudaki, Foteini I. Koutouzi, Eleftheria S. Roma, Anastasia Pangalis, Georgia Nikolopoulou, Elena Kirikou, Vassiliki P. Syriopoulou. Macrolide resistance in Streptococcus pyogenes: prevalence, resistance determinants, and emm types. Diagnostic Microbiology and Infectious Disease. 2009;64(3):295-299. doi:10.1016/j.diagmicrobio.2009.03.004.

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