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’
== Background ==
 +
==Background==
βˆ’
=== Microbiology ===
 +
===Microbiology===
βˆ’
* [[Has Gram stain::Gram-positive]] coccus, typically in short chains
  
βˆ’
* Non-motile, non–spore forming, catalase-negative, and facultatively anaerobic
  
βˆ’
* [[Has hemolysis pattern::Ξ² hemolytic]] on blood agar (complete hemolysis)
  
βˆ’
* Can be distinguished from other Ξ²-hemolytic streptococci by its susceptibility to [[bacitracin]]
  
   
  +
*[[Stain::Gram-positive]] [[Shape::coccus]], typically in short chains
βˆ’
=== Pathophysiology ===
  
  +
*Non-motile, non–spore forming, catalase [[Catalase::negative]], and facultatively anaerobic
βˆ’
==== Virulence factors ====
  
  +
*[[Hemolysis pattern::Ξ² hemolytic]] on blood agar (complete hemolysis)
βˆ’
* Capsular '''hyaluronic acid''' is similar to human
  
  +
*Can be distinguished from other Ξ²-hemolytic streptococci by its susceptibility to [[bacitracin]]
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
  
   
  +
===Pathophysiology===
βˆ’
==== Antibiotic resistance ====
  
  +
====Virulence Factors====
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
  
   
  +
*Capsular '''hyaluronic acid''' is similar to human
βˆ’
== Clinical Presentation ==
  
  +
*'''M protein''' is the main factor imparting virulence
βˆ’
* Asymptomatic carriage
  
  +
**M protein differences given ''S. pyogenes'' its serotypes (about 150)
βˆ’
* Streptococcal [[pharyngitis]]
  
  +
**Confers resistance to phagocytosis by modulating host immune response
βˆ’
* [[Scarlet fever]]
  
  +
**Impairs granulocyte maturation even if it is phagocytosed
βˆ’
* Skin and soft tissue infections, including [[cellulitis]], [[erysipelas]], [[impetigo]], and [[necrotizing fasciitis]]
  
  +
**It is also an adhesin
βˆ’
* Upper and lower respiratory tract infections
  
  +
*'''F protein''' binds to fibronectin, helps with adhesion
βˆ’
* [[Bacteremia]] without a focus
  
  +
*Hemolysins, include '''streptolysin O and S''', confers red and white cell lysis
βˆ’
* [[Septic arthritis]] and [[osteomyelitis]]
  
  +
**O means oxygen-labile, so will only grow in anaerobic environment, while S is stable in oxygen
βˆ’
* [[Myositis]]
  
  +
*'''DNAse''' (streptokinase) disrupts coagulation and the body's ability to prevent the bacteria from spreading
βˆ’
* Pelvic infections, including [[postpartum endometritis]] (puerperal fever)
  
βˆ’
* [[Streptococcal 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
  
βˆ’
** Sudden unexplained death in an otherwise healthy person
  
βˆ’
* Post-infectious syndromes
  
βˆ’
** [[Acute rheumatic fever]]
  
βˆ’
** [[Post-infectious glomerulonephritis]]
  
βˆ’
** [[PANDAS]]
  
   
  +
====Antibiotic Resistance====
βˆ’
== 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]
  
   
  +
*Ξ²-lactam resistance: the PBP is extremely stable, so low mutation rate, and essentially always susceptible to [[penicillin]]
βˆ’
=== Confirmed case ===
  
  +
*Macrolide resistance, via two mechanisms[[CiteRef::michos2009ma]]
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
  
  +
**''mefA'' gene encoding a macrolide efflux pump, conferring an M phenotype (macrolide resistance alone)
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).
  
  +
**''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’
=== 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
  
   
  +
*Asymptomatic carriage
βˆ’
=== Clinical evidence ===
  
  +
*Streptococcal [[pharyngitis]]
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:
  
  +
*[[Scarlet fever]]
βˆ’
* Renal impairment (creatinine level β‰₯ 177 ΞΌmol/L for adults)
  
  +
*Skin and soft tissue infections, including [[cellulitis]], [[erysipelas]], [[impetigo]], and [[necrotizing fasciitis]]
βˆ’
* Coagulopathy (platelet count ≀ 100,000/mm3 or disseminated intravascular coagulation)
  
  +
*Upper and lower respiratory tract infections
βˆ’
* Liver function abnormality (SGOT, SGPT, or total bilirubin β‰₯ 2x upper limit of normal)
  
  +
*[[Bacteremia]] without a focus
βˆ’
* Adult respiratory distress syndrome
  
  +
*[[Septic arthritis]] and [[osteomyelitis]]
βˆ’
* Generalized erythematous macular rash that may desquamate
  
  +
*[[Myositis]]
βˆ’
* Soft-tissue necrosis, including necrotizing fasciitis, myositis or gangrene
  
  +
*Pelvic infections, including [[postpartum endometritis]] (puerperal fever)
βˆ’
* Meningitis
  
  +
*[[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’
== Management ==
  
βˆ’
* Generally treated with [[Is treated by::penicillin]] or cephalosporins
  
   
  +
*[[Acute rheumatic fever]]
βˆ’
== Prevention ==
  
  +
*[[Post-infectious glomerulonephritis]]
βˆ’
=== Prophylaxis ===
  
  +
*[[PANDAS]]
βˆ’
* Prophylaxis is indicated for '''close contacts''' of a case of '''severe''' invasive group A streptococcal infection; specically:
  
βˆ’
** Exposure between 7 days before symptom onset to 24 hours after starting antimicrobial treatment
  
βˆ’
** Severe infections include toxic shock syndrome, necrotizing skin and soft tissue infections, meningitis, pneumonia, other life-threatening conditions, or a confirmed case resulting in death
  
βˆ’
** Close contacts include:
  
βˆ’
*** Household contacts who have spent at least 4 hours/day on average in the previous 7 days or 20 hours/week
  
βˆ’
*** Non-household persons who share the same bed with the case or had sexual relations with the case
  
βˆ’
*** 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
  
βˆ’
*** Injection drug users who have shared needles with the case
  
βˆ’
*** Selected LTCF contacts
  
βˆ’
*** Selected child care contacts (see Section 6.4)
  
βˆ’
*** Selected hospital contacts (see Annex 3)
  
βˆ’
* First-line: [[Is treated by::cephalexin]] 25 to 50 mg/kg (max 1 g) daily split bid to qid for 10 days
  
βˆ’
* Second-line depends on local antimicrobial resistance patterns:
  
βˆ’
** [[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
  
βˆ’
** [[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
  
βˆ’
** [[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
  
   
  +
==Classification of Invasive Disease==
βˆ’
== Prognosis ==
  
  +
βˆ’
* Highest risk of streptococcal [[toxic shock syndrome]] (TSS) or death
  
  +
*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’
** [[Necrotizing fasciitis]] (50% and 50%)
  
  +
βˆ’
** Pneumonia (30% and 30%)
  
  +
===Confirmed Case===
βˆ’
** Bacteremia (15% and 25%)
  
  +
  +
*'''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 ===
  +
  +
* [[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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