Streptococcus pyogenes

• 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
• β hemolytic on blood agar (complete hemolysis)
• Can be distinguished from other β-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

• β-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 MLS_B phenotype (macrolide-lincosamide-streptogramin B resistance), which is detectable using a D test
  • Rarely, ermB gene similar to ermA

Clinical Manifestations

• Asymptomatic carriage
• 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

• Acute rheumatic fever
• Post-infectious glomerulonephritis
• PANDAS

Classification of Invasive Disease

• As per the Public Health Agency of Canada National case definition: Invasive group A streptococcal 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 ≥ 177 μmol/L for adults)
  • Coagulopathy (platelet count ≤ 100,000/mm3 or disseminated intravascular coagulation)
  • Liver function abnormality (SGOT, SGPT, or total bilirubin ≥ 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 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 clarithromycin2
  • Often susceptible to tetracycline and doxycycline (10-15% resistance)3
  • Probably susceptible to cotrimoxazole, with early reports of resistance due to spurious in vitro effects43

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

• Highest risk of streptococcal toxic shock syndrome (TSS) or death
  • Necrotizing fasciitis (50% and 50%)
  • Pneumonia (30% and 30%)
  • Bacteremia (15% and 25%)