Streptococcus pyogenes

# Overview
Streptococcus pyogenes is a Bacilli Lactobacillales that grows in long chains depending on the culture method. S. pyogenes displays group A antigen on its cell wall and beta-hemolysis when cultured on blood agar plate. S. pyogenes  typically produces large zones of beta-hemolysis, the complete disruption of erythrocytes and the release of hemoglobin, and it is therefore called Group A (beta-hemolytic) Streptococcus (abbreviated GAS). Streptococci are catalase -negative.

# Serotyping
In 1928, Rebecca Lancefield published a method for serotyping S. pyogenes based on its M protein, a virulence factor that is displayed on its surface. Later in 1946, Lancefield described the serologic classification of S. pyogenes isolates based on their surface T antigen.  Four of the 20 T antigens have been revealed to be pili, which are used by bacteria to attach to host cells. Currently, over 100 M serotypes and approximately 20 T serotypes are known.

# Pathogenesis
S. pyogenes is the cause of many important human diseases ranging from mild superficial skin infections to life-threatening systemic diseases.  Infections typically begin in the throat or skin.  Examples of mild S. pyogenes infections include pharyngitis ("strep throat") and localized skin infection ("impetigo").  Erysipelas and cellulitis are characterized by multiplication and lateral spread of S. pyogenes in deep layers of the skin.  S. pyogenes invasion and multiplication in the fascia can lead to necrotizing fasciitis, a potentially life-threatening condition requiring surgical treatment.
Infections due to certain strains of S. pyogenes can be associated with the release of bacterial toxins. Throat infections associated with release of certain toxins lead to scarlet fever.  Other toxigenic S. pyogenes infections may lead to streptococcal toxic shock syndrome, which can be life-threatening.
S. pyogenes can also cause disease in the form of post-infectious "non-pyogenic" (not associated with local bacterial multiplication and pus formation) syndromes. These autoimmune mediated complications follow a small percentage of infections and include rheumatic fever and acute poststreptococcal glomerulonephritis. Both conditions appear several weeks following the initial streptococcal infection.  Rheumatic fever is characterised by inflammation of the joints and/or heart following an episode of Streptococcal pharyngitis.  Acute glomerulonephritis, inflammation of the renal glomerulus, can follow Streptococcal pharyngitis or skin infection.
This bacterium remains acutely sensitive to penicillin. Failure of treatment with penicillin is generally attributed to other local commensal organisms producing -lactamase or failure to achieve adequate tissue levels in the pharynx.  Certain strains have developed resistance to macrolides, tetracyclines and clindamycin.

# Virulence factors
S. pyogenes has several virulence factors that enable it to attach to host tissues, evade the immune response, and spread by penetrating host tissue layers.  A carbohydrate capsule composed of hyaluronic acid surrounds the bacterium, protecting it from phagocytosis by neutrophils. In addition, the capsule and several factors embedded in the cell wall, including M protein, lipoteichoic acid, and protein F (SfbI) facilitate attachment to various host cells.  M protein also inhibits opsonization by the alternative complement pathway by binding to host complement regulators.  M protein found on some serotypes are also able to prevent opsonization by binding to fibrinogen.  However, the M protein is also the weakest point in this pathogen's defense as antibodies produced by the immune system against M protein target the bacteria for engulfment by phagocytes.  M proteins are unique to each strain, and identification can be used clinically to confirm the strain causing an infection.
S. pyogenes releases a number of proteins, including several virulence factors, into its host:

# Diagnosis
Usually, a throat swab is taken to the laboratory for testing. First off, Gram stain is performed to show Gram positive, cocci, in chains. Then, culture the organism on blood agar  with added bacitracin antibiotic disk to show beta-haemolytic colonies and sensitivity (zone of inhibition around the disk) for the antibiotic. Then, perform catalase test, which should show a negative reaction for all Streptococci. S. pyogenes is cAMP test negative.

# Treatment
The treatment of choice is penicillin.  There is no reported instance of penicillin-resistance reported to date, although since 1985 there have been many reports of penicillin-tolerance.
Macrolides, chloramphenicol, and tetracyclines may be used if the strain isolated has been shown to be sensitive, but resistance is much more common.

# Antimicrobial therapy
- 1. Streptococcus pyogenes tonsilitis
- Preferred regimen (1): Penicillin V 250 mg PO bid or tid (for children) 250 mg PO qid or 500 mg PO bid (for adults) for 10 days
- Preferred regimen (2): Benzathine penicillin G if  27kg 1,200,000 U IM single-dose
- Alternative regimen (1): Amoxicillin 50 mg/kg/day PO qd for 10 days OR 25 mg/kg/day PO bid for 10 days. Its oral suspension is more tolerable to children and it is better absorbed by the GI tract
- Alternative regimen (2): first generation Cephalosporins are acceptable for treating recurrent group A streptococcus infection but not as first-line therapy
- Alternative regimen (3): Clarithromycin 250 mg PO bid for 10 days OR Azithromycin 12 mg/kg maximum 500 mg PO on day 1 THEN 6 mg/kg maximum 250 mg PO qd on days 2 through 5 OR Erythromycin 20 mg/kg/day PO or 40 mg/kg/day (ethylsuccinate) PO bid for 10 days.
- Alternative regimen (4): Clindamycin for penicillin-intolerant patients with erythromycin-resistant strains.
- Note: Intramuscular penicillin is the only therapy that has been shown to prevent initial attacks of rheumatic fever in controlled studies
- 2. Recurrent Streptococcus pyogenes tonsilitis
- Preferred regimen (1): Clindamycin 20-30 mg/kg/day PO tid (for children), 600 mg/day bid, tid or qid (for adults) for 10 days
- Preferred regimen (2): Amoxicillin-clavulanic acid 40 mg/kg/day PO tid (for children), 500 mg bid (for adults) for 10 days
- Alternative regimen: Benzathine penicillin G if 27kg 1,200,000 U IM single-dose  Rifampin 20 mg/kg/day PO bid for 4 days
- 3. Secondary prophylaxis for rheumatic fever
- Preferred regimen (1): Benzathine penicillin G if 27kg 1,200,000 U IM every 4 weeks
- Alternative regimen (1): Penicillin V potassium 250 mg PO bid
- Alternative regimen (2): Sulfadiazine if 27kg 1 g PO qd
- Duration of treatment: if residual cardiac disease, keep treatment until 40 patient is 40 years old or for 10 years (whichever is longer); if there's no residual cardiac disease keep treatment for 10 years or until age 21 years (whichever is longer); if there's rheumatic fever without carditis keep it for 5 years or until age 21 years (whichever is longer).
- Note: For patients allergic to penicillin and sulfadiazine, consider a macrolide or azalide antibiotic
- 4. Streptococcus pyogenes bacteremia
- Preferred regimen: Penicillin G 4 million units IV q4h AND Clindamycin 900 mg IV q8h for at least 14 days
- Penicillin is added to the regimen to cover any other group A streptococcus which might be resistant to Clindamycin.
- Alternative regimen (1): Erythromycin
- Alternative regimen (2): Azithromycin
- Alternative regimen (3): Clarithromycin
- Alternative regimen (4): any other -lactam
- Note (1): Macrolide resistance is increasing.
- Note (2): Consider using intravenous immune globulin in patients with invasive infection and signs of shock. Immunoglobulin-G IV 1 g/kg day 1, then 0.5 g/kg days 2 & 3.
- Note (3): If shock, administer massive IV fluids (10-20 L/day), Albumin if <2 g/dL, debridement of necrotic tissue.
- 5. Streptococcus pyogenes celulitis
- Preferred regimen: treat as Streptococcus pyogenes bacteremia
- 6 Epiglottitis in childern
- Preferred regimen (1): Cefotaxime 50 mg/kg IV q8h
- Preferred regimen (2): Ceftriaxone 50 mg/kg IV q24h
- Alternative regimen (1): Amoxicillin-SB 100200 mg/kg qd q6h
- Alternative regimen (2): Trimethoprim-Sulfamethoxazole 812 mg/kg bid
- Note: Have tracheostomy set at bedside. Chloro is effective, but potentially less toxic alternative agents available.
- 7 Burn wound sepsis
- Preferred regimen: Vancomycin 1 gm IV q12h AND (Amikacin 10 mg/kg IV loading dose then 7.5 mg/kg IV q12h) AND . Can use Piperacillin-Tazobactam if Piperacillin not available.
- 8. Soft tissue
- Note: For necrotizing fasciitis, surgical consultation for emergent fasciotomy and debridement; repeat debridements usually necessary.
- 9. Muscle
- Note: For myositis-debirdement is recommended.
- 10. Eye
- 10.1 Keratitis
- 10.1.1 Acute bacterial keratitis
- Preferred regimen: Moxifloxacin eye gtts. 1 gtt tid for 7 days
- Alternative therapy: Gatifloxacin eye gtts. 1-2 gtts q2h while awake for 2 days, then q4h for 3-7 days.
- Note: Prefer Moxifloxacin due to enhanced lipophilicity and penetration into aqueous humor (1 gtt = 1 drop).
- 10.1.2 Keratitis due to dry cornea, diabetes, immunosuppression
- Preferred regimen: Cefazolin (50 mg/mL) AND (Gentamicin OR Tobramycin (14 mg/mL) q1560 min around clock for  2472 hrs, then slow reduction)
- Alternative therapy: Vancomycin (50 mg/mL) AND Ceftazidime (50 mg/mL) q1560 min around clock for 2472 hrs, then slow reduction.
- Note: Specific therapy guided by results of alginate swab culture and sensitivity. Ciprofloxacin 0.3% found clinically equivalent to CefazolinAND Tobramycin; only concern was efficacy of Ciprofloxacin vs S. pneumoniae
- 10.2 Dacryocystitis (lacrimal sac)
- Preferred regimen: Moxifloxacin 1 gtt tid for 7 days OR Cefazolin (50 mg/mL) (1 gtt = 1 drop)
- 11. Suppurative phlebitis
- Preferred regimen: Vancomycin 15 mg/kg IV q12h (normal weight)
- Alternative regimen: Daptomycin 6 mg/kg IV q12h
- Note: Retrospective study for suppurative phlebitis recommends 2-3 weeks IV therapy and 2 weeks PO therapy.
- 12.  Infected prosthetic joint
- Preferred regimen: Penicillin G 2 million units IV q4h OR Ceftriaxone 2 g IV q24h for 4 weeks
- Note: Debridement & prosthesis retention with intravenous antibiotics.
- 13.  Hot tender parotid swelling
- Preferred regimen: Nafcillin OR Oxacillin 2 g IV q4h
- Note: Predisposing factors are stone(s) in Stensens duct, dehydration. Therapy depends on ID of specific etiologic organism.
- 14. Diabetic foot ulcer (ulcer with <2 cm of superficial inflammation)
- Preferred regimen: (Trimethoprim-Sulfamethoxazole 800/160 mg 1-2 tabs PO bid OR Minocycline 100 mg PO bid) AND (Penicillin VK 500 mg PO qid OR selected  Cephalosporins 2nd, 3rd generation - cefprozil 500 mg PO bid OR cefuroxime axetil 500 mg PO bid OR cefdinir 300 mg PO bid or 600 mg PO qd OR cefpodoxime 200 mg PO bid OR Fluoroquinolones Levofloxacin 750 mg PO qd).
- 15.  Recurrent cellulitis, chronic lymphedema prophylaxis
- Preferred regimen: Clindamycin 150 mg PO qd OR Trimethoprim-Sulfamethoxazole 800/160 mg 1 tablet PO qd OR stand-by therapy immediate treatment with Penicillin V OR Amoxicillin 500-750 mg PO bd at onset of symptoms.

# Prophylaxis
- Steptococcus Pyogenes (groups A Streptococcus) prophylaxis 
- Acute rheumatic fever prophylaxis
- Preferred regimen: Benzathine Penicillin 1.2 mu IM q mo, Penicillin V 250 mg PO bd, Erythromycin 250 mg PO bd until >5 yrs post-acute rheumatic fever and age in 20years.
- Recurrent cellulitis, chronic lymphedema prophylaxis
- Preferred regimen: Clindamycin 150 mg PO qd OR Trimethoprim-Sulfamethoxaole 1 DS PO qd OR stand-by therapy immediate treatment with Penicillin V OR Amoxicillin 500-750 mg PO bd at onset of symptoms.