Streptococcal Infections

Classification

Gram+ cocci, chains. Catalase-negative (vs Staph). Hemolysis: Alpha (partial, green), Beta (complete, clear), Gamma (none). Lancefield grouping (A-H, K-V): C-carbohydrate cell wall antigen, serological. S. pyogenes = Group A, beta-hemolytic. S. agalactiae = Group B, beta-hemolytic. Pneumococcus/viridans strep = alpha-hemolytic, UNGROUPABLE (no group carbohydrate). This topic = S. pyogenes focus. Viridans strep = see IE topic. Pneumococcus = see Respiratory topic.

S. pyogenes (GAS) Virulence Factors

M protein — MOST IMPORTANT. Antiphagocytic (blocks complement deposition). >200 M-types (antigenic variation) → type-specific immunity only, repeat infections possible. Also = rheumatic fever molecular mimicry antigen.

Hyaluronic acid capsule — antiphagocytic, chemically IDENTICAL to host connective tissue (molecular disguise, no Ab response).

Streptolysin O (oxygen-labile, immunogenic — ASO test basis) + Streptolysin S (oxygen-stable, non-immunogenic — visible beta-hemolysis, aerobic).

Spe A/B/C (streptococcal pyrogenic exotoxins) — superantigens, scarlet fever rash + strep TSS. Several PHAGE-ENCODED (lysogenic conversion).

Enzymes: Streptokinase (fibrinolysin, spread), Hyaluronidase (“spreading factor”), DNase/streptodornase (liquefies pus, aids spread), C5a peptidase (degrades C5a, blunts neutrophil recruitment).

Clinical Manifestations

Suppurative: Pharyngitis/tonsillitis (classic, sequelae > infection itself), Impetigo (honey-crusted, ±S.aureus), Erysipelas (sharp-demarcated, superficial, face/lower limb), Cellulitis (deeper, less sharp than erysipelas), NECROTIZING FASCIITIS (rapid spread, life-threatening, SURGICAL EMERGENCY — antibiotics alone insufficient, delayed debridement=↑mortality), Puerperal sepsis.

Toxin-mediated: Scarlet fever (pharyngitis + sandpaper rash, Spe toxin, no prior antitoxin immunity). Strep TSS (fever+hypotension+MOF, complicates invasive soft tissue infection).

Non-suppurative sequelae (IMMUNE-MEDIATED, post-acute-infection):

Acute rheumatic fever — see own topic. FOLLOWS PHARYNGITIS ONLY (essentially never skin infection)
Acute post-strep glomerulonephritis (PSGN) — follows PHARYNGITIS OR SKIN infection/impetigo. Type III hypersensitivity (immune complex GBM deposition)

Laboratory Diagnosis

Throat swab culture: beta-hemolytic colonies. Bacitracin sensitivity = presumptive test (Group A SENSITIVE, others RESISTANT). Definitive: latex agglutination (Lancefield) or PCR.

RADT (rapid antigen detection): GAS carbohydrate antigen, throat swab, minutes. High specificity, IMPERFECT sensitivity — negative RADT + suggestive clinical picture → back up with culture.

Serology (documents RECENT infection, NOT acute diagnosis — Ab takes weeks):

ASO titer — vs streptolysin O. Useful confirming preceding infection (rheumatic fever/PSGN workup)
Anti-DNase B — MORE RELIABLE after SKIN infection (ASO often stays low post-skin infection, streptolysin O inhibited by skin lipids). Better marker for PSGN-after-impetigo cases.

Treatment

Penicillin = 1st line for essentially ALL GAS infection. NOTABLY: S. pyogenes has NEVER developed clinically significant penicillin resistance (unlike most major pathogens). Erythromycin/clindamycin = penicillin allergy alternatives. Necrotizing fasciitis: emergency surgical debridement + high-dose IV antibiotics (penicillin+clindamycin — clindamycin added specifically to suppress TOXIN production via protein-synthesis inhibition, regardless of organism load).

S. agalactiae (GBS)

LEADING cause of neonatal sepsis+meningitis. Vertical transmission (colonized maternal genital tract, labor/delivery). Universal antenatal screening (vaginal-rectal swab, 35-37wk) + intrapartum antibiotic prophylaxis (IV penicillin during labor for colonized mothers) → substantially ↓early-onset neonatal GBS disease. Also: invasive disease in elderly + diabetics/chronic illness adults.

Classification

Streptococci are Gram-positive cocci arranged in chains (from division along a single plane), catalase-negative — the key test separating them from staphylococci. Two classification schemes matter, and both are needed together for full identification: haemolysis pattern on blood agar (alpha — partial, greenish; beta — complete, clear; gamma — none) and the Lancefield grouping (A through H, K through V — based on the C-carbohydrate cell-wall antigen, detected serologically). Streptococcus pyogenes (group A) and Streptococcus agalactiae (group B) are both beta-haemolytic; pneumococcus and viridans streptococci are alpha-haemolytic but ungroupable by the Lancefield scheme, since they lack the group-specific carbohydrate. This topic focuses on S. pyogenes as the dominant skin/soft-tissue pathogen in this section; viridans streptococci are covered under Infective Endocarditis, and pneumococcus under Infections of the Respiratory System.

Streptococcus pyogenes (Group A Streptococcus, GAS)

Virulence Factors

M protein — the single most important GAS virulence factor: a surface fibrillar protein that resists phagocytosis (by blocking complement deposition) and is highly antigenically variable (>200 M-types), which is why GAS infection confers only type-specific immunity and repeated GAS infections with different M-types are entirely possible across a lifetime. M protein is also the antigen implicated in rheumatic fever’s molecular mimicry (see Rheumatic Fever topic).
Hyaluronic acid capsule — further antiphagocytic, and chemically identical to host connective tissue hyaluronic acid, which is presumably why it doesn’t provoke an antibody response (molecular disguise).
Streptolysin O and S — pore-forming haemolysins; streptolysin O is oxygen-labile and strongly immunogenic (the basis of the ASO titre test), streptolysin S is oxygen-stable and non-immunogenic, responsible for the visible beta-haemolysis on aerobically incubated blood agar.
Streptococcal pyrogenic exotoxins (Spe A, B, C) — superantigens, responsible for scarlet fever’s rash and implicated in streptococcal toxic shock syndrome; several are phage-encoded (lysogenic conversion, as covered under Bacteriophage).
Enzymes: streptokinase (fibrinolysin, aids tissue spread), hyaluronidase (“spreading factor,” breaks down connective tissue hyaluronic acid), DNase (streptodornase, liquefies pus/necrotic debris, aiding spread through inflammatory exudate), and C5a peptidase (degrades the complement chemoattractant C5a, blunting neutrophil recruitment).

Clinical Manifestations

Suppurative (direct infection) syndromes: pharyngitis/tonsillitis (the classic entry-point infection, whose sequelae — rheumatic fever and post-streptococcal glomerulonephritis — carry far more long-term weight than the throat infection itself); impetigo (superficial, honey-crusted skin lesions, also caused by S. aureus); erysipelas (a sharply demarcated, raised, superficial skin infection, classically affecting the face or lower limb); cellulitis (deeper, less sharply demarcated than erysipelas, involving subcutaneous tissue); necrotizing fasciitis (a rapidly spreading, life-threatening deep soft-tissue infection destroying fascia and subcutaneous tissue — a true surgical emergency, since antibiotics alone cannot control it and delayed debridement is directly linked to mortality); and puerperal sepsis.

Toxin-mediated syndromes: scarlet fever (pharyngitis plus a diffuse, sandpaper-textured erythematous rash from Spe exotoxin, in a host lacking prior antitoxin immunity — the same organism causing plain pharyngitis in an immune host); streptococcal toxic shock syndrome (fever, hypotension, multi-organ failure, often complicating an invasive soft-tissue infection — mechanistically parallel to but epidemiologically distinct from staphylococcal TSS).

Non-suppurative sequelae — immune-mediated complications occurring after the acute infection has cleared, not from ongoing bacterial invasion: acute rheumatic fever (see its own topic — follows pharyngitis specifically, essentially never skin infection) and acute post-streptococcal glomerulonephritis (can follow either pharyngitis or skin infection/impetigo, from immune-complex deposition in the glomerular basement membrane — a type III hypersensitivity mechanism).

Laboratory Diagnosis

Throat swab culture: beta-haemolytic colonies on blood agar; bacitracin sensitivity is the classic presumptive test distinguishing group A (sensitive) from other beta-haemolytic streptococci (resistant); definitive grouping uses the latex agglutination Lancefield test or PCR.

Rapid antigen detection test (RADT): detects GAS group A carbohydrate antigen directly from a throat swab, giving a result in minutes — high specificity but imperfect sensitivity, so a negative RADT in a clinically suggestive case is generally backed up with culture.

Serology — used to document a recent streptococcal infection rather than to diagnose acute pharyngitis (antibody takes weeks to rise): ASO (antistreptolysin O) titre rises against streptolysin O, useful for confirming preceding infection when investigating suspected rheumatic fever or PSGN; anti-DNase B rises more reliably after skin infection (ASO titres often stay low after skin-only GAS infection, since streptolysin O is inhibited by skin lipids, making anti-DNase B the better serological marker in a PSGN case following impetigo rather than pharyngitis).

Treatment

Penicillin remains first-line for essentially all GAS infection — S. pyogenes has, notably, never developed clinically significant penicillin resistance despite decades of use, unlike most other major pathogens. Erythromycin/clindamycin serve as alternatives for penicillin allergy. Necrotizing fasciitis needs emergency surgical debridement alongside high-dose IV antibiotics (typically penicillin plus clindamycin, the latter added specifically to suppress toxin production regardless of organism load, via its protein-synthesis-inhibiting mechanism).

Streptococcus agalactiae (Group B Streptococcus, GBS)

A leading cause of neonatal sepsis and meningitis, acquired by vertical transmission from a colonized maternal genital tract during labour/delivery. Universal antenatal GBS screening (vaginal-rectal swab culture at 35–37 weeks) and intrapartum antibiotic prophylaxis (IV penicillin during labour for colonized mothers) have substantially reduced early-onset neonatal GBS disease incidence. Beyond neonates, GBS also causes invasive disease in the elderly and in adults with diabetes or other chronic illness.