Streptococcal Infections¶
Chapter 153 | Part 5: Infectious Diseases - Streptococcal Infections · Part 5 – Infectious Diseases: Bacterial · Chapter 153
Key Clinical Points¶
- Group A Streptococcus (GAS; S. pyogenes) is the primary cause of acute rheumatic fever (ARF) and poststreptococcal glomerulonephritis (PSGN).
- M protein on GAS surface binds plasma fibrinogen, inhibiting complement activation and phagocytic killing; M protein typing (emm gene) is the standard for serotyping.
- Streptococcal pharyngitis treatment (10-day penicillin) prevents ARF but does not prevent PSGN.
- Necrotizing fasciitis caused by GAS requires early surgical debridement plus high-dose penicillin and clindamycin (protein synthesis inhibitor).
- Streptococcal Toxic Shock Syndrome (TSS) requires isolation of GAS from a sterile site and clinical signs of severity (hypotension, organ dysfunction).
- Scarlet fever rash features: sandpaper-like texture, circumoral pallor, strawberry tongue, and Pastia's lines.
- Impetigo is superficial; cellulitis involves subcutaneous tissue; erysipelas involves superficial dermis with sharp demarcation.
- Macrolide resistance in invasive GAS isolates has risen to >30% in the US since 2021; avoid macrolides unless susceptibility is known.
- GBS (S. agalactiae) is a leading cause of neonatal sepsis and meningitis; Enterococci are now classified as a separate genus.
- Asymptomatic carriers of GAS may transmit infection; eradication is warranted if transmission occurs, but routine screening is not recommended.
1. DEFINITION & OVERVIEW¶
Streptococci are gram-positive cocci that form chains in liquid media. Most human pathogens are facultative anaerobes, though some are strict anaerobes. Identification relies on hemolytic patterns (β-hemolytic, α-hemolytic, γ-hemolytic), Lancefield grouping, and biochemical testing.
• Hemolytic Patterns: ◦ β-Hemolytic: Include Group A (S. pyogenes), Group B (S. agalactiae), and Groups C/G (S. dysgalactiae subsp. equisimilis). ◦ α-Hemolytic: Include S. pneumoniae and viridans group. ◦ Nonhemolytic: Include enterococci (now a separate genus) and anaerobes like Peptostreptococcus magnus.
1.1 Classification of Streptococci¶
• Group A Streptococcus (GAS; S. pyogenes): Causes pharyngitis, impetigo, cellulitis, scarlet fever, and postinfectior syndromes like ARF and PSGN. • Group B Streptococcus (GBS; S. agalactiae): Leading cause of neonatal sepsis, meningitis, and puerperal infection. • Viridans streptococci: Common causes of endocarditis, dental abscess, and brain abscess. • Enterococci: Formerly classified as group D streptococci; now a separate genus; common in UTI and nosocomial bacteremia.
• Table 153-1: Classification of Streptococci ◦ Lancefield Group A: S. pyogenes | β | Pharyngitis, impetigo, cellulitis, scarlet fever ◦ Lancefield Group B: S. agalactiae | β | Neonatal sepsis and meningitis, puerperal infection ◦ Lancefield Group C, G: S. dysgalactiae subsp. equisimilis | β | Cellulitis, bacteremia, endocarditis ◦ Lancefield Group D: Enterococcus faecalis/faecium | Usually nonhemolytic | Urinary tract infection, nosocomial bacteremia ◦ Variable or nongroupable: Viridans streptococci (S. sanguis, S. mitis) | α | Endocarditis, dental abscess, brain abscess ◦ Variable or nongroupable: Intermedius or milleri group (S. intermedius, S. anginosus, S. constellatus) | Variable | Brain abscess, visceral abscess ◦ Variable or nongroupable: Anaerobic streptococci (Peptostreptococcus magnus) | Usually nonhemolytic | Sinusitis, pneumonia, empyema, brain abscess, liver abscess
2. EPIDEMIOLOGY¶
• Trends: GAS infections declined during 2020–2022 due to social distancing but rebounded in 2022–2024, with increased severe cases (pneumonia, necrotizing fasciitis). ◦ M1 GAS strains linked to scarlet fever outbreaks.
• Global Burden: Rheumatic heart disease (RHD) prevalence is significantly higher in low-resource countries. ◦ Incidence of GAS infections and RHD is 10× higher in low-income countries compared to developed nations (Figure 153-1).
2.1 Global Burden of Rheumatic Heart Disease¶
• Regional Variation: Highest rates of RHD are found in sub-Saharan Africa and South Asia.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
GAS virulence factors include M protein, hyaluronic acid capsule, and exotoxins.
• M Protein: ◦ Binds fibrinogen → inhibits complement activation and phagocytic killing. ◦ Serotyping: Based on emm gene sequencing (200+ types identified). ◦ Immunity: Antibodies to specific M types confer immunity against homologous strains.
• Capsule: ◦ Composed of hyaluronic acid; mimics host tissue → evades phagocytosis. ◦ Note: Acapsular strains can still cause disease.
• Exotoxins: ◦ Pyrogenic exotoxins (A–G): Cause scarlet fever rash and TSS. ◦ Streptolysin O and S: Damage cell membranes. ◦ DNase B and SpyCEP: Inhibit neutrophil recruitment.
3.1 M Protein and Serotyping¶
Definition (Harrison's 22e): The major surface protein of GAS, M protein, is the basis for serotyping using specific antisera or emm gene sequencing.
• Structure: Fibrillar, anchored in cell wall; variable N-terminal region determines antigenic type. ◦ Methodology: emm typing (PCR-based) has replaced traditional serotyping due to higher sensitivity and availability of CDC databases.
3.2 Virulence Factors¶
Definition (Harrison's 22e): The cell wall carbohydrate antigen (group A antigen) is used for definitive identification of S. pyogenes.
• Note: Group A antigen may occasionally be present in S. dysgalactiae subsp. equisimilis, which typically expresses group C/G antigens.
4. CLINICAL FEATURES¶
• Pharyngitis: Most common in children aged 5–15 years. ◦ Symptoms: Sore throat, fever, and tender anterior cervical lymphadenopathy.
• Scarlet Fever: ◦ Appearance: Day 1–2 (upper trunk); Day 3–5 (extremities). ◦ Features: Sandpaper-like texture, circumoral pallor, strawberry tongue, and Pastia's lines. ◦ Desquamation: Occurs on palms/soles after 6–9 days.
• Skin Infections: ◦ Impetigo: Superficial infection; characterized by honey-colored crusts (Figure 153-3). ◦ Erysipelas: Superficial dermis; well-demarcated, erythematous, edematous, warm plaques (Figure 153-4). ◦ Cellulitis: Subcutaneous tissue; non-specific redness.
• Deep Tissue Infections: ◦ Necrotizing Fasciitis: Severe pain, dusky erythema, rapid progression. GAS involved in ~60% of cases. ◦ Streptococcal TSS: Fever, hypotension, multiorgan failure (renal impairment, thrombocytopenia).
4.1 Pharyngitis¶
• Differential Diagnosis: ◦ Viral: Rhinovirus, adenovirus. ◦ Bacterial: Arcanobacterium haemolyticum, Neisseria gonorrhoeae.
• Table 153-2: Infectious Etiologies of Acute Pharyngitis ◦ Rhinovirus → Common cold ◦ Adenovirus → Pharyngoconjunctival fever ◦ Parainfluenza virus → Cold, croup ◦ Herpes simplex virus → Gingivostomatitis (primary infection) ◦ Other agents: Coronavirus, Coxsackievirus, EBV, CMV, HIV.
4.2 Scarlet Fever¶
Definition (Harrison's 22e): Scarlet fever is streptococcal pharyngitis accompanied by a characteristic rash caused by pyrogenic exotoxins.
• Clinical Progression: ◦ Day 1–2: Upper trunk. ◦ Day 3–5: Extremities. ◦ Day 6–9: Desquamation on palms/soles.
4.3 Skin and Soft Tissue Infections¶
• Impetigo: Superficial infection; honey-colored crusts. Bullous impetigo (S. aureus) differs by thin paper-like crusts. • Erysipelas: Well-demarcated erythematous plaques. • Cellulitis: Non-specific redness.
4.4 Deep Soft Tissue Infections¶
• Necrotizing Fasciitis: Severe pain, dusky erythema, rapid progression; requires surgical debridement + high-dose penicillin and clindamycin. • Streptococcal TSS: Hypotension, multiorgan failure.
• Table 153-4: Case Definition for Streptococcal Toxic Shock Syndrome ◦ I. Isolation of group A streptococci (S. pyogenes) from a normally sterile site OR a nonsterile site. ◦ II. Clinical signs of severity: ◦ A. Hypotension. ◦ B. ≥2 of the following: 1. Renal impairment, 2. Coagulopathy, 3. Liver function impairment, 4. ARDS, 5. Generalized erythematous macular rash (may desquamate), 6. Soft tissue necrosis (including necrotizing fasciitis or myositis) or gangrene.
4.5 Bacteremia, Puerperal Sepsis, and Streptococcal Toxic Shock¶
• Bacteremia: May occur without focal infection in children. ◦ Puerperal Sepsis: Now more commonly caused by GBS than GAS.
• Clinical Parameters (Summary): ◦ WBC: Leukocytosis with left shift. ◦ Calcium: Hypocalcemia (<7.5 mg/dL). ◦ Albumin: Hypoalbuminemia (<3 g/dL).
5. DIFFERENTIAL DIAGNOSIS¶
• Scarlet Fever: Must be differentiated from measles, Kawasaki disease, and toxic shock syndrome.
• Pharyngitis: ◦ Viral: Adenovirus, EBV. ◦ Bacterial: Arcanobacterium haemolyticum, gonococcal pharyngitis.
6. INVESTIGATIONS & DIAGNOSIS¶
• Gold Standard: Throat culture for streptococcal pharyngitis. • Rapid Testing: Rapid antigen detection tests (RADTs) have ≈90% sensitivity. • Serology: ASO and DNase B titers used for ARF/PSGN diagnosis.
6.1 Diagnostic Algorithm¶
- Clinical Evaluation: Assess for sore throat, fever, and exudate.
- Primary Testing: Perform throat culture or RADT.
- Decision Branch (Pharyngitis): If positive → Initiate 10-day penicillin therapy.
- Decision Branch (Suspected ARF/PSGN): If culture/RADT negative but ARF/PSGN suspected → Perform serologic tests (ASO, DNase B titers).
7. MANAGEMENT & TREATMENT¶
-
Pharyngitis: ◦ Penicillin V: 250 mg PO q6h for 10 days. ◦ Amoxicillin: 500 mg PO q8h for 10 days. ◦ Note: Macrolides contraindicated in >30% of invasive GAS isolates; avoid unless susceptibility is known.
-
Necrotizing Fasciitis: ◦ Step 1: Immediate surgical debridement. ◦ Step 2: IV penicillin G (24 million units/day). ◦ Step 3: Clindamycin (900 mg IV q8h) if susceptible; Linezolid (600 mg IV q12h) if clindamycin-resistant.
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Scarlet Fever: ◦ Treatment same as pharyngitis.
-
Erysipelas/Cellulitis: ◦ Severe: Penicillin G (1–2 mU IV q4h). ◦ Mild to moderate: Procaine penicillin (1.2 mU IM bid).
-
Pneumonia/Empyema: ◦ Penicillin G (2–4 mU IV q4h) plus drainage of empyema.
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Asymptomatic Pharyngeal Colonization: ◦ Eradication only if transmission occurs; otherwise, no treatment indicated.
7.1 Treatment of Group A Streptococcal Infections¶
• Penicillin V: 250 mg PO q6h for 10 days • Amoxicillin: 500 mg PO q8h for 10 days • Clindamycin: 900 mg IV q8h (for necrotizing fasciitis) • Linezolid: 600 mg IV q12h (if clindamycin-resistant)
8. PROGNOSIS & COMPLICATIONS¶
• Suppurative Complications: ◦ Abscesses, cellulitis spread, and lymphadenopathy.
• Nonsuppurative Complications: ◦ Acute Rheumatic Fever (ARF): 1–3% of GAS pharyngitis. ◦ Poststreptococcal Glomerulonephritis (PSGN): 0.5–2%. ◦ Rheumatic Heart Disease: Leading cause of preventable cardiovascular death in children.
8.1 Suppurative Complications¶
Untreated GAS infections commonly lead to abscess formation, cellulitis spread, and lymphadenopathy.
8.2 Nonsuppurative Complications¶
Definition (Harrison's 22e): Acute rheumatic fever is an autoimmune sequelae of S. pyogenes infection, characterized by carditis, arthritis, and chorea.
9. SPECIAL CONSIDERATIONS¶
• Pregnancy: ◦ GBS screening: 35–37 weeks gestation. ◦ Intrapartum prophylaxis: Ampicillin or cefazolin if positive.
• Prevention: ◦ Vaccines for GAS under development. ◦ Prophylaxis with penicillin in ARF/PSGN patients.
9.1 Prevention¶
Asymptomatic GAS carriers: Treat only if transmission occurs. GBS screening in pregnancy is standard practice.
10. KEY PEARLS & CLINICAL TRAPS¶
• Scarlet Fever: Rash spares palms/soles; Pastia's lines are key diagnostic features. • Necrotizing Fasciitis: Requires immediate surgery + IV penicillin/clindamycin. • Macrolide Resistance: >30% in invasive GAS isolates in US; avoid empiric use. • TSS Diagnosis: Requires GAS isolation from a sterile site and clinical signs of shock (hypotension, organ dysfunction).
Reference Tables¶
TABLE 153-1 Classification of Streptococci¶
Harrison's 22e, p.1206
| LANCEFIELD GROUP |
REPRESENTATIVE SPECIES | HEMOLYTIC PATTERN | TYPICAL INFECTIONS |
|---|---|---|---|
| A | S. pyogenes | β | Pharyngitis, impetigo, cellulitis, scarlet fever |
| S. agalactiae | β | ||
| C, G | S. dysgalactiae subsp. equisimilis | β | Cellulitis, bacteremia, endocarditis |
| Enterococcia: E. faecalis, E. faecium | Usually nonhemolytic | ||
| Nonenterococci: S. gallolyticus (formerly S. bovis) | Usually nonhemolytic | ||
| Variable or nongroupable |
Viridans streptococci: S. sanguis, S. mitis | α | Endocarditis, dental abscess, brain abscess |
| Intermedius or milleri group: S. intermedius, S. anginosus, S. constellatus |
Variable | Brain abscess, visceral abscess | |
| Anaerobic streptococcib: Peptostreptococcus magnus |
Usually nonhemolytic | Sinusitis, pneumonia, empyema, brain abscess, liver abscess |
TABLE 153-2 Infectious Etiologies of Acute Pharyngitis ORGANISM Viruses Rhinovirus Coronavirus Adenovirus Influenza…¶
Harrison's 22e, p.1208
| ORGANISM | ASSOCIATED CLINICAL SYNDROME(S) |
|---|---|
| Viruses | |
| Rhinovirus | Common cold |
| Adenovirus | Pharyngoconjunctival fever |
| Parainfluenza virus | Cold, croup |
| Herpes simplex virus | Gingivostomatitis (primary infection) |
TABLE 153-3 Treatment of Group A Streptococcal Infections INFECTION Pharyngitis¶
Harrison's 22e, p.1208
| INFECTION | TREATMENTa |
|---|---|
| Pharyngitis | Benzathine penicillin G (1.2 mU IM) or penicillin V (250 mg PO tid or 500 mg PO bid) × 10 days |
| (Children <27 kg: Benzathine penicillin G [600,000 units IM] or penicillin V [250 mg PO bid or tid] × 10 days) |
|
| Cytomegalovirus | Mononucleosis-like syndrome |
| Bacteria | |
| Group A streptococci | Pharyngitis, scarlet fever |
| Mixed anaerobes | Vincent’s angina |
| Erysipelas/cellulitis | Severe: Penicillin G (1–2 mU IV q4h) |
| Mild to moderate: Procaine penicillin (1.2 mU IM bid) | |
| Neisseria gonorrhoeae | Pharyngitis |
| Pneumonia/empyema | Penicillin G (2–4 mU IV q4h) plus drainage of empyema |
| Francisella tularensis | Pharyngeal tularemia |
| Yersinia enterocolitica | Pharyngitis, enterocolitis |
| Chlamydiae | |
| Chlamydia psittaci | Psittacosis |
| Mycoplasma pneumoniae | Bronchitis, pneumonia |
TABLE 153-4 Case Definition for Streptococcal Toxic Shock Syndrome a I. Isolation of group A streptococci (…¶
Harrison's 22e, p.1212
- I. Isolation of group A streptococci (Streptococcus pyogenes)
A. From a normally sterile site
B. From a nonsterile site
II. Clinical signs of severity
A. Hypotension and
B. ≥2 of the following signs
1. Renal impairment
2. Coagulopathy
3. Liver function impairment
4. Adult respiratory distress syndrome
5. A generalized erythematous macular rash that may desquamate
6. Soft tissue necrosis, including necrotizing fasciitis or myositis; or
gangrene