Streptococcus & Enterococcus

Gram-positive cocci in chains/pairs that are catalase-negative — the single best test separating them from staphylococci. This topic is a perennial favourite for NEET PG because it cleanly integrates classification (Lancefield, haemolysis), virulence factors, post-infectious immune sequelae, and laboratory identification (optochin, bacitracin, bile-aesculin, CAMP). Master the small "discriminator" tests and you can answer almost any single-best-answer item here.

Classification — the three overlapping schemes

Streptococci are classified by three independent systems that exam-setters love to cross over each other:

1. Haemolysis on blood agar — alpha (partial/green), beta (complete/clear), gamma (none).
2. Lancefield grouping — based on the cell-wall C carbohydrate antigen (groups A–V).
3. Biochemical/physiological tests — optochin, bacitracin, bile solubility, bile-aesculin, growth in 6.5% NaCl.

Organism	Haemolysis	Lancefield	Key discriminator
S. pyogenes	Beta	A	Bacitracin sensitive, PYR positive
S. agalactiae	Beta	B	CAMP positive, hippurate hydrolysis, bacitracin resistant
S. pneumoniae	Alpha	None (ungroupable)	Optochin sensitive, bile soluble
Viridans group	Alpha	Variable/none	Optochin resistant, bile insoluble
Enterococcus (E. faecalis/faecium)	Gamma (variable)	D	Bile-aesculin +, grows in 6.5% NaCl, PYR +
S. bovis (gallolyticus)	Gamma	D	Bile-aesculin +, NO growth in 6.5% NaCl

High-yield: The classic exam discriminator — both Enterococcus and S. bovis are bile-aesculin positive (group D), but only Enterococcus grows in 6.5% NaCl. This single fact separates the two most-confused group D organisms.

High-yield: Catalase test separates Streptococcus/Enterococcus (negative) from Staphylococcus (positive). PYR test is positive for S. pyogenes and Enterococcus — both are PYR positive, a frequent trick.

Streptococcus pyogenes (Group A Streptococcus, GAS)

Virulence factors

The exam centres on M protein and the toxins.

• M protein — the major virulence factor. Anti-phagocytic (inhibits complement C3b deposition), basis of >100 serotypes (Griffith typing), and the antigen that shares epitopes with human myocardium → molecular mimicry in rheumatic fever. M protein also binds factor H.
• Hyaluronic acid capsule — non-immunogenic (mimics host tissue), anti-phagocytic.
• Streptolysin O (SLO) — oxygen-labile, antigenic → basis of ASO titre. Cardiotoxic.
• Streptolysin S — oxygen-stable, non-antigenic, responsible for surface (plate) beta-haemolysis.
• Streptococcal pyrogenic exotoxins (SPE-A, B, C) — superantigens; cause the rash of scarlet fever and streptococcal toxic shock syndrome (STSS). SPE-A/C are phage-encoded; SPE-B is a potent protease implicated in necrotising fasciitis.
• Streptokinase (fibrinolysin), DNase B (anti-DNase B is the best serological marker for skin/pyoderma-associated GAS), hyaluronidase ("spreading factor"), C5a peptidase.

High-yield: ASO titre rises after pharyngeal infection; anti-DNase B is more reliable after skin (pyoderma) infection because lipids in skin neutralise streptolysin O, blunting the ASO response. This is the favourite PSGN-following-pyoderma question.

Clinical syndromes (three buckets)

1. Suppurative/local: pharyngitis (commonest), pyoderma/impetigo, erysipelas, cellulitis, necrotising fasciitis (type II), puerperal sepsis.
2. Toxin-mediated: scarlet fever, streptococcal toxic shock syndrome.
3. Non-suppurative (post-infectious immune) sequelae: acute rheumatic fever (ARF) and post-streptococcal glomerulonephritis (PSGN).

Scarlet fever — sandpaper rash, circumoral pallor, strawberry tongue (white → red), Pastia lines (linear petechiae in skin folds), desquamation. Dick test historically tested susceptibility (positive = susceptible). Schultz–Charlton reaction = rash blanching on injecting antitoxin.

Post-streptococcal sequelae — the most-tested comparison

Feature	Acute Rheumatic Fever	PSGN
Preceding infection	Pharyngitis only	Pharyngitis or skin (pyoderma)
Latent period	1–5 weeks (~3 wk)	1–2 wk (pharyngitis), 3–6 wk (skin)
Mechanism	Type II hypersensitivity, molecular mimicry (M protein vs myosin)	Type III, immune-complex deposition
Nephritogenic/rheumatogenic strains	M types 1,3,5,6,18	M types 12 (throat), 49 (skin)
Recurrence with reinfection	Yes — needs prophylaxis	No — does not recur
Prognosis	Chronic valvular damage (mitral)	Usually self-limiting, good in children

High-yield: Rheumatic fever NEVER follows skin infection — only pharyngitis. PSGN can follow either. Rheumatic fever recurs (hence long-term penicillin prophylaxis); PSGN does not recur.

Jones criteria (revised) for ARF — diagnosis needs 2 major OR 1 major + 2 minor, PLUS evidence of preceding strep infection.

• Major (mnemonic JONES): Joints (migratory polyarthritis), O = ♥ (carditis), Nodules (subcutaneous), Erythema marginatum, Sydenham chorea.
• Minor: fever, arthralgia, raised ESR/CRP, prolonged PR interval.

High-yield: Carditis is the only manifestation that causes permanent damage (chronic rheumatic heart disease, classically mitral stenosis). Sydenham chorea can be the sole manifestation and may appear months later with negative ASO.

Diagnosis & management of GAS

• Throat swab culture on blood agar = gold standard; rapid antigen detection test (RADT) is specific but a negative needs culture confirmation in children.
• Drug of choice: Penicillin (penicillin V orally, or single IM benzathine penicillin). No documented penicillin resistance in S. pyogenes. Macrolide for penicillin-allergic (note rising macrolide resistance).
• Necrotising fasciitis / STSS: surgical debridement + penicillin PLUS clindamycin (clindamycin = "Eagle effect", suppresses toxin synthesis at the ribosome) ± IVIG.
• Secondary prophylaxis (ARF): benzathine penicillin G IM every 3–4 weeks. Duration depends on carditis severity (no carditis ~5 yr; carditis with residual valve disease into adulthood).

Streptococcus agalactiae (Group B Streptococcus, GBS)

• CAMP test positive (synergistic arrowhead haemolysis with S. aureus beta-toxin), hippurate hydrolysis positive, bacitracin resistant.
• Colonises maternal genital/GI tract. Leading cause of neonatal sepsis and meningitis.

Early-onset (<7 days): vertical, presents as pneumonia/sepsis. Late-onset (7 days–3 months): meningitis, often nosocomial/horizontal.

High-yield: Intrapartum ampicillin/penicillin prophylaxis is given to mothers screened GBS-positive at 35–37 weeks rectovaginal swab. Treatment of neonatal disease = ampicillin + gentamicin.

Streptococcus pneumoniae (pneumococcus)

• Lancet-shaped, Gram-positive diplococci, alpha-haemolytic.
• Optochin sensitive (zone ≥14 mm with 5-µg disc) and bile soluble — the two tests that distinguish it from viridans streptococci.
• Polysaccharide capsule = chief virulence factor; basis of Quellung (Neufeld) reaction (capsular swelling with type-specific antiserum) and of the vaccines. Over 90 serotypes.

Diseases: commonest cause of community-acquired pneumonia (lobar), bacterial meningitis in adults, otitis media and sinusitis in children, and most common organism in post-splenectomy/sickle-cell sepsis (OPSI).

High-yield: Optochin sensitive + bile soluble = S. pneumoniae; optochin resistant + bile insoluble = viridans group. Asplenic and sickle-cell patients are uniquely vulnerable to encapsulated organisms — pneumococcus tops the list.

Lab flow: Alpha-haemolytic colony with central depression (draughtsman/carrom-coin colony) → optochin disc → sensitive → bile solubility confirms → Quellung for serotyping.

Vaccines: PCV13/PCV15/PCV20 (conjugate, T-cell dependent, given to infants) and PPSV23 (polysaccharide, T-independent, for adults ≥65 and high-risk). Drug of choice: penicillin/amoxicillin for sensitive strains; ceftriaxone + vancomycin empirically for pneumococcal meningitis pending sensitivities (penicillin resistance via altered PBPs).

Viridans streptococci

A heterogeneous alpha-haemolytic group (S. mitis, S. sanguinis, S. mutans, S. salivarius, S. anginosus/milleri group). Normal oral/GI flora.

• S. mutans → dental caries.
• S. sanguinis/mitis → subacute bacterial endocarditis on previously damaged valves (low-virulence, after dental procedures).
• S. anginosus (milleri) group → pyogenic abscesses (brain, liver).
• S. gallolyticus (bovis) endocarditis/bacteraemia is strongly associated with colonic carcinoma — warrants colonoscopy.

High-yield: Optochin-resistant, bile-insoluble alpha-haemolytic streptococcus from a patient with subacute endocarditis after dental work = viridans group. S. bovis bacteraemia → look for colon cancer.

Enterococcus (E. faecalis, E. faecium)

Formerly group D streptococci, now a separate genus. Extremely hardy: survive bile, 6.5% NaCl, pH 9.6, 10–45°C, and brief heating (60°C/30 min).

• Bile-aesculin positive, PYR positive, grow in 6.5% NaCl (distinguishes from S. bovis).
• E. faecalis is commonest overall; E. faecium is more drug-resistant.
• Cause UTI, biliary/intra-abdominal sepsis, endocarditis, and nosocomial bacteraemia (catheter/line-related).

Intrinsic & acquired resistance — VRE

Enterococci are intrinsically resistant to cephalosporins, low-dose aminoglycosides (need synergy with cell-wall agent), clindamycin, and TMP-SMX (in vivo). They acquire high-level aminoglycoside and vancomycin resistance.

VRE gene	Phenotype	Notes
vanA	High-level resistance to vancomycin and teicoplanin	Most common, transposon Tn1546, plasmid-borne (transferable to MRSA risk)
vanB	Vancomycin resistant, teicoplanin sensitive	Variable level
vanC	Low-level, intrinsic	E. gallinarum/casseliflavus

High-yield: Vancomycin resistance is due to replacement of the terminal D-alanyl-D-alanine of peptidoglycan precursor with D-alanyl-D-lactate, drastically reducing vancomycin binding. vanA = resistant to both vancomycin and teicoplanin; vanB = teicoplanin sensitive.

Treatment: ampicillin (faecalis) ± gentamicin synergy for endocarditis. For VRE: linezolid or daptomycin; quinupristin-dalfopristin works against E. faecium (not faecalis), tigecycline as alternative.

Investigation of choice — quick mapping

• Strep throat: throat swab culture (gold standard) / RADT.
• ARF: Jones criteria + ASO/anti-DNase B.
• Pneumococcal pneumonia: sputum Gram stain + culture; urinary pneumococcal antigen; blood culture if severe.
• Endocarditis: three sets of blood cultures + transthoracic/transoesophageal echo (Duke criteria).
• Pneumococcal serotyping: Quellung reaction.

Complications

• GAS: rheumatic heart disease (mitral stenosis), chronic kidney disease post-PSGN (rare in children), STSS multi-organ failure, limb loss in necrotising fasciitis.
• Pneumococcus: empyema, lung abscess, meningitis with deafness, OPSI in asplenics.
• Enterococcus: relapsing endocarditis, untreatable VRE bacteraemia, vanA transfer to S. aureus (VRSA).

Key differentials & confusion-busters

• GAS vs GBS beta-haemolytic: bacitracin (A sensitive) and CAMP (B positive).
• Pneumococcus vs viridans: optochin + bile solubility.
• Enterococcus vs S. bovis: 6.5% NaCl growth.
• Strep vs Staph: catalase.
• Strep vs Aerococcus/Leuconostoc (vanco-resistant lookalikes): Leuconostoc/Pediococcus are intrinsically vancomycin resistant gram-positive cocci — a sneaky distractor for VRE.

Recently asked / exam angle

• "Bile-aesculin positive, grows in 6.5% NaCl, PYR positive" → Enterococcus.
• "Subacute endocarditis after dental extraction, optochin resistant" → viridans (S. sanguinis).
• "D-Ala-D-Ala replaced by D-Ala-D-Lactate" → vanA vancomycin resistance.
• Clindamycin added to penicillin in necrotising fasciitis → toxin suppression (Eagle effect).
• ASO low but glomerulonephritis after skin infection → check anti-DNase B.
• Rheumatic fever does NOT follow pyoderma → only pharyngitis.
• S. bovis bacteraemia → screen for colon carcinoma.
• Quellung reaction → capsular swelling, S. pneumoniae serotyping.
• Mitral stenosis as the classic chronic valve lesion of RHD.

Rapid revision

1. All strep/enterococci are catalase-negative; Staph is catalase-positive.
2. S. pyogenes: bacitracin sensitive, PYR positive, beta-haemolytic, group A.
3. M protein = chief virulence factor of GAS (anti-phagocytic + mimicry).
4. ASO for throat, anti-DNase B for skin GAS infection.
5. Rheumatic fever follows pharyngitis only; PSGN follows throat or skin.
6. Jones: carditis is the only manifestation leaving permanent damage → mitral stenosis.
7. GBS = CAMP positive, hippurate positive, neonatal sepsis/meningitis; intrapartum penicillin.
8. Pneumococcus: optochin sensitive + bile soluble; Quellung for capsule; OPSI in asplenics.
9. Viridans: optochin resistant + bile insoluble; subacute endocarditis; S. bovis → colon cancer.
10. Enterococcus: bile-aesculin +, 6.5% NaCl +, PYR +; intrinsically cephalosporin-resistant.
11. vanA = vanco + teico resistant; vanB = teico sensitive; mechanism = D-Ala-D-Lac.
12. VRE drugs: linezolid, daptomycin; quinupristin-dalfopristin for E. faecium only.