Staph vs Strep — Bone Wizardry

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Before We Start

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Gram stain comes back: gram-positive cocci. That's all you know. Time to figure out what you're dealing with.

Quick — what's the FIRST test you run to split Staph from Strep?

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The Big Split — Catalase Test

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Every gram-positive cocci question on boards starts here. One test. Two families. Done.

💡 Drop hydrogen peroxide (H₂O₂)H2O2 is toxic to bacteria. Catalase breaks it down: 2 H2O2 → 2 H2O + O2. The O2 is what makes the bubbles. If your bacteria can defend against H2O2, they have catalase → Staph. on the colony. Bubbles? That's Staph (catalase positive). No bubbles? That's Strep (catalase negative).

WHY: Staph produces the enzyme catalase, which breaks down H₂O₂ into water + oxygen. The oxygen is what makes the fizzy bubbles. Strep can't do this.

🔑 CATalase = staph. Cats are independent loners (clusters). Dogs chain together on walks (strep chains). Cats = catalase.

On Gram stain, you can also see the difference:

Staphylococcus

Arrangement: CLUSTERS (grape-like)

Catalase: POSITIVE (bubbles)

Think: Grapes at a party

Streptococcus

Arrangement: C H A I N S (conga line)

Catalase: NEGATIVE (nothing happens)

Think: Conga line at a party

🔑 Staph clusters like grapes at a party. Strep chains like a conga line. Same party, very different energy.

You add H₂O₂ to a colony of gram-positive cocci. Nothing happens. No bubbles. What organism family is this?

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The Staph Family — Coagulase Sorts Them

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You know it's Staph (catalase positive, clusters). Now what? The next test is coagulase.

🔥 CoagulaseCoagulase converts fibrinogen → fibrin, forming a clot around the bacteria. This is a virulence factor — the clot protects the bacteria from phagocytosis. Only S. aureus is coagulase positive. It literally shields itself with your own clotting system. positive? That's S. aureus — the only coagulase-positive Staph. Everything else is CoNSCoagulase-Negative Staphylococci. The main two are S. epidermidis and S. saprophyticus. Less virulent than aureus, but still clinically important. (coagulase-negative staph).

Meet the family:

Organism	Coagulase	Key Feature	Diseases
S. aureus	POSITIVE	Golden pigment, most virulent	Skin infections, endocarditis, osteomyelitis, food poisoning, MRSA
S. epidermidis	Negative	Biofilm on prosthetics, novobiocin sensitiveThis is how you tell epidermidis from saprophyticus. Epidermidis is SENSITIVE to novobiocin (killed by it). Saprophyticus is RESISTANT. This is a pure board fact — novobiocin is rarely used clinically.	Prosthetic valve endocarditis, catheter infections, joint replacements
S. saprophyticus	Negative	Novobiocin RESISTANT	UTIs in young sexually active women (2nd after E. coli)

🔑 S. aureus = gold standard of infection. Aureus = Au (gold on the periodic table). Golden color, golden virulence — it does everything and does it aggressively.

⚠ Board Trap: S. epidermidis vs S. saprophyticus

Both are coagulase-negative. Both are low-virulence. The board question will give you a young woman with a UTI and a coagulase-negative staph — that's S. saprophyticus. Or it'll give you a prosthetic valve infection with a coagulase-negative staph — that's S. epidermidis.

Lab differentiator: Novobiocin. Epidermidis = Sensitive. Saprophyticus = Resistant.
Mnemonic: Saph is Resistant. No wait — Saprophyticus has R for Resistant. Epidermidis is Sensitive. ER, ES. "sapER, epidES." (Or just remember: the UTI one resists.)

A 22-year-old sexually active woman has dysuria and frequency. Urine culture grows coagulase-negative, novobiocin-resistant gram-positive cocci in clusters. What's the organism?

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The Strep Family — Hemolysis Sorts Them

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Catalase negative, chains on Gram stain. It's Strep. Now you look at hemolysis pattern on a blood agar plate.

💡 Three patterns: Beta (complete lysis — clear zone), Alpha (partial lysis — green zone), Gamma (no lysis — nothing happens).

BETA-hemolytic Strep (complete destruction):

Group A — S. pyogenes

Hemolysis: Beta

Key test: Bacitracin SENSITIVE

Diseases: Pharyngitis, scarlet fever, necrotizing fasciitis"Flesh-eating bacteria." S. pyogenes produces exotoxins and proteases that destroy tissue rapidly. Surgical emergency — antibiotics alone won't save the patient., rheumatic feverAutoimmune reaction weeks after strep pharyngitis. Anti-streptococcal antibodies cross-react with cardiac tissue (molecular mimicry). Causes pancarditis. Jones criteria for diagnosis. This does NOT happen after skin infections — only pharyngitis., post-strep glomerulonephritisImmune complex deposition in glomeruli 1-3 weeks after strep infection (pharyngitis OR skin). Type III hypersensitivity. Hematuria, proteinuria, edema, hypertension. Unlike rheumatic fever, PSGN CAN follow skin infections.

Group B — S. agalactiae

Hemolysis: Beta

Key test: Bacitracin RESISTANT

Diseases: Neonatal meningitis/sepsisGBS colonizes the vaginal canal. During delivery, the baby gets exposed. Neonates have immature immune systems → meningitis, pneumonia, sepsis. This is why we screen pregnant women at 35-37 weeks and give intrapartum penicillin if positive., pregnant women screened at 35-37 weeks

⚠ Board Trap: Group A vs Group B — Both are Beta!

Both are beta-hemolytic. The board WILL try to confuse you. The differentiator is bacitracin.

• Group A = bacitracin sensitive (A is Affected by bacitracin)
• Group B = bacitracin resistant (B says "Bye, that doesn't work on me")

Clinical context matters too: pharyngitis + scarlet fever = A. Neonatal sepsis + pregnant woman = B.

ALPHA-hemolytic Strep (partial — green zone):

S. pneumoniae

Hemolysis: Alpha (green zone)

Key test: Optochin SENSITIVE

Morphology: Lancet-shaped diplococci

Other: Quellung reaction positiveAdd anticapsular antibodies to the bacteria. If it has a capsule (pneumococcus does), the capsule swells visibly under microscopy. "Quellung" = German for "swelling." The capsule is its main virulence factor — prevents phagocytosis., bile soluble

Diseases: #1 bacterial meningitis (adults), #1 bacterial pneumonia, otitis media, sinusitis

Viridans Group Strep

Hemolysis: Alpha (green zone)

Key test: Optochin RESISTANT

Morphology: No special shape

Other: Normal dental flora, bile insoluble

Diseases: Subacute endocarditisViridans strep are dental flora. After dental procedures, they enter the bloodstream and settle on PREVIOUSLY DAMAGED valves (rheumatic, prosthetic). Subacute onset over weeks-months with low-grade fever, unlike the acute fulminant endocarditis caused by S. aureus on NORMAL valves. (damaged valves)

GAMMA-hemolytic (no hemolysis):

💡 Enterococcus (formerly Group D Strep) — gamma-hemolytic (no hemolysis). Grows in 6.5% NaCl and is bile esculin positiveEnterococcus can hydrolyze esculin in the presence of bile (40% bile). This produces a black precipitate on the agar. Group D strep (including Enterococcus) are bile esculin positive, but only Enterococcus grows in 6.5% NaCl. That's the final differentiator.. Important cause of UTIs, biliary infections, and VREVancomycin-Resistant Enterococcus. A major nosocomial pathogen. Treat with linezolid or daptomycin. VRE modified the D-Ala-D-Ala peptidoglycan target to D-Ala-D-Lac, so vancomycin can't bind..

An alpha-hemolytic organism is isolated. You run an optochin sensitivity test. It's RESISTANT. What is the organism?

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Sort Them — Drag Each Organism Home

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Drag each organism into the correct category. No peeking back up.

Round 1: Catalase — Staph or Strep?

Staph (Catalase +)

Strep (Catalase −)

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The Decision Tree — From Gram Stain to Organism

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This is the algorithm. You see gram-positive cocci. Walk through each branch. At each fork, you'll be quizzed before the path reveals.

Gram stain shows gram-positive cocci. You see them arranged in clusters. What test do you run first?

Catalase first. Always.

Clusters suggest Staph, but you confirm with catalase. Coagulase comes AFTER you've established it's Staph. Optochin is for differentiating alpha-hemolytic Strep — way too early.

Catalase is POSITIVE (bubbles). It's Staph. What test do you run next?

Coagulase. This is how you find S. aureus.

Bacitracin is for differentiating beta-hemolytic Strep (Group A vs B). Bile esculin is for Enterococcus. Coagulase splits the Staph family: positive = S. aureus, negative = CoNS.

Coagulase is NEGATIVE. It's CoNS. The patient is a 21-year-old woman with a UTI. What test differentiates S. epidermidis from S. saprophyticus?

Novobiocin. S. saprophyticus is resistant, S. epidermidis is sensitive.

In a young woman with a UTI + coagulase-negative staph, you're already thinking saprophyticus. But the lab confirmation is novobiocin resistance. Optochin differentiates pneumococcus from viridans (alpha strep, not staph). Bile solubility also goes with pneumococcus.

Now a different scenario: gram-positive cocci in CHAINS, catalase NEGATIVE. You plate it on blood agar and see complete clearing around the colonies (clear zone). What hemolysis pattern is this?

Beta. Complete clearing = complete lysis of red blood cells.

Beta = bloody destruction (clear zone). Alpha = almost (green zone, partial). Gamma = gone — no hemolysis at all.

Beta-hemolytic strep. What test differentiates Group A from Group B?

Bacitracin. Group A (S. pyogenes) is sensitive. Group B (S. agalactiae) is resistant.

Optochin = alpha-hemolytic strep (pneumo vs viridans). Novobiocin = coagulase-negative staph (epidermidis vs saprophyticus). Each test belongs to a specific branch of the tree. Don't cross the streams.

New scenario: alpha-hemolytic strep (green zone). What test differentiates S. pneumoniae from viridans group?

Optochin. Pneumococcus is sensitive. Viridans is resistant.

You can also use bile solubility (pneumococcus dissolves in bile, viridans doesn't). But optochin is the classic board answer. Remember: OPTochin = Pneumo is Sensitive.

The Full Algorithm (reference):

Gram-positive cocci

↓ Catalase test

Catalase +
STAPH (clusters)

Catalase −
STREP (chains)

STAPH branch
Coagulase test

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Coag +
S. aureus

Coag − (CoNS)
Novobiocin test

CoNS + Novobiocin

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Sensitive
S. epidermidis

Resistant
S. saprophyticus

STREP branch
Hemolysis pattern

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Beta
Bacitracin

Alpha
Optochin

Gamma
Bile esculin + NaCl

Bacitracin S
GAS (pyogenes)

Bacitracin R
GBS (agalactiae)

Optochin S
S. pneumoniae

Optochin R
Viridans

Bile esc +, NaCl +
Enterococcus

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The Cheat Sheet — All 8 Organisms

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Everything on one table. Scroll sideways on mobile.

Organism	Catalase	Key Test	Hallmark	Top Disease
S. aureus	+	Coagulase +	Golden pigment, protein A	Skin, endocarditis, osteo, MRSA
S. epidermidis	+	Novobiocin S	Biofilm on prosthetics	Prosthetic valve/joint infections
S. saprophyticus	+	Novobiocin R	UTI bug in young women	UTI (#2 after E. coli)
S. pyogenes (GAS)	−	Bacitracin S	Beta-hemolysis	Pharyngitis, rheumatic fever, NF
S. agalactiae (GBS)	−	Bacitracin R	Beta-hemolysis	Neonatal meningitis/sepsis
S. pneumoniae	−	Optochin S	Alpha, lancet diplococci	Meningitis, pneumonia (#1 both)
Viridans group	−	Optochin R	Alpha, dental flora	Subacute endocarditis (damaged valves)
Enterococcus	−	Bile esculin +, 6.5% NaCl	Gamma (no hemolysis)	UTIs, biliary, VRE

💡 Test-to-branch cheat: Coagulase = Staph. Bacitracin = Beta Strep. Optochin = Alpha Strep. Novobiocin = CoNS. Bile esculin + NaCl = Enterococcus. Each test lives on ONE branch. Don't cross them.

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Quiz — 4 Lab Results, 4 Organisms

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5 patients just showed up with infections. The micro lab sent results. Match the bug to the patient before rounds start.