LO 1

ON EXAM — clinical definition of diarrhea, viral vs bacterial vs protozoal buckets, Rotavirus/Norovirus triggers, invasive vs toxigenic bacterial framework, Campylobacter/Salmonella/Shigella/Yersinia/Listeria classic associations

Clinical definition of diarrhea

Frequency threshold

≥3 stools/day

Volume threshold

>200 g/day (Western diet)

Form description

Takes the shape of its container (watery/unformed)

Acute ≤ ______

2 weeks

Three pathogen buckets

Category	Representative Pathogens	Feature
Viruses	Rotavirus, Norovirus, Adenovirus, Astrovirus, Calicivirus	Most common overall cause of gastroenteritis
Bacteria	Campylobacter, Salmonella, Shigella, Yersinia, E. coli, Vibrio, Listeria, C. difficile; preformed-toxin: S. aureus, B. cereus, C. perfringens, C. botulinum	More likely in severe or bloody diarrhea
Protozoa/Parasites	Entamoeba, Giardia, Cryptosporidium, Cyclospora, Isospora, Microsporidia	Less common; chronic or travel-related

Viral diarrhea

Feature	Rotavirus	Norovirus
Classic population	Unvaccinated infants/young children	Adults of all ages
Classic setting	Daycare, winter, developing countries	Cruise ships, schools, nursing homes — outbreaks
Mechanism	NSP4 enterotoxin + villous blunting → watery osmotic/secretory diarrhea	Mucosal injury → vomiting-predominant, self-limited watery diarrhea
Vaccine?	Yes (live oral RotaTeq/Rotarix)	No

Invasive vs. toxigenic bacteria

Bug	Category	Signature
Campylobacter jejuni	Invasive	Curved GNR, undercooked poultry; GBS + reactive arthritis
Salmonella (non-typhoidal)	Invasive	Poultry, eggs, reptiles; bloody diarrhea, fever
Salmonella Typhi	Invasive (systemic)	Rose spots, stepwise fever, hepatosplenomegaly, gallbladder carrier
Shigella	Invasive	Low inoculum (~10 orgs); bloody mucoid; HUS via Shiga toxin
Yersinia enterocolitica	Invasive	Pseudoappendicitis (RLQ pain, mesenteric adenitis)
Listeria monocytogenes	Invasive	Soft cheeses/deli meats; meningitis in neonates, pregnant, elderly
Vibrio cholerae	Toxigenic (non-invasive)	Rice-water stools; cholera toxin ↑ cAMP

Campylobacter deep dive

Classic exposure

Undercooked poultry, unpasteurized milk, puppies

Morphology

Curved/comma ("seagull-shaped") gram-negative rod; motile; grows at 42 °C

Autoimmune complication 1

Guillain-Barré syndrome (molecular mimicry w/ gangliosides)

Complication 2

Reactive arthritis (HLA-B27)

Salmonella typhoidal vs non-typhoidal

Feature	Non-typhoidal	Typhoidal
Reservoir	Animal (poultry, eggs, reptiles)	Humans only
Classic exposure	Undercooked eggs/chicken, turtles	Travel to endemic (S. Asia), contaminated water
Key features	Gastroenteritis ± bloody; bacteremia in sickle cell/immunocompromised → osteomyelitis	Stepwise fever, rose spots, relative bradycardia, hepatosplenomegaly
Chronic carrier site	Rare	Gallbladder
Antibiotics?	Usually NOT (prolongs carriage); give if severe/immunocompromised	Yes — ceftriaxone or fluoroquinolone

Shigella

Infectious dose

Very low (~10–100 organisms)

Classic setting

Daycare/toddlers; febrile seizures can occur

Toxin

Shiga toxin (inhibits 60S ribosome)

Complication

Reactive arthritis (Reiter: can't see/pee/climb a tree); HUS (rare)

LO 1

ON EXAM — five E. coli pathotypes and their toxins/populations; Vibrio cholerae vs parahaemolyticus vs vulnificus; preformed-toxin bugs and their classic exposures/onsets

Pathogenic E. coli — 5 pathotypes

Pathotype	Full name	Population/Setting	Toxin/Mechanism	Stool
ETEC	Enterotoxigenic	Traveler's diarrhea (#1)	LT (↑ cAMP), ST (↑ cGMP)	Watery, non-inflammatory
EPEC	Enteropathogenic	Infants in developing countries	Pili adhere; effaces microvilli (no toxin)	Watery (pediatric)
EIEC	Enteroinvasive	Shigella-like	Invades mucosa (no toxin)	Bloody/dysenteric
EHEC (O157:H7)	Enterohemorrhagic	Undercooked beef, unpasteurized dairy, petting zoos	Shiga-like toxin (Stx)	Bloody → HUS
EAEC	Enteroaggregative	Chronic/persistent diarrhea in travelers + HIV	"Stacked-brick" adherence; plasmid toxins	Watery, can be prolonged

EHEC — HUS

HUS triad

Microangiopathic hemolytic anemia + thrombocytopenia + acute kidney injury

Toxin

Shiga-like toxin (Stx1/Stx2) — inhibits 60S ribosome on endothelial cells

Why avoid antibiotics

Antibiotic-induced bacterial lysis releases more Shiga toxin → ↑ HUS risk; also avoid anti-motility agents

Classic food

Undercooked ground beef; unpasteurized milk/juice; spinach

Vibrio species

Species	Exposure	Clinical
V. cholerae	Contaminated water; endemic regions	Rice-water diarrhea, massive volume loss, shock
V. parahaemolyticus	Raw/undercooked shellfish	Self-limited watery diarrhea, cramps
V. vulnificus	Raw oysters; wound contact with salt water	Sepsis, necrotizing fasciitis — especially in cirrhosis/hemochromatosis

Cholera toxin mechanism

Enzymatic activity

ADP-ribosylates Gsα (permanently activates it)

Target

Gαs of adenylate cyclase

Net effect

↑ cAMP → ↑ Cl⁻ + water secretion via CFTR → watery diarrhea

Preformed-toxin food poisoning

Bug	Classic food	Onset	Clinical
S. aureus	Mayo, cream pastries, potato salad	2–6 hours	Profuse vomiting; heat-stable enterotoxin
B. cereus (emetic)	Reheated fried rice	1–6 hours	Vomiting predominant (cereulide toxin)
B. cereus (diarrheal)	Meat, dairy, vegetables	8–16 hours	Watery diarrhea, cramps
C. perfringens	Reheated meats, gravy	8–16 hours	Watery diarrhea, cramps; self-limited
C. botulinum	Home-canned foods, honey (infants)	12–36 hours	Descending flaccid paralysis, bulbar palsies, dry mucous membranes

S. aureus speed

Why so fast

Toxin is preformed in the food — no replication needed in gut

Heat stability

Heat-STABLE — reheating does NOT inactivate

🪤 TRAP: "Preformed toxin" ≠ infection — the toxin is already in the food.

LO 2

ON EXAM — secretory vs invasive vs osmotic; cholera vs ETEC vs viral; dysentery (Shigella, EHEC, Campylobacter, Entamoeba, invasive Salmonella)

Secretory vs invasive vs osmotic

Type	Mechanism	Stool WBCs/blood	Prototype
Secretory	Toxin → ↑ fluid/electrolyte secretion; lumen remains open	Absent	Cholera, ETEC
Invasive	Mucosal invasion + inflammation	Present (fecal WBCs, blood)	Shigella, invasive Salmonella, Campylobacter, EIEC
Osmotic	Unabsorbed solute draws water into lumen	Absent	Rotavirus (partial), lactose intolerance, some protozoa

Cholera

Stool description

Rice-water (colorless, odorless, flecks of mucus)

Main problem

Massive isotonic volume loss → hypovolemic shock

Treatment

Aggressive fluid/electrolyte replacement (ORS or IV); doxycycline adjunct

Why ORS works

SGLT1 (Na-glucose cotransporter) still functions — drives absorption despite secretory losses

ETEC toxins

Two toxins

Heat-labile (LT) + heat-stable (ST)

LT mechanism

↑ cAMP (like cholera toxin — ADP-ribosylates Gsα)

ST mechanism

↑ cGMP (activates guanylate cyclase)

Viral watery diarrhea

Cruise ship outbreak, adults

Norovirus

Daycare, unvaccinated infant, winter

Rotavirus

Dysentery — clinical clues

Clue	Pathogen
Bloody diarrhea + HUS after undercooked beef	EHEC (O157:H7)
Bloody mucoid diarrhea + febrile seizures in toddler, low inoculum	Shigella
Bloody diarrhea after chicken, then ascending paralysis	Campylobacter jejuni → Guillain-Barré
Dysentery + flask-shaped ulcers + liver abscess	Entamoeba histolytica
RLQ pain mimicking appendicitis	Yersinia enterocolitica (pseudoappendicitis)

Entamoeba vs EHEC

Entamoeba unique

Liver abscess (RUQ pain, anchovy-paste contents, right lobe)

EHEC unique

HUS (MAHA + thrombocytopenia + AKI)

🪤 TRAP: Avoid anti-motility in bloody/febrile diarrhea; avoid antibiotics in suspected EHEC (↑ HUS).

LO 2

ON EXAM — traveler's (ETEC #1), C. difficile risk factors, toxins A/B, diagnosis, treatment, fulminant features

Traveler's diarrhea frequency

#1 cause

ETEC (30–60%)

#2 varies

Campylobacter, Salmonella, Shigella (region-dependent)

Viral

Norovirus (also on cruises)

Protozoal (prolonged)

Giardia, Cryptosporidium, Entamoeba

Traveler's — prevention + treatment

Primary prevention

"Boil it, cook it, peel it, or forget it"; bottled water; hand hygiene

Chemoprophylaxis

Bismuth subsalicylate; rifaximin (select cases — NOT for everyone)

First-line treatment

Azithromycin or ciprofloxacin (SE Asia → azithromycin due to FQ resistance); rifaximin for non-invasive

Symptom control

Loperamide — AVOID if bloody diarrhea or fever

C. difficile risk factors

Antibiotic #1

Fluoroquinolones

Antibiotic #2

Broad-spectrum β-lactams (piperacillin-tazobactam, carbapenems)

Antibiotic #3

Cephalosporins (3rd/4th gen)

Antibiotic #4

Clindamycin

Non-antibiotic

Long-term PPI use

Patient risk

Elderly, hospitalized, immunocompromised, IBD

C. difficile toxins

Toxin A (enterotoxin)

Binds intestinal brush border → fluid secretion + inflammation

Toxin B (cytotoxin)

Disrupts actin cytoskeleton → cell death and mucosal injury

Endoscopic finding

Pseudomembranous colitis (yellow plaques on colonic mucosa)

C. difficile diagnosis

Sensitive test

Stool PCR for toxin B gene (tcdB) or GDH antigen

Confirmatory

Stool toxin EIA (or cytotoxin cell assay)

Test only symptomatic because

Asymptomatic colonization is common; testing asymptomatic patients overtreats

C. difficile treatment

Scenario	Treatment
First episode, non-severe	Oral vancomycin OR oral fidaxomicin × 10 d
Severe / fulminant	Oral vancomycin (high-dose) + IV metronidazole
Recurrent (≥2nd)	Fidaxomicin, pulsed-tapered vancomycin, or fecal microbiota transplant (FMT); bezlotoxumab adjunct
Fulminant w/ ileus	Vancomycin enemas + IV metronidazole; surgery (colectomy) if failing

⚠️ Fulminant C. diff = hypotension/shock, ileus, toxic megacolon, perforation.

LO 3

ON EXAM — normal flora, empiric coverage; H. pylori Dx/Tx; pyogenic vs amebic liver abscess; SBP vs secondary vs CAPD peritonitis

Normal flora

Mouth pathogen 1

Viridans streptococci (S. mitis, S. sanguinis)

Mouth anaerobes

Peptostreptococcus, Prevotella, Fusobacterium, Actinomyces

Gut aerobe

E. coli (+ Klebsiella, Enterobacter, Enterococcus)

Gut anaerobe

Bacteroides fragilis

Empiric coverage for intraabdominal infection

Aerobic GNR coverage

E. coli, Klebsiella, Enterobacter

Anaerobic coverage

Bacteroides, Clostridium

Single-agent regimen

Piperacillin-tazobactam, or a carbapenem (meropenem/ertapenem)

Combo regimen

Ceftriaxone (or cipro) + metronidazole

H. pylori associations

Ulcer location

~90% duodenal, ~70% gastric

Malignancy 1

Gastric adenocarcinoma (intestinal type)

Malignancy 2

MALT lymphoma (can regress with eradication)

Acid-survival enzyme

Urease (urea → NH₃ + CO₂)

H. pylori diagnosis + treatment

Test/Regimen	Details
Urea breath test	Radiolabeled urea ingested → ¹³CO₂ in breath; non-invasive; avoid PPIs/antibiotics before testing
Stool antigen	Detects H. pylori antigen; good for screening and eradication follow-up
CLO test	Endoscopic biopsy + urea substrate → color change with urease activity
Triple therapy	PPI + clarithromycin + amoxicillin × 14 d
Quadruple therapy	PPI + bismuth + metronidazole + tetracycline × 10–14 d
Eradication confirmation	≥4 weeks after finishing antibiotics (urea breath test or stool antigen)

Pyogenic vs amebic liver abscess

Feature	Pyogenic	Amebic
Source	Biliary (ascending cholangitis), portal (diverticulitis/appy), hematogenous	Entamoeba histolytica from colon via portal circulation
Organisms	E. coli, Klebsiella, Streptococcus, anaerobes (often polymicrobial)	E. histolytica (single trophozoite)
Lobe	Right lobe most common	Right lobe (~80%)
Contents	Pus (creamy yellow)	"Anchovy paste" (necrotic, brown-red)
Treatment	Drainage + broad-spectrum antibiotics (e.g., ceftriaxone + metronidazole)	Metronidazole + luminal agent (paromomycin); drainage usually unnecessary

Peritonitis — three classifications

Type	Organism(s)	Diagnostic cutoff	Treatment
Primary (SBP)	Monomicrobial — E. coli (#1), Klebsiella, S. pneumoniae	Ascitic PMN ≥250/μL	Ceftriaxone × 5–7 d; albumin if Cr/bili elevated; long-term cipro prophylaxis
Secondary	Polymicrobial gut flora (E. coli, Bacteroides, Enterococcus)	Evidence of perforation or source; very high WBC, polymicrobial tap	Surgical source control + broad-spectrum antibiotics (pip-tazo or carbapenem)
CAPD	Skin flora — S. epidermidis (coagulase-negative staph), S. aureus	Cloudy dialysate, WBC >100/μL with >50% PMN	Intraperitoneal antibiotics (vancomycin + ceftazidime or gentamicin)

SBP specifics

PMN cutoff

≥250 cells/μL

Most common organism

E. coli

First-line antibiotic

Ceftriaxone (or cefotaxime) IV × 5–7 d

Secondary prophylaxis

Daily ciprofloxacin (or TMP-SMX) — lifelong after first SBP

🪤 TRAP: SBP is monomicrobial. Polymicrobial or very high PMN → think secondary peritonitis — needs surgery.

LOs 1–3

Q1: Traveler's diarrhea pathogen

A 28-year-old medical student returns from a 2-week trip to Mexico with 3 days of profuse watery diarrhea, abdominal cramps, and no blood. Stool studies show a non-inflammatory profile. Which pathogen is most likely?

A) EHEC (O157:H7)
B) Shigella
C) ETEC
D) Campylobacter jejuni
E) Norovirus

Correct Answer: C

ETEC is the #1 cause of traveler's diarrhea — watery, secretory, non-inflammatory (LT toxin ↑ cAMP; ST toxin ↑ cGMP). EHEC and Shigella cause dysentery. Campylobacter is possible but less common. Norovirus is plausible but less likely in this classic traveler presentation.

Q2: HUS after undercooked beef

A 5-year-old develops bloody diarrhea 4 days after a barbecue. Five days later he is pale, lethargic, with petechiae, oliguria, and Cr 2.9. Smear shows schistocytes. Which organism and toxin?

A) Shigella + Shiga toxin
B) EHEC + Shiga-like toxin (Stx)
C) ETEC + heat-labile toxin
D) Salmonella + LPS
E) Campylobacter + cytolethal distending toxin

Correct Answer: B

EHEC O157:H7 + Shiga-like toxin → HUS. Undercooked beef classic. Avoid antibiotics and anti-motility agents.

Q3: Preformed toxin — fast onset

Six people eat at a picnic; 3 hours later all develop vomiting and cramps. Recover in 24 h.

A) Salmonella
B) Campylobacter
C) S. aureus
D) EHEC
E) C. difficile

Correct Answer: C

S. aureus preformed enterotoxin → 2–6 h onset, vomiting predominant.

Q4: Invasive vs. toxigenic

34 M with bloody diarrhea, fever, leukocytosis after undercooked chicken. Stool WBCs +; curved gram-negative rods at 42 °C.

A) ETEC — toxigenic
B) Campylobacter jejuni — invasive
C) Vibrio cholerae — toxigenic
D) Listeria — invasive
E) Norovirus — viral

Correct Answer: B

Campylobacter jejuni (curved GNR at 42 °C). Post-infectious: GBS + reactive arthritis.

Q5: C. difficile first-line

67 M inpatient on ceftriaxone → 10 watery stools/day; toxin PCR + EIA positive; afebrile, WBC 14 k.

A) IV metronidazole alone
B) Oral vancomycin OR oral fidaxomicin
C) Oral ciprofloxacin
D) Loperamide
E) IV cefepime

Correct Answer: B

First-line is oral vancomycin OR fidaxomicin; metronidazole no longer first-line. Stop inciting antibiotic; never use loperamide.

Q6: SBP

58 M with cirrhosis/ascites, fever, abdominal pain. Paracentesis: PMN 320/μL, gram-negative rods on Gram stain.

A) Secondary peritonitis — polymicrobial
B) SBP — E. coli
C) CAPD peritonitis — S. epidermidis
D) TB peritonitis
E) Pancreatitis

Correct Answer: B

SBP: PMN ≥250; E. coli most common. Ceftriaxone × 5–7 d; long-term prophylaxis.

Q7: Amebic liver abscess

33 M from Mexico with bloody diarrhea, RUQ pain, fever; US shows single right-lobe lesion; E. histolytica serology +.

A) Percutaneous drainage alone
B) Metronidazole, then paromomycin
C) Ceftriaxone + metronidazole
D) Surgical resection
E) Oral vancomycin

Correct Answer: B

Metronidazole (tissue), then luminal agent (paromomycin) to eliminate cysts. Drainage usually unnecessary.

Q8: H. pylori triple therapy

Duodenal ulcer + positive urea breath test. Standard first-line?

A) Amox + metronidazole + bismuth (no PPI)
B) PPI + clarithromycin + amoxicillin
C) PPI alone × 8 wk
D) PPI + tetracycline alone
E) H2 blocker + clarithromycin alone

Correct Answer: B

Classic triple therapy: PPI + clarithromycin + amoxicillin × 14 d. Quadruple (PPI + bismuth + metro + tetracycline) for high clarithromycin resistance.

GI Infections — Answer Key