Gastrointestinal

Acute diarrhea: infectious workup and management

Clinical Overview and When to Suspect Acute Infectious Diarrhea

— Persistent diarrhea: 14–29 days

— Chronic diarrhea: ≥30 days (different workup paradigm — think IBD, malabsorption, microscopic colitis)

— ~179 million cases/year in the US; most are viral and self-limited

— Norovirus is the leading cause of acute gastroenteritis in US adults across all care settings

— Bacterial pathogens (Salmonella, Campylobacter, Shigella, STEC, C. difficile) drive most ED visits and hospitalizations

— Fever ≥38.5°C, bloody or mucoid stools, severe abdominal pain

— Profuse watery diarrhea with hypovolemia

— Duration >7 days or worsening after 72 hours

— Age ≥70, immunocompromise, IBD, pregnancy

— Recent antibiotic, chemotherapy, or PPI exposure → think C. difficile

— Recent hospitalization, nursing home, or healthcare worker

— Outbreak setting (daycare, cruise ship, food service)

— Undercooked beef/leafy greens → STEC O157:H7

— Poultry, eggs, reptiles → Salmonella

— Unpasteurized dairy, puppies → Campylobacter, Yersinia

— Fried rice → Bacillus cereus (short incubation, emetic)

— Raw shellfish → Vibrio parahaemolyticus, norovirus

— Recent travel → ETEC, Shigella, Giardia, Entamoeba

— MSM → Shigella, Giardia, LGV-proctitis

Definition: ≥3 loose/watery stools per day (or stool volume >250 g/day) lasting <14 days

Epidemiology and burden

When to suspect a bacterial/invasive etiology — these patients warrant testing, not just supportive care:

Exposure-driven suspicion (Step 3 favorite)

Board pearl: The single most actionable distinction in acute diarrhea is inflammatory (invasive) vs non-inflammatory (secretory/watery) — it determines whether you test stool, give antibiotics, or just rehydrate. Fever + blood + tenesmus = inflammatory until proven otherwise; large-volume watery + vomiting in a healthy adult = supportive care only.

Presentation Patterns and Key History

— Large-volume, watery, non-bloody stools

— Periumbilical cramps, nausea, vomiting prominent

— Usually afebrile or low-grade temp

— Pathogens: norovirus, rotavirus, ETEC, Vibrio cholerae, preformed toxins (S. aureus, B. cereus)

— Small-volume, frequent stools with blood, mucus, tenesmus

— Fever, lower abdominal/LLQ pain

— Pathogens: Shigella, Salmonella, Campylobacter, STEC, EIEC, Entamoeba histolytica, C. difficile, Yersinia

— <6 hours: preformed toxin (S. aureus, B. cereus emetic) — vomiting dominant

— 8–16 hours: C. perfringens, B. cereus diarrheal type

— 16–72 hours: most bacteria (Salmonella, Shigella, Campylobacter, ETEC, Vibrio, norovirus)

— Days to weeks: Giardia, Cryptosporidium, Cyclospora, Entamoeba

— Stool character: volume, frequency, blood, mucus, floating/greasy (steatorrhea suggests Giardia)

— Associated symptoms: vomiting, fever, weight loss, arthralgia, rash

— Sick contacts, daycare exposure, institutional outbreak

— Food: undercooked meat, raw seafood, unpasteurized dairy, picnics, restaurants

— Travel within 6 weeks (region-specific pathogens)

— Water: well water, lakes/streams → Giardia, Cryptosporidium

— Antibiotics, chemotherapy, PPI, recent hospitalization → C. difficile

— Sexual practices (receptive anal) → proctitis pathogens

— Immune status: HIV, transplant, biologics — broaden differential

Non-inflammatory (small bowel, secretory) pattern

Inflammatory (colonic, invasive/dysenteric) pattern

Incubation timing is the highest-yield history element

Targeted history checklist

Key distinction: Vomiting predominant with onset <6 hours after a shared meal = preformed toxin (S. aureus, B. cereus emetic) — no stool studies, no antibiotics, just hydration and reassurance. Do not confuse with norovirus, which has a 12–48 h incubation and prominent diarrhea alongside vomiting.

Physical Exam Findings and Hemodynamic Assessment

— Mild dehydration (<5% loss): dry mucous membranes, thirst, normal vitals

— Moderate (5–9%): tachycardia, orthostatic drop ≥20 mmHg systolic or ≥10 diastolic, decreased skin turgor, oliguria, capillary refill 2–3 sec

— Severe (≥10%): hypotension, altered mental status, cool extremities, anuria, sunken eyes, capillary refill >3 sec → shock

— Diffuse tenderness without peritoneal signs → typical gastroenteritis

— RLQ tenderness mimicking appendicitis → Yersinia enterocolitica (mesenteric adenitis, terminal ileitis)

— LLQ tenderness, tenesmus → Shigella, EIEC, amebic colitis

— Severe pain out of proportion, abdominal distension, fever → consider toxic megacolon (C. difficile, severe Shigella, STEC) — get imaging, surgical consult

— Rebound/guarding → perforation, surgical abdomen — STOP antimotility agents

— Rose spots on trunk → typhoid (Salmonella Typhi)

— Reactive arthritis (Reiter): post-Campylobacter, Shigella, Salmonella, Yersinia (HLA-B27)

— Erythema nodosum: Yersinia, Campylobacter

— Guillain-Barré in 2–3 weeks post-Campylobacter

— Petechiae, pallor, oliguria 5–10 days into STEC illness → HUS

— Tachycardia disproportionate to fever → volume depletion

— Hypotension + bradycardia in elderly: consider sepsis, medication effects

— Fever >39°C with bloody diarrhea: invasive bacterial — culture and admit if unstable

Volume status — the single most important exam in acute diarrhea

Abdominal exam clues

Extra-intestinal findings

Vital sign pearls

CCS pearl: On a CCS case, the first three orders for any moderate-to-severe acute diarrhea are vital signs with orthostatics, IV access, and isotonic crystalloid bolus (NS or LR 500 mL–1 L). Then order labs and stool studies. Don't anchor on antibiotics before you've documented volume resuscitation and assessed perfusion.

Diagnostic Workup — Initial Labs and Stool Studies

— Healthy adult, <72 h, watery, no fever, no blood, no red flags → empiric oral rehydration, no labs

— Bloody or mucoid stools

— Fever ≥38.5°C

— Severe abdominal pain, signs of sepsis

— Hypovolemia requiring IV fluids

— Symptoms >7 days or persistent

— Immunocompromise, age ≥70, pregnancy, IBD

— Recent antibiotics or hospitalization (test for C. diff)

— Suspected outbreak (public health reporting)

— Multiplex PCR stool panel (now preferred where available) — detects Salmonella, Shigella, Campylobacter, STEC (including Shiga toxin 1/2), Yersinia, Vibrio, ETEC/EPEC, norovirus, rotavirus, Giardia, Cryptosporidium, Entamoeba in hours

— Stool culture if PCR unavailable; specify Shiga toxin testing for bloody diarrhea

— C. difficile testing (only if ≥3 unformed stools/24 h AND risk factors): NAAT + toxin EIA two-step algorithm preferred; do not test asymptomatic patients or formed stool

— Ova & parasites: only if >7 days, travel, daycare, immunocompromise, MSM, waterborne exposure

— Stool lactoferrin or fecal leukocytes: cheaper screen for inflammatory diarrhea; less used now

— CBC: leukocytosis, eosinophilia (parasites), schistocytes + thrombocytopenia → HUS

— BMP: AKI, hyponatremia, hypokalemia, metabolic acidosis from bicarb loss

— Lactate, blood cultures if febrile/septic-appearing

— LFTs if cholestatic features (consider hepatitis A from same food exposure)

Most acute diarrhea needs NO testing

Indications to test (IDSA 2017):

First-line stool diagnostics

Adjunctive blood work in moderate/severe illness

Board pearl: In suspected STEC (bloody diarrhea, recent ground beef), send stool for Shiga toxin AND culture for O157:H7, and avoid empiric antibiotics and antimotility drugs — both increase HUS risk. Check CBC, creatinine, and LDH/haptoglobin/peripheral smear at baseline and again at 5–7 days.

Diagnostic Workup — Advanced and Confirmatory Studies

— Repeat or extend stool panel; add O&P ×3 on separate days (Giardia shedding is intermittent)

— Giardia/Cryptosporidium antigen EIA — higher sensitivity than microscopy

— Stool elastase, fat — if malabsorption suspected (think chronic, not acute)

— Plain abdominal radiograph: if pain/distension — look for ileus, megacolon (transverse colon >6 cm), free air

— CT abdomen/pelvis with contrast: severe pain, peritonitis, suspected complications

— Pancolitis with mural thickening → C. difficile, severe infectious colitis

— Terminal ileitis → Yersinia, Crohn, TB

— Right-sided colitis → CMV in immunocompromised, neutropenic enterocolitis

— Sigmoidoscopy/colonoscopy if diagnostic uncertainty: distinguish IBD flare from infectious colitis, evaluate CMV in immunocompromised, pseudomembranes (C. diff)

— Biopsy for amebic colitis (flask-shaped ulcers, trophozoites with ingested RBCs), CMV inclusions

— Returned traveler: stool culture + O&P + Giardia/Cryptosporidium antigen; consider Entamoeba serology if liver abscess suspected

— Immunocompromised/HIV CD4 <200: broader panel including Cryptosporidium, microsporidia, Isospora/Cystoisospora, Cyclospora, CMV, MAC

— Suspected HUS: CBC with smear, LDH, haptoglobin, BUN/Cr, urinalysis; nephrology consult

— Post-antibiotic diarrhea negative for C. diff: consider Klebsiella oxytoca, functional, microscopic colitis

— Mandatory reporting in US: Salmonella, Shigella, STEC, Campylobacter, Vibrio cholerae, Giardia, Cryptosporidium, hepatitis A, and any suspected outbreak

When initial stool studies are negative but illness persists or worsens

Imaging

Endoscopy (rarely needed acutely)

Special situations

Public health reporting (Step 3 loves this)

Step 3 management: If a patient has bloody diarrhea and STEC is on the differential, order Shiga toxin testing reflexively, hold antibiotics and loperamide pending results, and arrange follow-up labs (CBC, creatinine) at days 3, 5, and 7 to catch evolving HUS before AKI and TMA become advanced.

Risk Stratification and First-Line Management Logic

— Outpatient + ORT alone: mild–moderate illness, tolerating PO, no red flags, normal vitals

— Outpatient + diagnostics: red-flag features but stable hemodynamics (fever, blood, prolonged duration)

— ED/observation: moderate dehydration not corrected with PO, vomiting preventing rehydration, electrolyte abnormalities

— Admit: severe dehydration/shock, sepsis, AKI, suspected HUS, toxic megacolon, age ≥70 with comorbidity, immunocompromise with high fever

— Oral rehydration solution (ORS) is first-line for mild-to-moderate dehydration in ALL ages (WHO/CDC)

— Glucose-sodium cotransport keeps absorption working even in secretory diarrhea

— Sports drinks and juices are inferior (too much sugar, too little sodium); ok for mild illness

— IV fluids when shock, ileus, intractable vomiting, or altered mental status

— Bolus isotonic crystalloid (NS or LR) 20 mL/kg, reassess; LR preferred in large-volume loss (less hyperchloremic acidosis)

— Replace potassium aggressively — diarrhea drives substantial K+ loss

— Early refeeding shortens illness; avoid prolonged NPO or "BRAT" alone

— Resume regular age-appropriate diet as tolerated; avoid lactose if symptoms suggest transient lactase deficiency

— Probiotics: modest benefit for antibiotic-associated diarrhea; not routinely recommended for infectious diarrhea

— Acceptable in mild, non-bloody, afebrile diarrhea in adults

— Contraindicated with bloody diarrhea, high fever, suspected STEC, C. difficile, severe colitis, children <2

Triage decision tree

Rehydration is the cornerstone

Diet

Antimotility agents (loperamide)

Board pearl: The default for an otherwise healthy adult with acute watery diarrhea is ORS + early refeeding + symptomatic care; no stool studies, no antibiotics. Reserve workup and pharmacology for the red-flag patient. Overtesting in mild self-limited illness is a common Step 3 wrong answer.

Pharmacotherapy — First-Line Antimicrobial Regimens

— Ciprofloxacin 500 mg PO BID × 3–5 days OR levofloxacin 500 mg daily

— Azithromycin 500 mg daily × 3 days preferred for travel to South/Southeast Asia (fluoroquinolone-resistant Campylobacter)

— Avoid empiric antibiotics if STEC is on the differential (bloody diarrhea + ground beef/leafy green exposure)

— Shigella: ciprofloxacin or azithromycin × 3 days (treat all — reduces transmission)

— Campylobacter: azithromycin × 3 days (most regions have FQ resistance)

— Salmonella, non-typhoidal: treat ONLY if severe, bacteremic, age <3 mo or >50, immunocompromise, prosthetic device, sickle cell — ciprofloxacin or ceftriaxone (otherwise antibiotics prolong carriage)

— Salmonella Typhi/Paratyphi: ceftriaxone or azithromycin

— Vibrio cholerae: doxycycline single dose 300 mg (azithromycin alternative); aggressive ORS

— ETEC (travelers'): azithromycin 1 g single dose or 500 mg ×3 days; rifaximin 200 mg TID ×3 d for non-dysenteric

— Giardia: tinidazole 2 g single dose or metronidazole 500 mg TID ×5–7 d (nitazoxanide alternative)

— Entamoeba histolytica: metronidazole 500–750 mg TID ×7–10 d followed by paromomycin or iodoquinol to eradicate luminal cysts

— Cryptosporidium: nitazoxanide (immunocompetent); restore immune function in HIV

— C. difficile (first episode, non-severe or severe): fidaxomicin 200 mg BID ×10 d (preferred per IDSA 2021) or vancomycin 125 mg PO QID ×10 d; metronidazole only if neither available

— Fulminant C. diff: vancomycin 500 mg PO/NG QID + IV metronidazole 500 mg q8h ± rectal vanc

General principle: Most acute diarrhea is viral or self-limited bacterial — empiric antibiotics are NOT routine. Use when benefit outweighs risk: severe illness, sepsis, immunocompromise, travelers' diarrhea, specific pathogens.

Empiric therapy when indicated (severe febrile invasive diarrhea, adult)

Pathogen-directed therapy

Step 3 management: A patient with bloody diarrhea after eating undercooked beef gets supportive care, stool Shiga toxin testing, and no antibiotics, no loperamide — both increase HUS risk in STEC. This is one of the most tested pharmacology traps in GI infectious disease.

Expanded Pharmacology — Adjuncts, Resistance, and Recurrence

— Loperamide: 4 mg load then 2 mg after each loose stool, max 16 mg/day; safe in mild non-inflammatory diarrhea; can combine with antibiotic in travelers' diarrhea for faster symptom relief

— Avoid in bloody/dysenteric illness, suspected STEC/C. diff, high fever, children <2

— Bismuth subsalicylate: 524 mg q30–60 min, max 8 doses/day; modest benefit; turns stool/tongue black; avoid in salicylate sensitivity, renal failure, children with viral illness (Reye)

— Crofelemer: approved for non-infectious HIV-related diarrhea

— Ondansetron 4–8 mg ODT — facilitates ORT, reduces IV need; QT caution

— Promethazine, metoclopramide — alternatives, more side effects

— Food/water precautions are first-line

— Bismuth subsalicylate 2 tabs QID — reduces incidence ~50%

— Prophylactic antibiotics not routine; rifaximin for high-risk travelers (IBD, immunocompromise) with short trips

— Vaccines: typhoid (oral Ty21a or IM Vi), cholera (Vaxchora) for high-risk travel

— First recurrence: fidaxomicin (preferred) or vancomycin tapered/pulsed regimen

— Second recurrence: vancomycin taper + pulse OR fidaxomicin OR fecal microbiota transplant (FMT)

— Bezlotoxumab (monoclonal anti-toxin B) — add to standard therapy in patients at high risk of recurrence (age ≥65, immunocompromise, prior CDI, severe CDI)

— Stop unnecessary PPIs and broad-spectrum antibiotics; this is a Step 3 stewardship point

— Increasing FQ resistance in Campylobacter, Shigella, Salmonella — azithromycin is often safer empirically in travelers from Asia

— ESBL-producing organisms in returning travelers (especially South Asia) — ceftriaxone may fail; use carbapenem if severe

Antimotility and antisecretory agents

Antiemetics

Travelers' diarrhea prevention

C. difficile recurrence management

Resistance considerations

CCS pearl: When managing C. difficile on CCS, the high-yield orders are discontinue offending antibiotic if possible, start fidaxomicin or oral vancomycin, contact isolation with soap-and-water hand hygiene (alcohol gel does NOT kill spores), and avoid antimotility agents. Recheck creatinine and WBC daily; rising WBC >15k or lactate >2.2 signals severe disease needing escalation.

Special Populations — Elderly and Renal/Hepatic Impairment

— Higher risk of severe dehydration, AKI, electrolyte abnormalities — baseline reduced thirst, lower total body water, polypharmacy

— Diuretics, ACEi/ARB, SGLT2 inhibitors, metformin, NSAIDs should be held during acute diarrhea ("sick day rules") to prevent AKI and lactic acidosis

— Higher mortality from C. difficile, Salmonella bacteremia, norovirus in nursing homes

— Lower threshold to admit, test, and treat empirically

— Bacteremia risk with non-typhoidal Salmonella much higher → treat with ceftriaxone or ciprofloxacin × 7–14 days even if not "severe"

— Adjust fluoroquinolones, TMP-SMX, nitazoxanide for CrCl

— Ciprofloxacin: 250–500 mg q12h if CrCl 30–50; q24h if <30

— Avoid magnesium-containing ORS in advanced CKD

— Hyperkalemia paradoxically common despite GI losses if AKI develops — monitor closely

— Bismuth subsalicylate contraindicated (salicylate accumulation, encephalopathy risk)

— Diarrhea precipitates hepatic encephalopathy via volume depletion and electrolyte shifts

— Metronidazole: reduce dose in severe hepatic dysfunction (Child-Pugh C); prolonged courses risk neurotoxicity

— Rifaximin commonly used in cirrhosis; minimal absorption, safe

— SBP must be excluded in cirrhotic with fever + diarrhea — diagnostic paracentesis

— Avoid loperamide in advanced cirrhosis with encephalopathy risk

— Hold metformin (lactic acidosis with AKI), SGLT2 inhibitors (DKA risk, volume depletion)

— Reduce insulin/sulfonylurea doses; monitor glucose closely

— Gastroparesis can mimic or coexist with infection

Elderly (≥65)

CKD and dialysis patients

Hepatic impairment/cirrhosis

Diabetic patients

Board pearl: "Sick day" instructions for any elderly patient with acute diarrhea: hold ACE/ARB, diuretics, SGLT2i, metformin, and NSAIDs; push oral fluids; return if unable to keep fluids down, oliguric, or symptoms persist >48 h. This medication-reconciliation step is a recurring Step 3 ambulatory question and a frequent root cause of preventable AKI admissions.

Special Populations — Pregnancy, Pediatrics, Immunocompromised

— Volume depletion can precipitate preterm labor and uteroplacental hypoperfusion — low threshold for IV fluids

— Listeria monocytogenes must be considered — febrile gastroenteritis in pregnancy → blood cultures, empiric ampicillin (not ceftriaxone, which doesn't cover Listeria)

— Avoid: ciprofloxacin (cartilage), TMP-SMX (1st trimester folate antagonism, 3rd trimester kernicterus), tetracyclines, metronidazole controversial in 1st trimester (use after if needed)

— Safe: azithromycin, ceftriaxone, ampicillin, nitazoxanide (limited data, use if clearly indicated)

— Hepatitis E severe in pregnancy (returning traveler with jaundice)

— ORS first-line; WHO low-osmolarity formulation

— Ondansetron single dose facilitates ORT and reduces hospitalization

— Avoid loperamide in <2 years; caution to 6 years

— Rotavirus vaccination (RV1, RV5) — most important prevention; live vaccine, complete by 8 months

— STEC and HUS overrepresented in young children — never give antibiotics or antimotility for bloody diarrhea in a child until STEC excluded

— Breastfeeding should continue throughout illness

— Broader pathogen list: Cryptosporidium, microsporidia, Cystoisospora, Cyclospora, CMV colitis, MAC, atypical Salmonella

— Lower threshold for multiplex PCR, blood cultures, and CMV workup

— HIV CD4 <100: cryptosporidiosis can be chronic and life-threatening — ART restoration is the definitive treatment

— Neutropenic enterocolitis (typhlitis): right-sided pain + fever + neutropenia → CT, broad-spectrum antibiotics, surgical consult

— Consider gonorrhea, chlamydia (including LGV), syphilis, HSV alongside enteric pathogens; rectal NAAT

Pregnancy

Pediatrics (recognize even though Step 3 family medicine)

Immunocompromised (HIV, transplant, chemo, biologics)

MSM and STI-related proctitis

Step 3 management: A pregnant patient at 28 weeks with fever, myalgia, and diarrhea after deli meats or soft cheese should be admitted, blood-cultured, and started on IV ampicillin for presumed listeriosis while awaiting cultures — even if symptoms seem mild, fetal risk (chorioamnionitis, fetal demise) is high.

Complications and Adverse Outcomes

— Hypovolemic shock, prerenal AKI, ATN if uncorrected

— Hypokalemia → arrhythmia, ileus, weakness

— Hyponatremia (free water replacement without sodium)

— Non-anion-gap metabolic acidosis from bicarbonate loss

— Hypomagnesemia, hypocalcemia in severe/protracted illness

— STEC O157:H7 most common; develops 5–10 days after diarrhea onset

— Triad: microangiopathic hemolytic anemia, thrombocytopenia, AKI

— Children and elderly highest risk

— Management: supportive — IV fluids, transfusion, dialysis as needed; no antibiotics, no antimotility, no platelet transfusion unless bleeding

— Eculizumab for atypical HUS, not typical STEC-HUS

— C. difficile, severe Shigella, amebic colitis, CMV

— Fever, tachycardia, distension, transverse colon >6 cm on imaging

— Surgical consult; emergent colectomy if perforation, refractory shock, or worsening despite medical therapy

— Non-typhoidal Salmonella: endovascular seeding (aortitis, mycotic aneurysm), osteomyelitis (sickle cell), septic arthritis

— Campylobacter: Guillain-Barré (Miller Fisher variant), reactive arthritis

— Yersinia: erythema nodosum, reactive arthritis, terminal ileitis mimicking appendicitis

— Reactive arthritis (HLA-B27): Shigella, Salmonella, Campylobacter, Yersinia — urethritis, conjunctivitis, arthritis (incomplete forms common)

— Post-infectious IBS (10–15%)

— Lactose intolerance (transient, weeks)

— IBD unmasking after enteric infection

— Hepatitis A from same shellfish/produce exposure — vaccinate close contacts within 14 days

— Public health investigation when ≥2 linked cases

Volume and electrolyte disorders

Hemolytic uremic syndrome (HUS)

Toxic megacolon and perforation

Bacteremia and metastatic infection

Post-infectious sequelae

Outbreak-related

Board pearl: Any patient with non-typhoidal Salmonella bacteremia age >50 must be evaluated for mycotic aortic aneurysm with CT angiography — a frequently missed diagnosis that presents weeks later with back pain, fever, and rupture. Treat bacteremia with prolonged IV ceftriaxone or ciprofloxacin and follow with surveillance imaging.

When to Escalate Care — ICU, Consults, Inpatient Triage

— Septic shock requiring vasopressors after adequate fluid resuscitation

— Severe metabolic acidosis (pH <7.2, bicarbonate <15)

— Acute kidney injury requiring dialysis

— Toxic megacolon, suspected perforation, peritonitis

— Fulminant C. difficile: hypotension, ileus, megacolon, lactate >2.2, WBC >25k or <5k

— HUS with anuria or neurologic involvement

— Altered mental status from severe dehydration or sepsis

— Inability to tolerate ORT (vomiting, altered mentation)

— Moderate–severe dehydration requiring ongoing IV fluids

— AKI not responsive to bolus

— Age ≥70 with comorbidities and febrile bacterial diarrhea

— Immunocompromise with high fever

— Suspected listeriosis in pregnancy

— Bacteremia (typhoid, invasive Salmonella, Vibrio vulnificus)

— Significant comorbidity decompensation (CHF, cirrhosis, ESRD)

— Infectious disease: persistent fever despite therapy, immunocompromise, unusual pathogens, suspected outbreak, suspected resistant organisms, returning international traveler with severe illness

— Gastroenterology: suspected IBD flare vs infection, persistent diarrhea >7–14 days, need for endoscopy, refractory C. difficile, FMT candidate

— Surgery: toxic megacolon, perforation, acute abdomen, neutropenic enterocolitis

— Nephrology: HUS, AKI requiring dialysis, severe electrolyte derangements

— Public health/infection control: reportable disease, outbreak, daycare/food handler involvement

— Ensure follow-up labs scheduled before discharge (especially STEC patients at risk for HUS — repeat CBC, Cr at 5–7 days)

— Medication reconciliation: restart held home meds with clear instructions

— Return precautions: bloody stools, decreased urine, confusion, persistent vomiting, fever >72 h

ICU admission criteria

Floor admission criteria

Consultation triggers

Transitions of care (Step 3 emphasis)

CCS pearl: On a CCS case of suspected fulminant C. difficile, the time-sensitive orders are oral vancomycin 500 mg q6h + IV metronidazole 500 mg q8h, surgery consult, abdominal CT, contact isolation, lactate, and serial abdominal exams. Delay in surgical consultation is a common clock-driven scoring penalty.

Key Differentials — Same-Category (Other Infectious) Causes

— Norovirus: abrupt vomiting + watery diarrhea, 12–48 h incubation, outbreaks (cruises, daycare, nursing homes); supportive care; PCR confirms in outbreaks

— Rotavirus: pediatric primarily; adults via children; vaccine-preventable

— Adenovirus, sapovirus, astrovirus: less common, similar presentation

— CMV colitis: immunocompromised, bloody diarrhea, colonoscopy with inclusion bodies

— Shigella: very low inoculum, dysentery, daycare/MSM; treat to reduce transmission

— Salmonella (non-typhoidal): poultry/eggs/reptiles; usually self-limited; treat only high-risk

— Salmonella Typhi: travel to South Asia; stepwise fever, relative bradycardia, rose spots, hepatosplenomegaly; ceftriaxone or azithromycin

— Campylobacter jejuni: poultry/puppies; bloody diarrhea + abdominal pain; azithromycin

— STEC (O157 and non-O157): ground beef, leafy greens, petting zoos; HUS risk; no antibiotics

— Yersinia enterocolitica: pork, unpasteurized milk; pseudoappendicitis with RLQ pain

— Vibrio parahaemolyticus: raw oysters/shellfish, warm coastal waters

— Vibrio cholerae: rice-water stools, endemic regions; aggressive ORS, doxycycline

— Listeria: deli meats, soft cheese, sprouts; pregnancy/elderly/immunocompromised

— S. aureus: rapid (1–6 h), preformed toxin, vomiting dominant

— B. cereus: fried rice (emetic, 1–6 h) or meats (diarrheal, 8–16 h)

— C. perfringens: reheated meats/gravy; 8–16 h; large outbreaks

— C. difficile: healthcare-associated diarrhea, antibiotic exposure

— ETEC: travelers' diarrhea; heat-labile/stable toxins

— Giardia: prolonged, foul-smelling, greasy stools, bloating; campers, daycare

— Cryptosporidium: pools, immunocompromised; chlorine-resistant

— Cyclospora: imported berries, basil; prolonged relapsing illness

— Entamoeba histolytica: travelers, MSM; bloody diarrhea + liver abscess (RUQ pain, fever)

Viral

Bacterial — invasive

Bacterial — toxin-mediated (non-invasive)

Parasitic

Key distinction: Giardia vs Cryptosporidium — both from water exposure, but Giardia is acid-fast negative with classic pear-shaped trophozoites and responds to tinidazole/metronidazole; Cryptosporidium is acid-fast positive, often self-limited in immunocompetent, treated with nitazoxanide, and devastating in HIV with low CD4.

Key Differentials — Other-Category (Non-Infectious) Causes

— Ulcerative colitis or Crohn flare can mimic infectious colitis

— ALWAYS rule out superimposed C. difficile in IBD flare (test stool reflexively)

— Chronicity, weight loss, extraintestinal manifestations, family history → IBD

— Calprotectin, colonoscopy with biopsy distinguish

— Older patients with vascular risk factors; sudden LLQ pain followed by bloody diarrhea

— Watershed areas (splenic flexure, rectosigmoid); CT shows thumbprinting/mural thickening

— Often resolves with bowel rest and supportive care; surgery if necrosis

— Metformin, magnesium-containing antacids, colchicine, mycophenolate, chemotherapy, immune checkpoint inhibitors (checkpoint inhibitor colitis — high-yield: hold drug, start corticosteroids, infliximab if refractory)

— Laxative abuse

— SSRIs, PPIs (microscopic colitis association)

— Chronic watery non-bloody diarrhea, normal colonoscopy appearance, biopsy diagnostic (lymphocytic or collagenous)

— Associated with NSAIDs, PPIs, SSRIs; women >50

— Budesonide first-line

— Hyperthyroidism: weight loss, tachycardia, hyperdefecation

— Diabetic enteropathy: autonomic neuropathy, nocturnal diarrhea

— Addison disease: diarrhea + hypotension + hyperpigmentation

— Carcinoid (flushing), VIPoma (massive secretory, WDHA), gastrinoma

— Celiac disease, pancreatic insufficiency, bile acid diarrhea (post-cholecystectomy), lactose intolerance

— IBS-D: chronic, no alarm features; diagnosis after exclusion

— Post-infectious IBS — common after Campylobacter, Salmonella

— GI bleed mimicking dysentery (melena vs bloody diarrhea)

— Diverticulitis with sympathetic diarrhea

— Appendicitis early phase

— Pelvic inflammatory disease

— C. perfringens enteritis necroticans

— Eosinophilic gastroenteritis

Inflammatory bowel disease

Ischemic colitis

Medication-induced

Microscopic colitis

Endocrine and metabolic

Malabsorption

Functional

Other

Board pearl: A 60-year-old on melanoma immunotherapy (pembrolizumab/ipilimumab) presenting with diarrhea is immune checkpoint inhibitor colitis until proven otherwise — hold the drug, rule out infection (especially C. diff), and start prednisone 1 mg/kg; escalate to infliximab or vedolizumab if no improvement in 3–5 days. This is one of the highest-yield emerging Step 3 scenarios.

Secondary Prevention, Discharge Plan, and Long-Term Management

— Hand hygiene with soap and water (especially for C. diff and norovirus — alcohol does not kill spores/norovirus)

— Food safety: cook ground beef to 160°F, poultry to 165°F, separate raw/cooked, refrigerate within 2 hours

— Avoid raw eggs, unpasteurized dairy, raw shellfish in high-risk individuals

— Safe water in travel: bottled/boiled, avoid ice; "boil it, cook it, peel it, or forget it"

— Food handlers, healthcare workers, daycare staff, daycare attendees: exclusion until asymptomatic ≥24–48 hours; some pathogens require negative stools (Shigella, STEC, typhoid, Salmonella in food handlers per local rules)

— Reportable diseases: ensure case report to health department filed

— Rotavirus in infants (RV1 or RV5 series)

— Typhoid (Ty21a oral or Vi polysaccharide IM) for travelers to endemic regions

— Cholera (Vaxchora) for adults traveling to active cholera areas

— Hepatitis A for travelers, MSM, IVDU, chronic liver disease, food handlers in some jurisdictions

— Norovirus vaccine in development; not yet available

— Limited evidence for prevention of antibiotic-associated diarrhea; not recommended routinely in adults; avoid in immunocompromised, central lines, critically ill (fungemia risk)

— Antibiotic stewardship — narrowest spectrum, shortest course

— Deprescribe unnecessary PPIs

— Consider bezlotoxumab in high-risk patients during retreatment

— Refer for FMT after second recurrence

— Pre-travel counseling, BSS prophylaxis option, standby antibiotic (azithromycin) + loperamide for self-treatment

Hygiene and food safety counseling at discharge

Return-to-work and exclusion rules (public health)

Vaccination

Probiotics

C. difficile recurrence prevention

Travelers' diarrhea prevention plan

Step 3 management: At discharge, hand the patient written return precautions (bloody stools, fever >72 h, oliguria, confusion, intolerance of PO), a follow-up appointment in 1–2 weeks, instructions to resume held home medications, and pathogen-specific exclusion rules if they are in a sensitive occupation. This bundle is the Step 3 ambulatory ideal.

Follow-Up, Monitoring Parameters, and Counseling

— Uncomplicated viral/bacterial diarrhea: 7–14 day primary care visit only if symptoms persist

— Bacterial pathogen with antibiotics: telephone or in-person check at 3–5 days to confirm resolution

— Elderly/comorbid patients: closer follow-up at 48–72 h with electrolyte/Cr recheck if home meds resumed

— Weekly CBC, BUN, creatinine, urinalysis for 2–3 weeks to detect HUS

— Educate patient/family on warning signs: pallor, decreased urine, bruising, lethargy

— Do NOT perform test-of-cure stool testing — NAAT remains positive for weeks in asymptomatic patients

— Monitor for recurrence (15–25% risk after first episode)

— Resume normal diet; probiotics not required

— Reassess with extended stool studies (Giardia, Cryptosporidium, Cyclospora, microsporidia)

— Consider post-infectious lactose intolerance — empiric lactose-free trial

— Evaluate for new IBD diagnosis if alarm features (weight loss, anemia, persistent blood)

— Bile acid diarrhea after Campylobacter or post-cholecystectomy — empiric cholestyramine trial

— Reassurance for self-limited illness; expected duration

— Adequate fluid intake instructions; signs of dehydration to monitor

— Diet: resume regular diet early; temporary lactose avoidance acceptable

— Sexual health counseling if STI-related proctitis identified

— Travel medicine consult for repeat travelers

— Health department may contact for outbreak investigation — patient should cooperate

— Notify daycare/employer per local exclusion rules

— Avoidance of unnecessary antibiotics is a stewardship quality measure

— Appropriate hydration education and reduction in unnecessary ED visits are tracked in value-based primary care

Routine outpatient follow-up

STEC/post-bloody diarrhea surveillance

C. difficile post-treatment

Persistent diarrhea (14–29 days)

Counseling and education

Public health follow-up

Quality measures and ambulatory metrics

Board pearl: Never order test-of-cure stool for C. difficile — positive NAAT in an asymptomatic patient after treatment reflects colonization, not failure. Retreatment based on a "positive cure test" is a common Step 3 wrong answer that perpetuates antibiotic exposure and recurrence.

Ethical, Legal, and Patient Safety Considerations

— Reportable enteric pathogens vary by state but commonly include: Salmonella, Shigella, STEC, Campylobacter, Vibrio, Yersinia, Listeria, hepatitis A, typhoid, cholera, Giardia, Cryptosporidium, Cyclospora

— Suspected outbreaks (≥2 linked cases) must be reported regardless of confirmed pathogen

— Reporting is a clinician duty that supersedes patient request for confidentiality — public welfare exception to confidentiality

— Food handlers, healthcare workers, daycare staff/attendees must be excluded per local rules; some require documented negative stool cultures (e.g., Shigella, STEC O157, typhoid)

— Clinician should document exclusion advice and provide return-to-work clearance

— Discuss with patients why antibiotics may worsen STEC outcomes or cause C. difficile — set expectations and prevent "antibiotic pressure" complaints

— Document shared decision-making when symptomatic therapy alone is chosen

— High-risk handoff: ED discharge of patient with bloody diarrhea pending Shiga toxin result — explicit safety net (callback if positive, scheduled labs, written return precautions)

— Closed-loop communication with primary care on pending test results is a Joint Commission–emphasized safety priority

— FMT for recurrent C. difficile requires informed consent including donor screening risks (transmission of multidrug-resistant organisms has occurred); document discussion

— Bezlotoxumab in elderly with heart failure carries CHF exacerbation risk — document risk-benefit

— Nursing home outbreaks: facility obligation to report, isolate, and cohort; clinician advocacy may be needed

— Pediatric STEC/HUS cases mandate child welfare evaluation only if neglect suspected (rare); typically a public health investigation only

— Listeriosis carries significant fetal risk; pregnant patients deserve clear counseling on dietary avoidance (deli meats, soft cheese, sprouts, unpasteurized products)

— Underserved patients may lack access to safe water, refrigeration, or sick leave — assess and connect with social services

Mandatory public health reporting (US)

Occupational exclusion

Antibiotic stewardship and informed decision-making

Transitions of care

Informed consent edge case

Vulnerable populations

Pregnancy considerations

Equity and access

Step 3 management: A food handler with confirmed Shigella must be excluded from work until two consecutive negative stool cultures (per most state rules), and the case must be reported to the local health department even without patient consent — this is a tested intersection of clinical care, occupational health, and public health law.

High-Yield Associations and Rapid-Fire Clinical Facts

— <6 h vomiting after potato salad/mayonnaise → S. aureus

— 1–6 h vomiting after fried rice → B. cereus emetic

— 8–16 h after church potluck/reheated gravy → C. perfringens

— 24–72 h watery diarrhea in traveler → ETEC

— 5–10 days post-bloody diarrhea → HUS (STEC)

— Undercooked ground beef, leafy greens, petting zoos → STEC O157

— Poultry, eggs, reptiles → Salmonella

— Puppies, unpasteurized milk → Campylobacter

— Pork chitterlings → Yersinia

— Raw oysters → Vibrio parahaemolyticus, V. vulnificus (cirrhotics — sepsis with bullae)

— Deli meats, soft cheese, sprouts → Listeria

— Imported raspberries, basil → Cyclospora

— Hiking/well water → Giardia

— Recreational water, swimming pools → Cryptosporidium

— Pseudoappendicitis (RLQ pain) → Yersinia

— Reactive arthritis (HLA-B27) → Shigella, Salmonella, Campylobacter, Yersinia

— Guillain-Barré → Campylobacter

— Erythema nodosum → Yersinia

— HUS → STEC (Shiga toxin)

— Liver abscess → Entamoeba histolytica

— Mycotic aortic aneurysm → non-typhoidal Salmonella, especially >50

— Osteomyelitis in sickle cell → Salmonella

— Sepsis with bullae in cirrhotic → Vibrio vulnificus

— Bloody diarrhea → culture + Shiga toxin

— >7 days/travel/MSM/immunocompromised → add O&P, Giardia/Crypto antigen

— Recent antibiotic/hospital → C. difficile NAAT + toxin EIA

— Don't treat non-typhoidal Salmonella in healthy adults (prolongs carriage)

— Don't give antibiotics or loperamide for STEC (HUS risk)

— Don't use alcohol hand gel for C. diff (use soap and water)

— Don't use TMP-SMX or fluoroquinolones in pregnancy

— Don't test for cure in C. difficile

— Rotavirus (infants), typhoid (travelers), cholera (high-risk travelers), hepatitis A (travelers, MSM, IVDU, CLD)

Incubation buzzwords

Food/exposure associations

Syndrome associations

Stool study triggers

Treatment "don'ts"

Vaccines worth knowing

Board pearl: "Five days after a hamburger, now pale and oliguric" — this is STEC-HUS until proven otherwise; the test isn't more antibiotics, it's CBC with smear, BUN/Cr, and supportive care. Pattern recognition on these vignettes saves time on test day.

Board Question Stem Patterns

— Multiple people sick within 4 hours of eating potato salad with vomiting — answer is S. aureus preformed toxin; management is oral hydration only, no antibiotics, no stool studies

— 6-year-old with bloody diarrhea 3 days after a cookout — answer pathogen is STEC O157:H7; correct next step is stool Shiga toxin testing + supportive care, NOT ciprofloxacin and NOT loperamide; surveillance CBC and creatinine

— Elderly inpatient on clindamycin develops watery diarrhea — answer is C. difficile; first-line treatment is fidaxomicin or oral vancomycin; metronidazole only if alternatives unavailable; soap-and-water hand hygiene; contact precautions

— Stepwise fever, rose spots, relative bradycardia, hepatosplenomegaly — answer is typhoid (Salmonella Typhi); treat with ceftriaxone or azithromycin (FQ resistance common in South Asia)

— Two weeks of foul-smelling diarrhea, bloating, weight loss after hiking — Giardia; stool antigen or PCR; treat with tinidazole single dose or metronidazole

— Consider Shigella, Entamoeba, LGV (Chlamydia), gonorrhea, HSV proctitis — broader STI panel including rectal NAAT

— Listeria → IV ampicillin; never ceftriaxone (no Listeria coverage); blood cultures mandatory

— Immune checkpoint inhibitor colitis → rule out infection, hold drug, prednisone 1 mg/kg, infliximab if refractory

— Salmonella osteomyelitis; ceftriaxone/ciprofloxacin

— Image abdominal aorta for mycotic aneurysm

— Yersinia enterocolitica; supportive care unless severe/immunocompromised

— Vibrio vulnificus; doxycycline + ceftriaxone, surgical debridement

Stem 1 — Watery diarrhea after potluck

Stem 2 — Bloody diarrhea after barbecue

Stem 3 — Hospitalized patient on antibiotics with new diarrhea

Stem 4 — Returning traveler from India

Stem 5 — Camper with prolonged greasy stools

Stem 6 — MSM with painful bloody bowel movements

Stem 7 — Pregnant patient with deli-meat exposure and fever

Stem 8 — Cancer patient on immunotherapy with diarrhea

Stem 9 — Sickle cell patient with osteomyelitis after diarrhea

Stem 10 — Elderly man with non-typhoidal Salmonella bacteremia

Stem 11 — Pseudoappendicitis with RLQ pain after pork

Stem 12 — Cirrhotic with sepsis and bullae after raw oysters

Step 3 management: When the stem gives you exposure + incubation + stool character, the diagnosis is usually pinned in one sentence. Then the question pivots — almost always — to "what is the BEST next step?" which is overwhelmingly oral rehydration, targeted stool testing, or avoidance of antibiotics, NOT empiric therapy. Default to less is more.

One-Line Recap

Acute infectious diarrhea is overwhelmingly self-limited and managed with oral rehydration; targeted stool testing and selective antibiotics are reserved for patients with red flags (bloody/dysenteric stools, high fever, severe dehydration, immunocompromise, age extremes, prolonged duration, healthcare/antibiotic exposure, or pregnancy), with key traps being antibiotics in STEC, alcohol gel in C. difficile, and treating non-typhoidal Salmonella in healthy adults.

Workup gate: No testing in healthy adult with <72 h watery non-bloody diarrhea; test stool (multiplex PCR or culture + Shiga toxin, plus C. diff if antibiotic-exposed, plus O&P if travel/>7 days) when red flags exist

Rehydration is therapy: ORS first-line at all ages and severities; IV crystalloid only when shock, intractable vomiting, or altered mental status — replace potassium aggressively

Antibiotic rules of thumb: Empiric ciprofloxacin or azithromycin only for severe febrile invasive diarrhea or travelers' diarrhea; never for suspected STEC; treat Shigella, severe Campylobacter, typhoid, cholera, Giardia, Entamoeba (with luminal agent), Listeria in pregnancy, and high-risk non-typhoidal Salmonella; first-line C. difficile is fidaxomicin or oral vancomycin, not metronidazole

Safety/system pearls: Report Salmonella, Shigella, STEC, Campylobacter, Listeria, Vibrio, hep A, and outbreaks; exclude food handlers/HCWs/daycare per local rules; surveil for HUS at days 5–7 after bloody diarrhea; deprescribe held home meds with sick-day rules in elderly; never order C. diff test-of-cure

Board pearl: When in doubt on a Step 3 vignette, the correct answer is usually rehydrate, test selectively, withhold antibiotics, and follow up — not the flashy empiric prescription.