Between a Bug and a Flare: Sorting Acute Bloody Diarrhea in the First 48 Hours

Why this matters (and why it is hard)

Blood in stool with acute diarrhea straddles two high-stakes pathways: infectious enterocolitis (where early pathogen detection steers isolation and antibiotics) and inflammatory bowel disease flare (where delayed anti-inflammatory therapy increases complications). The catch: the same patient may have both—for example, an ulcerative colitis flare triggered by Clostridioides difficile or superimposed bacterial dysentery. Your goal in the first 48 hours is to stabilise, risk-stratify, exclude dangerous infections, and pick a direction for therapy that you can defend with data. ^[1–6]

Hour 0–1: Stabilise, isolate, and triage red flags

1. Airway–Breathing–Circulation and sepsis screen. Treat shock first; obtain large-bore access and send labs with the first blood draw. ^[1,5]
2. Contact precautions if you suspect C. difficile, shiga-toxin producing E. coli (STEC), or norovirus. ^[1,4]
3. Red flags that dictate setting and pace: hypotension, severe dehydration, syncope, peritonitis, toxic megacolon suspicion, hemoglobin <8–9 g/dL with ongoing bleeding, immunosuppression (steroids, biologics), pregnancy, advanced age with comorbidities. ^[1–3,5]
4. Core history (fast, focused): recent antibiotics; hospitalisation or long-term care; immunosuppressants/biologics; travel; undercooked meat, unpasteurised dairy, raw produce; sexual exposures (e.g., MSM networks and Shigella), sick contacts, freshwater exposure, onset and tempo; baseline IBD activity and past flare patterns. ^[1–3]

Hour 0–6: Order once, order right

Baseline labs (stat when unstable; routine otherwise)

• CBC with differential, CRP (and/or ESR), CMP including creatinine, electrolytes, liver enzymes; lactate if septic concern. ^[1–3]
• Pregnancy test in people who could be pregnant.
• Inflammatory bowel disease context: If known IBD, obtain trough levels for biologics when relevant (do not delay urgent care for this). ^[5,6]

Stool testing strategy (adult acute bloody diarrhea)

• Multiplex stool PCR panel that covers bacterial pathogens (e.g., Shigella, Salmonella, Campylobacter, Yersinia), shiga toxin genes, and key viruses/parasites as per your lab’s platform. Faster turn-around and higher sensitivity than culture alone. Interpret positives in clinical context; some panels detect DNA from nonviable organisms. ^[1–3]
• Shiga toxin test (gene by PCR and/or EIA for toxin) with reflex culture to identify STEC serotype. Avoid antibiotics and antimotility drugs if STEC is suspected (bloody diarrhea with severe cramps, afebrile, after beef/salad exposure) due to hemolytic uremic syndrome risk. ^[1–3]
• C. difficile testing if there is recent antibiotic use, health-care exposure, or IBD, even if community-onset. Follow your lab’s algorithm (NAAT/toxin or multistep testing). ^[4,5]
• Ova and parasite testing for persistent symptoms, travel, or community outbreaks, or when panel lacks parasites. ^[1–3]

Do not shotgun empiric therapy. Early, targeted results reduce unnecessary antibiotics that may worsen outcomes (e.g., STEC) or muddy the IBD picture. ^[1–4]

Interpreting early clues: infection or flare?

There is no single perfect discriminator. Use pattern recognition plus tests you can get within 48 hours.

Clinical patterning (helpful, not diagnostic)

• Infectious enterocolitis: abrupt onset, fever, severe cramps, sick contacts or travel, outbreak foods; right-sided pain (e.g., Campylobacter/Yersinia), marked tenesmus with Shigella; sometimes afebrile with STEC. ^[1–3]
• Ulcerative colitis flare: gradual worsening of established symptoms, rectal bleeding with urgency and tenesmus, continuous disease from rectum proximally; fever less typical unless severe. ^[5,6]
• Crohn’s disease flare: focal or segmental pain; right lower quadrant common; weight loss over weeks; perianal disease or fistulae. ^[5,6]

Fecal calprotectin (useful but overlapping)

markedly elevated values (e.g., >250–300 μg/g) support active intestinal inflammation, but both infection and IBD flare can produce high results. A very low calprotectin (<50 μg/g) argues against IBD activity, but it does not exclude infectious colitis early. Use it to support, not to decide in isolation. ^[7–9]

CRP and leukocytosis

can be high in either infection or severe flare; trend with the clinical picture. ^[1–3,5]

Imaging in the first 24 hours—when and why

• CT abdomen/pelvis with IV contrast is appropriate in moderate–severe illness, peritonitis concern, severe pain disproportional to exam, or when complications (toxic megacolon, perforation, abscess) are possible. ^[1,5,6]
• Patterns that nudge the differential: continuous, left-sided colitis from rectum favors ulcerative colitis; segmental/right-sided or ileocecal involvement suggests infectious colitis or Crohn’s disease; prominent fat stranding, comb sign, strictures, or fistulae lean Crohn’s. Ischemic colitis gives segmental “watershed” patterns (consider in older or vasculopathic patients). These are not absolute but useful when combined with labs and history. ^[5,6,10]

Endoscopy in the first 48 hours—scope with intent

• In known or suspected severe ulcerative colitis, a limited flexible sigmoidoscopy with minimal insufflation and biopsies can confirm active colitis, obtain C. difficile toxin cytology, and check for cytomegalovirus in immunosuppressed patients. Avoid full colonoscopy in toxic colitis. ^[5,6,11]
• In undifferentiated acute severe disease with significant bleeding, scope decisions depend on stability, imaging, and surgeon backup. If you scope, keep it limited and diagnostic—the goal is not mucosal healing photography; the goal is yes/no questions that change management. ^[5,6,11]

Antibiotics: when to start, when to hold

• Start empiric antibiotics when the patient is systemically ill, septic, or high-risk dysentery consistent with Shigella (fever, abdominal pain, tenesmus) while cultures/PCR are pending—azithromycin is commonly used where resistance allows; local susceptibility patterns matter. ^[1–3,12]
• Hold antibiotics when STEC is likely (bloody diarrhea after beef/leafy greens, severe cramps, little or no fever) until shiga toxin testing returns. Antibiotics and loperamide increase hemolytic uremic syndrome risk in STEC. ^[1–3]
• Avoid fluoroquinolones where resistance is high or risks outweigh benefits; prefer azithromycin for traveler-associated febrile dysentery in many regions. ^[1–3,12]
• C. difficile: if positive, treat per updated IDSA/SHEA guidance (fidaxomicin or vancomycin first-line in most adults) and de-escalate other antibiotics where safe. ^[4]

Corticosteroids and advanced IBD therapy: start only when you can defend it

• In a known ulcerative colitis flare that is moderate–severe, hospitalised, and dangerous infections are reasonably excluded (negative C. difficile, no STEC suspicion, no red flags for invasive bacterial disease), initiate systemic corticosteroids per guideline dosing. Document your infection screen. ^[5,6,11]
• In Crohn’s disease, exclude abscess before starting systemic steroids; CT or MRI enterography if concern persists. ^[5,6]
• Do not escalate to biologics or small molecules (for example, infliximab, cyclosporine, JAK inhibitors) until infection exclusion is adequate and surgical catastrophe is off the table. ^[5,6,11]

The 48-hour playbook (step-by-step)

Hours 0–6

• Resuscitate if needed; place on enteric precautions.
• Send CBC, CRP/ESR, CMP, lactate (if sick); pregnancy test if applicable.
• Order stool multiplex PCR with shiga toxin and reflex culture; add C. difficile test when risk or IBD is present.
• Decide on empiric antibiotics only if severe sepsis or high-likelihood bacterial dysentery without STEC phenotype.
• Get CT if red flags/complications suspected. ^[1–6]

Hours 6–24

• Review lab trends; begin targeted antibiotics if a treatable invasive pathogen is identified; withhold if STEC suspected/confirmed.
• If known severe ulcerative colitis and infections are unlikely/ruled out, start systemic steroids per guideline.
• Limited flexible sigmoidoscopy (with biopsies) if it will change management (e.g., confirm severe UC, assess for CMV). ^[4–6,11]

Hours 24–48

• Act on stool PCR results (de-escalate empiric antibiotics when not indicated).
• If improving on supportive care/targeted therapy, continue and plan follow-up.
• If no improvement and infection ruled out, escalate IBD therapy per severity algorithms (consider rescue therapy for severe UC).
• Consult surgery early in toxic colitis, megacolon, or refractory bleeding. ^[5,6,11]

Pearls and pitfalls you will remember on call

• Both can be true: infection can precipitate a flare. Treat the infection and the inflammation—document timing and rationale. ^[4–6]
• Do not rely on fever: afebrile STEC presents with impressive hematochezia. ^[1–3]
• Antimotility agents can worsen outcomes in invasive dysentery and STEC; avoid until you know what you are treating. ^[1–3]
• Calprotectin is a volume knob, not a light switch: high supports inflammation but does not distinguish etiology; low supports a non-inflammatory process. ^[7–9]
• Flexible sigmoidoscopy beats “blind” steroid starts in severe UC—when safe and feasible. ^[5,6,11]
• Think ischemia in older patients with vascular disease and sudden left-sided pain plus bleeding; management differs. ^[10]
• In IBD on biologics with severe flare, do not forget CMV (biopsy for immunohistochemistry or PCR on tissue). ^[11]

Disposition and follow-up

• Admit if unstable, high-volume bleeding, severe dehydration, significant anemia, toxic colitis, or if the home setting is unsafe. ^[5,6,11]
• Outpatient management is reasonable in clinically stable patients with reliable follow-up and no red flags—document return precautions (worsening bleeding, syncope, fever, severe pain).
• Post-episode review (7–14 days): reconcile antibiotics, re-assess need for steroid taper, optimise IBD maintenance therapy, and update vaccines if antibiotics or steroids were used. ^[4–6]

For searchers and skimmers: concise answers to common queries

How do you tell infectious enterocolitis from an ulcerative colitis flare in the emergency department?

Use exposure history, PCR-based stool testing (including shiga toxin and C. difficile), inflammation markers, and imaging when indicated. Consider limited sigmoidoscopy in severe suspected ulcerative colitis. Begin steroids only after dangerous infections are excluded. ^[1–6,11]

What is the role of fecal calprotectin in acute bloody diarrhea?

It confirms mucosal inflammation but does not distinguish infection from flare reliably; interpret alongside stool results and the clinical picture. ^[7–9]

When are antibiotics appropriate?

Start empirically for severe sepsis or likely bacterial dysentery (not for STEC). De-escalate to pathogen-directed therapy when results return. Treat C. difficile per guideline. ^[1–4,12]

When do you scope?

Early flexible sigmoidoscopy with biopsies in severe ulcerative colitis or when results will change management (e.g., CMV). Avoid full colonoscopy in toxic colitis. ^[5,6,11]

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