How should I urgently evaluate and manage possible acute gastrointestinal graft‑versus‑host disease in a 22‑year‑old with aplastic anemia who is day 13 after an allogeneic bone‑marrow transplant and now has fever, severe diarrhea, abdominal distension, nausea/vomiting, and tachycardia while receiving colistin, ceftazidime‑avibactam and aztreonam for a markedly elevated procalcitonin?

Urgent Evaluation and Management of Suspected Acute GI GVHD Post-Transplant

This patient at day 13 post-allogeneic BMT with severe diarrhea, fever, abdominal distension, nausea/vomiting, and tachycardia requires immediate aggressive management as complicated acute GI GVHD with concurrent sepsis risk, including IV fluids, octreotide, continuation of broad-spectrum antibiotics, comprehensive stool workup, endoscopic biopsy, and empiric systemic corticosteroids while ruling out infectious etiologies. 1

Critical Context: Phase I Post-Transplant Risk

• At day 13 post-HSCT, this patient is in Phase I (preengraftment, <30 days), characterized by prolonged neutropenia and mucocutaneous barrier breakdown, making bacterial and fungal pathogens from GI/skin flora the primary infectious threats 1
• During preengraftment, fever is most likely bacterial, though organisms are rarely identified, necessitating empiric treatment until neutropenia resolves 1, 2
• The markedly elevated procalcitonin with fever and tachycardia suggests bacterial sepsis, which carries exceptionally high mortality risk in this population 2

Immediate Classification: Complicated CTID/GVHD

This patient meets criteria for "complicated" disease requiring aggressive management: 1

• Grade 3-4 diarrhea (severe volume)
• Fever (suggesting infection/sepsis)
• Abdominal distension and nausea/vomiting (suggesting ileus or severe mucosal injury)
• Tachycardia (suggesting dehydration/sepsis)
• Neutropenia in Phase I post-transplant

Urgent Diagnostic Workup

Stool Studies (Priority #1)

• Comprehensive stool testing for bacterial pathogens: Salmonella, E. coli (including STEC O157), Campylobacter, Shigella 1, 3
• Clostridium difficile toxin assay 1
• Fecal leukocytes and occult blood 1, 3
• Stool volume quantification if feasible 1

Viral Reactivation Testing

• CMV PCR (blood and stool) - CMV causes colitis in Phase II but can occur earlier with GVHD 1
• Consider HSV, adenovirus, norovirus testing 1

Laboratory Assessment

• Complete blood count with differential (assess neutropenia, thrombocytopenia, schistocytes) 1, 3
• Comprehensive metabolic panel (electrolytes, renal function, liver function) 1
• Repeat procalcitonin, blood cultures 2

Imaging

• Abdominal CT with contrast to evaluate for neutropenic enterocolitis (typhlitis), bowel wall thickening, perforation, or abscess 1, 3

Endoscopic Evaluation with Biopsy

• Rectosigmoid biopsy has highest sensitivity and negative predictive value for GI aGVHD, regardless of whether patient presents with diarrhea, nausea, or vomiting 1
• Biopsy should be performed as clinically indicated to confirm aGVHD before escalating immunosuppression, though pathologic confirmation is not absolutely required if clinical suspicion is high 1
• Obtain biopsies from multiple GI sites if endoscopy performed (upper and lower) 1

Immediate Therapeutic Interventions

Aggressive Supportive Care (Initiate Immediately)

• IV fluid resuscitation for dehydration and hemodynamic instability 1
• Octreotide 100-150 mcg SC three times daily or IV infusion (25-50 mcg/hour) if severely dehydrated, with dose escalation up to 500 mcg until diarrhea controlled 1
• NPO status with bowel rest initially 1
• Electrolyte repletion (particularly potassium, magnesium) 1

Antibiotic Management

• Continue current broad-spectrum antibiotics (colistin, ceftazidime-avibactam, aztreonam) given markedly elevated procalcitonin and sepsis concern 2
• The current regimen provides excellent gram-negative coverage including Pseudomonas and resistant organisms 2
• Consider adding empiric gram-positive coverage (vancomycin or linezolid) if not already on board, given central line and mucosal barrier breakdown 1, 2
• Do NOT discontinue antibiotics pending stool studies - bacterial septicemia carries exceptionally high mortality in Phase I post-transplant 2

Empiric Systemic Corticosteroids for aGVHD

• Initiate methylprednisolone 2 mg/kg/day IV (or prednisone 2 mg/kg/day PO if able to tolerate oral) as first-line therapy for presumed severe (grade III-IV) GI aGVHD 1, 4
• This should be started empirically given high clinical suspicion, severity of presentation, and poor prognosis without treatment 1, 4
• Continue until diarrhea-free for 24 hours, then begin slow taper 1

Immunosuppression Adjustment

• Continue or restart baseline GVHD prophylaxis agents (typically calcineurin inhibitor) 1
• Do not taper immunosuppression during acute episode 1

Critical Pitfalls to Avoid

1. Delaying broad-spectrum antibiotics or narrowing coverage prematurely - bacterial septicemia is fatal in Phase I neutropenia 2
2. Withholding steroids pending biopsy confirmation - severe GI aGVHD has poor prognosis without prompt treatment, and biopsy is not absolutely sensitive 1, 4
3. Relying solely on loperamide for grade 3-4 diarrhea - octreotide is more effective for severe cases 1
4. Inadequate fluid resuscitation - severe diarrhea causes profound volume depletion 1
5. Missing CMV reactivation - CMV causes colitis and potentiates superinfection, particularly with active GVHD 1

Monitoring and Reassessment

• Monitor stool output, vital signs, and fluid balance every 4-6 hours 1
• Daily electrolytes, CBC, liver function tests 1
• Reassess clinical response to steroids at 3-5 days 1
• If no response to first-line steroids by day 5-7, consider steroid-refractory aGVHD and second-line therapy with ruxolitinib (JAK2 inhibitor) 5
• If fever persists after 4-7 days of appropriate antibacterial therapy, add empiric antifungal coverage and obtain chest CT for invasive aspergillosis 2

Disposition and Multidisciplinary Care

• Immediate ICU consultation if hemodynamically unstable or signs of shock 1
• Transplant team coordination for GVHD management 1
• Gastroenterology consultation for endoscopy timing and GI bleeding management if develops 4
• Infectious disease consultation for complex antibiotic management 2
• Nutrition consultation for TPN if prolonged NPO status required 1, 4