In a 22‑year‑old patient with aplastic anemia who underwent an allogeneic bone‑marrow transplant and is now day 13 post‑transplant with fever, diarrhea, tachycardia, abdominal distension, and intermittent nausea/vomiting after earlier severe nausea/vomiting, hematemesis, nil per os status, nasogastric tube placement, and treatment with colistin, ceftazidime‑avibactam (Zavicefta) and aztreonam for a procalcitonin >100, what is the appropriate management?

Management of Day 13 Post-BMT Complications in Aplastic Anemia Patient

This patient requires immediate evaluation for acute graft-versus-host disease (GVHD) of the gastrointestinal tract, with concurrent assessment for infectious complications including CMV colitis, and consideration of empiric antifungal therapy given persistent fever beyond 4-7 days of antibacterial treatment. 1

Immediate Diagnostic Workup

Obtain the following studies urgently:

• Complete blood count with differential, comprehensive metabolic panel, and liver function tests to assess engraftment status, renal function, and hepatic involvement 2
• Blood cultures (bacterial and fungal), urine cultures, and stool studies including Clostridium difficile toxin, bacterial culture, and viral PCR panel 2
• CMV quantitative PCR from blood – this is critical as the patient is in phase II post-transplant (day 13) when CMV reactivation is a dominant pathogen causing colitis and hepatitis 1, 2
• Chest CT scan given persistent fever beyond day 3 of broad-spectrum antibiotics to evaluate for invasive fungal infection, particularly Aspergillus 1
• Stool calprotectin or lactoferrin if available, and consider flexible sigmoidoscopy with biopsy if the patient is stable enough, as this can differentiate GVHD from infectious colitis 1

Infection Risk Stratification

This patient is in Phase I-II transition (day 13 post-BMT), characterized by: 1, 2

• Phase I (preengraftment, <30 days): Prolonged neutropenia and mucosal barrier breakdown dominate, with bacterial and fungal pathogens (Candida, Aspergillus) being primary concerns 1
• Phase II (30-100 days): Impaired cell-mediated immunity emerges, with CMV, Pneumocystis jirovecii, and Aspergillus as key pathogens 1, 2

The patient's allogeneic BMT for aplastic anemia places him at high overall infection risk requiring fluoroquinolone prophylaxis during neutropenia, antifungal prophylaxis, PCP prophylaxis, and viral prophylaxis 1

Antimicrobial Management

Current Antibacterial Therapy Assessment

• Continue colistin, ceftazidime-avibactam (Zavicefta), and aztreonam as these provide broad coverage including multidrug-resistant gram-negatives given the procalcitonin >100 1
• Add empiric antifungal therapy immediately since fever persists beyond 4-7 days despite antibacterial therapy 1, 2
• Preferred empiric antifungal: Caspofungin (70 mg loading dose, then 50 mg daily) or micafungin, as these provide coverage for Candida and Aspergillus species 1, 3

CMV Management

If CMV PCR is positive (≥2 consecutive samples): 1, 4

• First-line treatment: Oral valganciclovir 900 mg twice daily (adjusted for renal function) OR intravenous ganciclovir 5 mg/kg twice daily if concerns about absorption exist given the GI symptoms 1, 4
• Continue treatment for at least 2 weeks and until CMV is no longer detectable by PCR 1, 4
• Monitor weekly CMV viral load during treatment 1, 4
• If ganciclovir-resistant or intolerant (myelosuppression): Consider foscarnet, though this carries nephrotoxicity risk, or maribavir for refractory cases with infectious disease consultation 1, 4

Important caveat: Letermovir is used for prophylaxis (480 mg daily, or 240 mg if on cyclosporine) through day 100-200 post-transplant but is NOT used for treatment of active CMV disease 1, 5

HSV/VZV Prophylaxis

• Continue acyclovir, valacyclovir, or famciclovir for HSV/VZV prophylaxis regardless of CMV treatment, as these agents have weak activity against CMV 1, 4, 2

GVHD Evaluation and Management

Acute GVHD is a critical differential diagnosis given the timing (day 13), diarrhea, nausea/vomiting, and abdominal distension: 1

Clinical Assessment

• Acute GVHD typically manifests between days 20-47 but can occur as early as day 13, particularly in allogeneic BMT recipients 1, 6
• GI GVHD presents with: Diarrhea (often high-volume, secretory), nausea, vomiting, abdominal pain, and distension 1
• Differentiate from infectious colitis through endoscopy with biopsy showing apoptotic bodies in crypts (GVHD) versus inflammatory infiltrates or viral inclusions (infection) 1

GVHD-Specific Infection Prophylaxis

If GVHD is confirmed, intensify infection prophylaxis: 1, 2

• Antibacterial: Continue fluoroquinolone prophylaxis 1, 2
• PCP prophylaxis: Trimethoprim-sulfamethoxazole (preferred) or alternative if contraindicated 1, 2
• Antifungal: Fluconazole or micafungin until at least day 75 post-transplant 1, 2
• CMV monitoring: Weekly quantitative PCR with preemptive therapy 1, 2

Nutritional Support

Given NPO status, nasogastric tube placement, and ongoing GI symptoms: 1

• Maintain adequate nutritional intake through enteral nutrition (EN) if tolerated, or parenteral nutrition (PN) if EN is insufficient or contraindicated 1
• Contraindications to EN in this patient: Severe mucositis, intractable vomiting, ileus, severe malabsorption, protracted diarrhea, or symptomatic GI GVHD 1
• If these contraindications exist, initiate PN immediately to prevent further weight loss and body cell mass depletion, which negatively impacts clinical outcomes 1
• PN with high long-chain fatty acid content may reduce lethal acute GVHD rates in allogeneic BMT recipients 1

Antiemetic Management

For persistent nausea and vomiting on day 13 post-BMT: 1

• Three-drug combination: NK₁ receptor antagonist (aprepitant), 5-HT₃ receptor antagonist (ondansetron or granisetron), and dexamethasone 1
• This regimen significantly reduces vomiting in high-dose chemotherapy and stem cell transplant recipients (complete response 58% vs 41% with placebo, P=0.004) 1

Critical Monitoring Parameters

Daily assessment should include: 1, 2

• Vital signs with focus on fever curve, tachycardia, and hemodynamic stability 2
• Stool output volume and character to differentiate secretory (GVHD) from infectious diarrhea 1
• Complete blood count to monitor for neutropenia (ganciclovir toxicity), thrombocytopenia, and engraftment status 1, 2
• Renal function and electrolytes especially if foscarnet is used (nephrotoxicity, electrolyte abnormalities) 1, 4
• Weekly CMV viral load during treatment 1, 4

Common Pitfalls to Avoid

• Do not delay empiric antifungal therapy beyond 4-7 days of persistent fever despite antibacterials – this increases mortality 1, 2
• Do not use acyclovir or valacyclovir for CMV treatment – they have weak anti-CMV activity and are inadequate 4
• Do not discontinue HSV/VZV prophylaxis when starting letermovir or treating CMV with ganciclovir/valganciclovir 1, 4, 5
• Do not assume all diarrhea is infectious – acute GVHD is a critical differential requiring different management 1
• Do not use oral valganciclovir if substantial GI GVHD is present – absorption is unreliable; use IV ganciclovir instead 1