Critical Care Medicine-Infections and Immunologic Disease>>>>>Infections in the Immunocompromised Host
Question 5#

A 62-year-old male who underwent bilateral lung transplantation (CMV donor positive/recipient negative, EBV donor positive/recipient negative) for end-stage lung disease due to chronic obstructive pulmonary disease is admitted to the ICU with left lower quadrant abdominal pain, diarrhea, and hypotension. His symptoms started 5 days ago and have been progressively worsening. Diarrhea is mainly watery and frequency ranges from four to five times per day. On examination, the patient was afebrile with blood pressure 84/60 mm Hg, heart rate of 100 beats per minute, and dry oral mucosa. His abdomen was diffusely tender to palpation. An x-ray of the abdomen demonstrated colonic ileus with no evidence of gas under the diaphragm. Stool Clostridium difficile PCR, stool ova and parasites testing, and stool cultures are negative. CMV is undetectable by PCR in the plasma.

What is the next BEST step in managing this patient?

A. CT scan of the abdomen with contrast
B. Colonoscopy and biopsies
C. Check serum EBV quantitative viral load
D. 24-hour stool fat test
E. Empiric treatment with micafungin and valganciclovir

Correct Answer is B

Comment:

Correct Answer: B

This patient with a discordant CMV serology status (donor positive, recipient negative) presenting with diarrhea is most likely to have CMV tissue-invasive disease and colitis despite a negative plasma CMV PCR. Tissue biopsies from multiple sites in the colon showing characteristic histopathology are needed to confirm the diagnosis.

CMV is a member of Herpesviridae genus that causes life-threatening infection in both solid organ transplant and hematopoietic stem cell transplant recipients. The virus can cause primary infection that occurs in seronegative patients or secondary infection, usually attributed to reactivation of latent infection. Primary infections are usually more severe than secondary infections.

Plasma CMV PCR can be negative in 15% of tissue-invasive CMV colitis. In patients with compartmentalized CMV disease like colitis, viremia may be very low or transient. Thus, biopsy is needed to confirm the diagnosis. CMV replicates within the nuclei of infected cells which is represented by the large eosinophilic intranuclear inclusion bodies on hematoxylin and eosin staining of tissue samples. There may be associated tissue necrosis and endothelial damage. 

However, repeat colonoscopy with biopsy is not required to document clearance after appropriate antimicrobial treatment is completed. A computed tomography (CT) scan of the abdomen is not diagnostic in CMV colitis. Empiric therapy is not indicated in suspected colitis without viremia as ganciclovir treatment is associated with significant marrow toxicity. 

References:

  1. Razonable RR, Humar AA. Cytomegalovirus in solid organ transplantation. Am J Transplant. 2013;13(suppl 4):93-106.
  2. Razonable RR, Hayden RT. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin Microbiol Rev. 2013;26(4):703-727.