Question 21

College Answer

21.1      Outline     methods     for     diagnosing     CMV     infection     in     the     critically     ill immunocompetent  patient.

•    Viral cultures: Obsolete because of low sensitivity and time consuming nature.
•    Antigenemia: Direct detection of CMV protein pp65 using monoclonal antibodies.
Sensitive, quantitative but requires sufficient white cells in peripheral blood.
•    PCR assays: High sensitivity and rapid turnover time but not standardised.

21.2      List risk factors for CMV infection in the above patient group.

•    Mechanical ventilation.
•    Bacterial pneumonia and sepsis.
•    Corticosteroid use: Not clear.
•    Red cell transfusion: Immunomodulatory  effect of transfusion, rather than potential transmission of CMV.
•    Burns patients: Cell mediated immunity and T–helper 1 cells increase infection.

21.3      List the effects of CMV infection on outcomes in immunocompetent  patients.

•    Organ dysfunction: Increased  liver and renal failure.
•    Severe CMV disease: Pneumonitis, pneumonia, neurologic disease.
•    ICU stay prolonged
•    Mechanical ventilation duration increased
•    Increased incidence of bacterial or fungal infection
•    Mortality possibly increased

21.4      List drugs available for treating CMV infections.

•    Ganciclovir / valganciclovir.
•     Foscarnet.
•     Cidofovir.

Discussion

The topic of cytomegalovirus infection is explored in greater detail somewhere in the Required reading section.

To answer the question:

Diagnosis

These days, the diagnosis of CMV rests on the following tests:

• Positive CMV antibodies (IgM) - sensitive for recent or acute infection
• Qualitative PCR - very sensitive for the presence of CMV, but they do not distingusih between active and latent infection.
• Quantitative PCR - ideal test, as it provides a quantitative assessment of viral load, and allows the monitoring of therapy.

Risk factors for the immunocompetent host (among the ICU population)

Critical illness in general seems to be a risk factor.

Searching through the references, one can find the following risk factors for reactivation:

• Trauma
• Burns
• Severe critical illness (high APACHE score, over 27)
• Blood transfusion
• Mechanical ventilation
• Severe sepsis
• Prolonged ICU stay
• Pregnancy

Consequences of CMV reactivation

The consequences of CMV in the immunocompetent host are detailed in an excellent article on this topic, published in 1997. For the paying customer, UpToDate also has a summary of CMV complications. In short, these complications consist of the following:

• Colitis
• Hepatitis
• Encephalitis
• Guillain-Barre syndrome
• Pneumonitis (rare)
• Pericarditis and myocarditis
• Uveitis and retinitis

The college asks specifically about "outcomes". Some of the abovementioned complications can degrade cardiopulmonary performance and thus increase the duration of ventilation and length of ICU stay. Plus, the profound lethargy associated with CMV infection frustrates everything, from physiotherapy to ventilator weaning.

Indirect Consequences of CMV infection 
(from this 2013 article)

Immunocompetent host Bacterial sepsis Fungal sepsis Cardiovascular disease Prolonged ventilation Prolonged ICU stay Increased mortality from all causes

Immunocompromised (transplant) host Chronic allograft nephropathy (renal transplant) Hepatic artery thrombosis (liver transplant) Accelerated Hep C recurrence (liver transplant) Bronchiolitis obliterans (lung transplant) New onset NIDDM Post-transplant lymphoproliferative disease

Management of CMV infection

Ganciclovir, valganciclovir, foscarnet and cidofovir are the recommended antiviral agents.

The most recent guidelines recommend one start with ganciclovir, and convert to valganciclovir when the infection is under control. Foscarnet and cidofovir are reserved for ganciclovir-resistant mutants, owing to their nightmarish toxicity.

 

Chou, Suowen. "Newer methods for diagnosis of cytomegalovirus infection." Review of Infectious Diseases 12.Supplement 7 (1990): S727-S736.

Razonable, Raymund R., and Randall T. Hayden. "Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation."Clinical microbiology reviews 26.4 (2013): 703-727.

Vancikova, Z., and P. Dvorak. "Cytomegalovirus infection in immunocompetent and immunocompromised individuals--a review." Current drug targets. Immune, endocrine and metabolic disorders 1.2 (2001): 179-187.

Eddleston, M., et al. "Severe cytomegalovirus infection in immunocompetent patients." Clinical infectious diseases 24.1 (1997): 52-56.

Andrews, Peter A., Vincent C. Emery, and Chas Newstead. "Summary of the British Transplantation Society guidelines for the prevention and management of CMV disease after solid organ transplantation." Transplantation 92.11 (2011): 1181-1187.

Kotton, Camille N., et al. "Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation." Transplantation96.4 (2013): 333-360.

Jacobson, Mark A. "Review of the toxicities of foscarnet." JAIDS Journal of Acquired Immune Deficiency Syndromes 5 (1992): S11-17.

Lalezari, Jacob P., et al. "Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS." JAIDS Journal of Acquired Immune Deficiency Syndromes 17.4 (1998): 339-344.