Cytomegalovirus (CMV)

  • Recent reports suggest that CMV reactivation is not infrequent in complicated ICU patients with prolonged courses. PCR/antigen assays are more sensitive than viral cultures for detecting reactivation
  • Although CMV reactivation has been associated with increased ICU mortality, causality has not been established
  • At this time, there is no role for prophylactic therapy in patients with positive serology, as the majority of these patients will probably not reactivate

  • In a recent prospective study of 256 non-immunocompromised adult patients admitted to the ICU, it was found that there was a significantly increased length of stay (32 vs 12 days) for those who contracted CMV

  • This has been consistently reported in many other studies
  • A non-statistically significant increase in mortality was reported in most studies
  • Older age, prior stay in hospital wards, and recent corticosteroid use prior to admission were associated with CMV infection
  • 87% were seropositive on admission, indicating a reactivation during the ICU stay
  • The CMV infection was highest in burn ICUs, followed by trauma, medical, and cardiac critical care units

Epidemioloogy

Risk Factors

  • Organ Transplant: occurs most commonly 1-3 months post-transplant
  • Post-Allogeneic Bone Marrow Transplant (BMT)/Stem Cell Transplant (SCT): CMV is the most common and most lethal type of pneumonia
    • Greatest risk of CMV pneumonia is 30-90 days post-BMT
    • 80% of these patients with diffuse pulmonary infiltrates have Bx-proven CMV infection
    • Risk Factors
      • Advanced Age
      • Acute Graft vs Host Disease (GVHD) (see Graft vs Host Disease, [[Graft vs Host Disease]])
      • Intensive Conditioning Regimens
      • Allograft: CMV (and Toxoplasmosis) occur far less commonly in auto-BMT/SCT, as compared to allo-BMT/SCT -> CMV occurs in <2% of auto-SCT cases
  • AIDS (see Human Immunodeficiency Virus, [[Human Immunodeficiency Virus]]): CMV penumonitis is relatively less common in AIDS than in organ transplants (due probably to impaired cytotoxic response)
  • Immunocompetent: few cases in normals without known immune defect
  • Anti-CD20 Therapy (see Anti-CD20 Therapy, [[Anti-CD20 Therapy]]): possible risk factor

Diagnosis

  • xxx

Clinical Presentations

General Comments

  • CMV infection is usually a generalized infection

Dermatologic Manifestations

Neurologic Manifestations

Ophthalmologic Manifestations

  • CMV Retinitis: in AIDS

Otolaryngologic Manifestations

  • Heterophil Ab-Negative Mononucleosis Syndrome with Non-Exudative Pharyngitis (see Pharyngitis, [[Pharyngitis]]): may be prolonged
  • Oral Ulcerations (see Oral Ulcers, [[Oral Ulcers]])
    • Epidemiology: occurs in AIDS

Pulmonary Manifestations

CMV Interstitial Pneumonitis (see Interstitial Lung Disease-Etiology, [[Interstitial Lung Disease-Etiology]])

  • Diagnosis
    • ABG: hypoxemia (marker for life-threatening CMV infection)
    • FOB: culture of CMV does not indicate active infection (but culture is more sensitive than histologic examination)
      • BAL or TBB: may show “cytomegalic” alveolar epithelial cells or alveolar macrophages with characteristic oval “owl’s eye” intranuclear inclusions and intra-cytoplasmic inclusions
    • CXR/Chest CT patterns
      • Bilateral mid-lower zone interstitial infiltrates: may be perihilar (mimicking pulmonary edema)
      • Miliary pattern: tend to have rapidly progressive course
  • Clinical
    • Fever (see Fever, [[Fever]])
    • Dry Cough (see Cough, [[Cough]])
    • Dyspnea (see Dyspnea, [[Dyspnea]])
    • Rales

Acute Lung Injury-ARDS (see Acute Lung Injury-ARDS, [[Acute Lung Injury-ARDS]])

  • xxx

Pleural Effusion (see Pleural Effusion-Exudate, [[Pleural Effusion-Exudate]])

  • xxx

Other Manifestations

  • xxx

Effect of Immune Reconstitution Syndrome

  • Immune reconstitution usually occurs within 6 months after start of HAART therapy and may paradoxically worsen CMV disease

Treatment

Acute Treatment of CMV Retinitis, Gastrointestinal Disease, or Pneumonia in Non-Bone Marrow Transplant Patient

  • Ganciclovir (see Ganciclovir, [[Ganciclovir]]): 5 mg/kg IV q12 hrs x 14-21 days
    • Adverse Effects
      • Neutropenia
      • Thrombocytopenia
      • Acute Kidney Injury (AKI)
      • Central Nervous System Toxicity
      • Mutagenicity
      • Carcinogencitiy
      • Teratogenicity
  • Valganciclovir (Valcyte) (see Valganciclovir, [[Valganciclovir]]): 900 mg PO BID x 21 days
    • Valganciclovir (a prodrug that is converted to ganciclovir) achieves plasma levels close to that of IV gancicovir
  • Foscarnet (see Foscarnet, [[Foscarnet]]): 60 mg/kg IV q8 hrs x 14-21 days
    • Useful for ganciclovir-resistant CMV
    • Adverse Effects
      • Acute Kidney Injury (AKI) (see Acute Kidney Injury, [[Acute Kidney Injury]])
      • Hypocalcemia/Hypercalcemia
      • Hypomagnesemia
      • Hypokalemia
      • Hypophosphatemia/Hyperphosphatemia
      • Central Nervous System Toxicity
      • Gential Ulcerations
  • Cidofovir (Vistide) (see Cidofovir, [[Cidofovir]]): 5 mg/kg IV weekly x 2 wks
    • Adverse Effects: acute kidney injury (need to hydrate and use with probenecid)

CMV Pneumonia in Bone Marrow Transplant Patient

Chronic Suppression of CMV Retinitis in AIDS/Immunocomromised Patient

  • Ganciclovir (see Ganciclovir, [[Ganciclovir]]): 5mg/kg/day IV or 6 mg/kg IV 5x per wk or 1 g PO TID
  • Valganciclovir (Valcyte) (see Valganciclovir, [[Valganciclovir]]): 900 mg PO qday
  • Foscarnet (see Foscarnet, [[Foscarnet]]): 90-120 mg/kg/day IV
  • Cidofovir (Vistide) (see Cidofovir, [[Cidofovir]]): 5 mg/kg IV q2 wks

Intraocular Therapy for Retinitis

  • Ganciclovir Implant (see Ganciclovir, [[Ganciclovir]])
  • Intravitreal Fomivirsen

Prevention of CMV in AIDS

  • Ganciclovir (see Ganciclovir, [[Ganciclovir]]): 1 g PO TID
    • PO ganciclovir has only 5-10% bioavailability

Prevention of CMV in Transplants

  • Ganciclovir (see Ganciclovir, [[Ganciclovir]]): 5 mg/kg IV q12 hrs x 7-14 days, then 5 mg/kg IV qday or 6 mg/kg IV 5x per wk
  • Ganciclovir (see Ganciclovir, [[Ganciclovir]]): 1 g PO TID

References

  • Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA 2008;300(4):413-22
  • Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients. Crit Care Med 2009;37:1850-57
  • Cytomegalovirus in the intensive care unit: pathogen or passenger? Crit Care Med 2009;37(6):2095-96
  • Prevalence and mortality with cytomegalovirus infection in nonimmunosuppressed patients in the intensive care unit. Crit Care Med 2009;37:2350-58
  • Valganciclovir for the Prevention of Complications of Late Cytomegalovirus Infection After Allogeneic Hematopoietic Cell Transplantation: A Randomized Trial. Ann Intern Med. 2015 Jan 6;162(1):1-10. doi: 10.7326/M13-2729 [MEDLINE]