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

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

Guillain-Barre Syndrome (see Guillain-Barre Syndrome, [[Guillain-Barre Syndrome]])

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

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

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

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)

Ganciclovir (see Ganciclovir, [[Ganciclovir]]): 5 mg/kg IV q12 hrs x 14-21 days + Intravenous Immunoglobulin (IVIG) (see Intravenous Immunoglobulin, [[Intravenous Immunoglobulin]])

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

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

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

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]