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Cytomegalovirus Reactivation in Critically Ill Immunocompetent Patients
Ajit P. Limaye, MD;
Katharine A. Kirby, MSc;
Gordon D. Rubenfeld, MD;
Wendy M. Leisenring, ScD;
Eileen M. Bulger, MD;
Margaret J. Neff, MD;
Nicole S. Gibran, MD;
Meei-Li Huang, PhD;
Tracy K. Santo Hayes, BSc;
Lawrence Corey, MD;
Michael Boeckh, MD
JAMA. 2008;300(4):413-422.
Context Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons, but the incidence and association of CMV reactivation with adverse outcomes in critically ill persons lacking evidence of immunosuppression have not been well defined.
Objective To determine the association of CMV reactivation with intensive care unit (ICU) and hospital length of stay in critically ill immunocompetent persons.
Design, Setting, and Participants We prospectively assessed CMV plasma DNAemia by thrice-weekly real-time polymerase chain reaction (PCR) and clinical outcomes in a cohort of 120 CMV-seropositive, immunocompetent adults admitted to 1 of 6 ICUs at 2 separate hospitals at a large US tertiary care academic medical center between 2004 and 2006. Clinical measurements were assessed by personnel blinded to CMV PCR results. Risk factors for CMV reactivation and association with hospital and ICU length of stay were assessed by multivariable logistic regression and proportional odds models.
Main Outcome Measures Association of CMV reactivation with prolonged hospital length of stay or death.
Results The primary composite end point of continued hospitalization (n = 35) or death (n = 10) by 30 days occurred in 45 (35%) of the 120 patients. Cytomegalovirus viremia at any level occurred in 33% (39/120; 95% confidence interval [CI], 24%-41%) at a median of 12 days (range, 3-57 days) and CMV viremia greater than 1000 copies/mL occurred in 20% (24/120; 95% CI, 13%-28%) at a median of 26 days (range, 9-56 days). By logistic regression, CMV infection at any level (adjusted odds ratio [OR], 4.3; 95% CI, 1.6-11.9; P = .005) and at greater than 1000 copies/mL (adjusted OR, 13.9; 95% CI, 3.2-60; P < .001) and the average CMV area under the curve (AUC) in log10 copies per milliliter (adjusted OR, 2.1; 95% CI, 1.3-3.2; P < .001) were independently associated with hospitalization or death by 30 days. In multivariable partial proportional odds models, both CMV 7-day moving average (OR, 5.1; 95% CI, 2.9-9.1; P < .001) and CMV AUC (OR, 3.2; 95% CI, 2.1-4.7; P < .001) were independently associated with a hospital length of stay of at least 14 days.
Conclusions These preliminary findings suggest that reactivation of CMV occurs frequently in critically ill immunocompetent patients and is associated with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in this setting is warranted.
Author Affiliations: Departments of Laboratory Medicine (Dr Limaye and Ms Santo), Medicine (Drs Limaye, Rubenfeld, Neff, Corey, and Boeckh), Biostatistics (Dr Leisenring), and Surgery (Drs Bulger and Gibran), University of Washington, and the Programs in Infectious Diseases (Drs Huang, Corey, and Boeckh) and Clinical Statistics (Ms Kirby and Dr Leisenring), Fred Hutchinson Cancer Research Center, Seattle.
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