title: Cytomegalovirus reactivation in critically ill immunocompetent patients.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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 log(10) 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.
authors.affiliation: Department of Laboratory Medicine, University of Washington Medical Center, 1959 NE Pacific St, Seattle, WA 98195-7110, USA. limaye@u.washington.edu
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Limaye
authors.forename: Katharine A
authors.initials: KA
authors.lastname: Kirby
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Rubenfeld
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Leisenring
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Bulger
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Neff
authors.forename: Nicole S
authors.initials: NS
authors.lastname: Gibran
authors.forename: Meei-Li
authors.initials: ML
authors.lastname: Huang
authors.forename: Tracy K
authors.initials: TK
authors.lastname: Santo Hayes
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: Michael
authors.initials: M
authors.lastname: Boeckh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016638:Critical Illness / Q000401:mortality; D003587:Cytomegalovirus / Q000302:isolation & purification / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D005260:Female; D006801:Humans; D007121:Immunocompetence / Q000276:immunology; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D019562:Viral Load; D014766:Viremia; D014775:Virus Activation