JAMA. 2008 Jul 23;300(4):413-22.
Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, Gibran NS,
Huang ML, Santo Hayes TK, Corey L, Boeckh M.
Department of Laboratory Medicine, University of Washington Medical Center, 1959
NE Pacific St, Seattle, WA 98195-7110, USA. limaye@u.washington.edu
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
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.