Cytomegalovirus reactivation in critically ill immunocompetent patients

Abstract

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.

Figure 1

Figure 1A. Cumulative incidence of CMV viremia at any level stratified by ICU Figure 1B. Cumulative incidence of CMV viremia at >1,000 copies/ml stratified by ICU Figure 1C. Cumulative incidence (and 95% confidence intervals) of CMV viremia at any level or >1,000 copies/ml (all patients, n=120)

Figure 1

Figure 1A. Cumulative incidence of CMV viremia at any level stratified by ICU Figure 1B. Cumulative incidence of CMV viremia at >1,000 copies/ml stratified by ICU Figure 1C. Cumulative incidence (and 95% confidence intervals) of CMV viremia at any level or >1,000 copies/ml (all patients, n=120)

Figure 1

Figure 1A. Cumulative incidence of CMV viremia at any level stratified by ICU Figure 1B. Cumulative incidence of CMV viremia at >1,000 copies/ml stratified by ICU Figure 1C. Cumulative incidence (and 95% confidence intervals) of CMV viremia at any level or >1,000 copies/ml (all patients, n=120)

Figure 2. Predicted probability of death or continued hospitalization by day 30 as a function of average CMV AUC, adjusted for unit and baseline ventilator use

Note: The predicted probabilities of death or continued hospitalization were estimated from a logistic regression model of average CMV AUC adjusted for unit and baseline ventilator use.

Figure 3. Cumulative incidence (with 95% confidence intervals) of discharge from hospital after 30 days according to CMV reactivation status

Note: Figure 3 shows probability of discharge after day 30 among 35 patients still hospitalized by day 30. Patients were categorized as CMV reactivators if they tested positive by PCR prior to day 30. Log-rank test p-value=0.03.