Association Between Cytomegalovirus Reactivation and Clinical Outcomes in Immunocompetent Critically Ill Patients: A Systematic Review and Meta-Analysis

Background. The aim of our systematic review was to investigate the association between cytomegalovirus (CMV) reactivation and outcomes in immunocompetent critically ill patients. Methods. We searched electronic databases and gray literature for original studies and abstracts published between 1990 and October 2016. The review was limited to studies including critically ill immunocompetent patients. Cytomegalovirus reactivation was defined as positive polymerase chain reaction, pp65 antigenemia, or viral culture from blood or bronchoalveolar lavage. Selected patient-centered outcomes included mortality, duration of mechanical ventilation, need for renal replacement therapy (RRT), and nosocomial infections. Health resource utilization outcomes included intensive care unit and hospital lengths of stay. Results. Twenty-two studies were included. In our primary analysis, CMV reactivation was associated with increased ICU mortality (odds ratio [OR], 2.55; 95% confidence interval [CI], 1.87-3.47), overall mortality (OR, 2.02; 95% CI, 1.60-2.56), duration of mechanical ventilation (mean difference 6.60 days; 95% CI, 3.09-10.12), nosocomial infections (OR, 3.20; 95% CI, 2.05-4.98), need for RRT (OR, 2.37; 95% CI, 1.31-4.31), and ICU length of stay (mean difference 8.18 days; 95% CI, 6.14-10.22). In addition, numerous sensitivity analyses were performed. Conclusions. In this meta-analysis, CMV reactivation was associated with worse clinical outcomes and greater health resource utilization in critically ill patients. However, it remains unclear whether CMV reactivation plays a causal role or if it is a surrogate for more severe illness.