Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis

Abstract

IntroductionSepsis has been identified as a risk factor for human cytomegalovirus (CMV) reactivation in critically ill patients. However, the contribution of CMV reactivation on morbidity and mortality is still controversial. Therefore, we analyzed the incidence and impact of CMV reactivation on outcome in patients with severe sepsis.MethodsIn a prospective longitudinal double-blinded observational study, 97 adult nonimmunosuppressed CMV-seropositive patients with new onset of severe sepsis were included. Leukocytes, plasma and tracheal secretions were examined weekly for CMV-DNA by PCR. Tracheal secretions were additionally tested for HSV (Herpes Simplex Virus)-DNA. The influence of CMV-reactivation on the endpoints was analysed by Cox proportional-hazard regression analysis. Time-dependency was evaluated by landmark analysis.ResultsSix out 97 died and five were discharged from the hospital within 72 hours and were excluded of the analysis. CMV reactivation occurred in 35 of the 86 (40.69%) analysed patients. HSV infection occurred in 23 of the 35 (65.7%) CMV reactivators. In 10 patients CMV-plasma-DNAemia appeared with a DNA-content below 600 copies/ml in four cases and a peak amount of 2,830 copies/ml on average. In patients with and without CMV reactivation mortality rates were similar (37.1% vs. 35.3%, P = 0.861), respectively. However, in the multivariate COX regression analyses CMV reactivation was independently associated with increased length of stay in the ICU (30.0, interquartile range 14 to 48 vs. 12.0, interquartile range 7 to 19 days; HR (hazard ratio) 3.365; 95% CI (confidence interval) 1.233 to 9.183, P = 0.018) and in the hospital (33.0, interquartile range 24 to 62 vs. 16.0, interquartile range 10 to 24 days, HR 3.3, 95% CI 1.78 to 6.25, P < 0.001) as well as prolonged mechanical ventilation (22.0, interquartile range 6 to 36 vs. 7.5, interquartile range 5 to 15.5 days; HR 2.6,CI 95% 1.39 to 4.94; P < 0.001) and impaired pulmonary gas exchange (six days, interquartile range 1 to 17, vs. three, interquartile range 1 to 7, days in reactivators vs. non-reactivators, P = 0.038). HSV reactivation proved not to be a risk factor for these adverse effects.ConclusionsThese data indicate an independent correlation between CMV reactivation and increased morbidity in the well-defined group of nonimmunosuppressed patients with severe sepsis, but CMV reactivation had no impact on mortality in this group with low CMV-DNA plasma levels. Thus, the potential harms and benefits of antiviral treatment have to be weighed cautiously in patients with severe sepsis or septic shock.

Active Cytomegalovirus Infection in Critically Ill Immunocompeten Patients Admitted in the ICU. A Molecular Diagnosis Approach

“…However, this result similar to previously published datas from other researchers [32% (Muller, 2006), 33% (Limaye, 2008) and 40.69% (Heininger, 2011)]. 2,9,16 The variability of those data might be caused by: (1) 16 In this research, the disease severity had a weak correlation with the occurrence of active CMV infection. It could be caused by time gap in examining those two variables.…”

IL-7 Restores Lymphocyte Functions in Septic Patients

“…These lymphocyte dysfunctions are likely illustrated in patients by viral reactivations normally solely occurring in immunocompromised hosts (CMV and herpes simplex virus). Importantly, they are associated with deleterious outcome after septic shock (22,23). Therefore immunostimulating therapies able to restore these lymphocyte dysfunctions would represent an innovative therapeutic strategy in septic shock.…”

Changes in intensive care for allogeneic hematopoietic stem cell transplant recipients

“…Moreover, it is a surrogate for the underlying immunosuppression and has consistently been reported to affect outcomes of allogeneic HSCT recipients, as well as of all ICU patients with immunosuppression-related acute illnesses. 36,37 Finally, invasive aspergillosis is not associated with impaired outcomes presumably owing to the widespread use of active antifungal therapies, whereas other invasive fungal infections still remain of adverse prognostic significance. 38 A possible explanation for the improved survival in our recent cohort is ICU admission at an earlier phase of organ dysfunction.…”