Cytomegalovirus reactivation and associated outcome of critically ill patients with severe sepsis
1 Klinik für Anaesthesiologie und Intensivmedizin, University Hospital of Tübingen, Hoppe-Seyler-Str.03, 72076 Tübingen, Germany
2 Biostatistik-Tübingen, Burgunderweg 36, 72070 Tübingen, Germany
3 Institut für Medizinische Biometrie, Westbahnhofstr. 55, 72070 Tübingen, Germany
4 Institut für Medizinische Virologie und Epidemiologie der Viruskrankheiten, University Hospital of Tübingen, Elfriede-Aulhorn-Str. 6, 72076 Tübingen, Germany
5 Klinik für Innere Medizin, University Hospital of Tübingen, Otfried-Müller-Straße 10, 72076 Tübingen, Germany
6 Inzlingerstr.3, 79639 Grenzach-Wyhlen, Germany
7 Universitätsklinik für Allgemeine, Viszeral- und Transplantationschirurgie, University Hospital of Tübingen, Hoppe-Seyler-Str.03, 72076 Tübingen, Germany
Critical Care 2011, 15:R77 doi:10.1186/cc10069
See related commentary by Kalil and Florescu, http://ccforum.com/content/15/2/138Published: 1 March 2011
Sepsis 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.
In 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.
Six 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.
These 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.