Exclusion criteria were the following: age younger than 18 years, pregnancy or breast feeding, duration of severe sepsis selleck screening library for longer than 72 hours, antiviral treatment with ganciclovir, valaciclovir, cidofovir, or foscarnet in the previous 7 days, and manifest immunosuppression because of HIV infection, congenital defects, leukopenia <2,000/��l, radiation or treatment with immunosuppressive substances within the last 6 months including prednisone, rituximab, alemtuzumab, tacrolimus, sirolimus, ciclosporin, mycophenolic acid, azathioprine, anti-lymphocytic or anti-IL6 antibodies.Study protocolThe investigation was approved by the local ethics committee of the Faculty of Medicine, which waived the need for informed consent.

As soon as a patient fulfilled the inclusion criterion of severe sepsis and had no exclusion criterion present the first set of virological examinations including CMV serology was performed within the next three days.Patients having a positive anti-CMV IgG titer were enrolled and further monitored for CMV reactivation once a week until discharge from the University Hospital or death.Clinicians were not aware of the virological results, since they were assessed in a specific internal database applied for scientific purposes only. Ordering examinations to look for CMV disease as well as the initiation of antiviral treatment was left to the decision of the clinician, independently of the study.

The following data were evaluated at enrolment: age, gender, underlying disease requiring ICU treatment, the type of infection and the organ dysfunction constituting severe sepsis, presence of septic shock, the length of stay in the ICU, duration of mechanical ventilation and severity of illness and organ dysfunction as indicated by the Simplified Acute Physiology Score (SAPS) II [20] and the Sequential Organ Failure Assessment (SOFA) scores. Additionally, the records of each patient were reviewed for the presence of malignant disease, the number of surgical procedures, and the number of red blood cell units transfused during the current hospital stay before enrolment. After enrolment it was registered whether a CMV disease was diagnosed by the responsible clinicians. The study nurses collecting clinical data were blinded for virological findings with the exception of CMV serology, which was reported immediately.

The consequences of active CMV infection were longitudinally examined from enrolment until discharge or death by assessing in-hospital mortality, length of stay (LOS) in the ICU and in the hospital as well as time on mechanical ventilator.Virological assaysSamples were processed in the virological laboratory each Monday and Thursday independently from the day severe sepsis Anacetrapib was diagnosed. The personnel performing the virological examinations had no contact with patients and no insight into clinical data. All data were fed into an internal database for scientific purposes to ensure mutual blinding.