• Ong David S Y DSY Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. , Bonten Marc J M MJM Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. , Cristian Spitoni, Frans M Verduyn Lunel, Jos F Frencken, Janneke Horn, Marcus J Schultz, Tom van der Poll, Klein Klouwenberg Peter M C PMC Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. , Olaf L Cremer, and Molecular Diagnosis and Risk Stratification of Sepsis Consortium.
• Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
• Clin. Infect. Dis. 2017 May 1; 64 (9): 1204-1210.

BackgroundSystemic reactivations of herpesviruses may occur in intensive care unit (ICU) patients, even in those without prior immune deficiency. However, the clinical relevance of these events is uncertain.MethodsIn this study we selected patients admitted with septic shock and treated for more than 4 days from a prospectively enrolled cohort of consecutive adults in the mixed ICUs of 2 tertiary care hospitals in the Netherlands. We excluded patients who had received antiviral treatment in the week before ICU admission and those with known immunodeficiency. We studied viremia episodes with cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), and varicella zoster virus (VZV) by weekly polymerase chain reaction in plasma.ResultsAmong 329 patients, we observed 399 viremia episodes in 223 (68%) patients. Viremia with CMV, EBV, HHV-6, HSV-1, HSV-2, and VZV was detected in 60 (18%), 157 (48%), 80 (24%), 87 (26%), 13 (4%), and 2 (0.6%) patients, respectively; 112 (34%) patients had multiple concurrent viremia events. Crude mortality in the ICU was 36% in this latter group compared to 19% in remaining patients (P < .01). After adjustment for potential confounders, time-dependent bias, and competing risks, only concurrent CMV and EBV reactivations remained independently associated with increased mortality (adjusted subdistribution hazard ratio, 3.17; 95% confidence interval, 1.41-7.13).ConclusionsHerpesvirus reactivations were documented in 68% of septic shock patients without prior immunodeficiency and frequently occurred simultaneously. Concurrent reactivations could be independently associated with mortality.Clinical Trials RegistrationNCT01905033.© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

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