Epidemiology of Multiple Herpes Viremia in Previously Immunocompetent Patients With Septic Shock.
Systemic 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.



In 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.



Among 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).



Herpesvirus reactivations were documented in 68% of septic shock patients without prior immunodeficiency and frequently occurred simultaneously. Concurrent reactivations could be independently associated with mortality.



NCT01905033.
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
David S Y
DSY
Ong
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Marc J M
MJM
Bonten
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Mathematics, Utrecht University, The Netherlands.
Cristian
C
Spitoni
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Frans M
FM
Verduyn Lunel
Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
Jos F
JF
Frencken
Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands.
Janneke
J
Horn
Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands.
Marcus J
MJ
Schultz
Division of Infectious Diseases & Center of Experimental and Molecular Medicine Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, The Netherlands.
Tom
T
van der Poll
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.|Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Peter M C
PMC
Klein Klouwenberg
Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Olaf L
OL
Cremer
D000368:Aged; D005260:Female; D006564:Herpesviridae / Q000145:classification / Q000302:isolation & purification*; D006566:Herpesviridae Infections / Q000150:complications / Q000453:epidemiology* / Q000821:virology; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D011446:Prospective Studies; D012772:Shock, Septic / Q000453:epidemiology* / Q000209:etiology*; D062606:Tertiary Care Centers; D014766:Viremia / Q000150:complications / Q000453:epidemiology* / Q000821:virology
Epstein–Barr virus; cytomegalovirus; human herpesvirus 6; reactivation; mortality