Safety and efficacy of antiviral therapy for prevention of cytomegalovirus reactivation in immunocompetent critically ill patients: A randomized clinical trial

JAMA Internal Medicine

Volumn 177, Issue 6, 2017, Pages 774-783

  Cowley, Nicholas J ^a,b   Owen, Andrew ^a,c   Shiels, Sarah C ^c   Millar, Joanne ^c   Woolley, Rebecca ^a   Ives, Natalie ^a   Osman, Husam ^c   Moss, Paul ^a,c   Bion, Julian F ^a,c  

^a UNIVERSITY OF BIRMINGHAM   (United Kingdom)

^b WORCESTERSHIRE ROYAL HOSPITAL   (United Kingdom)

^c UNIVERSITY HOSPITALS BIRMINGHAM NHS FOUNDATION TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 6; TUMOR NECROSIS FACTOR; VALACICLOVIR; VALGANCICLOVIR; ACICLOVIR; ANTIVIRUS AGENT; VALINE;

ADULT; ALLERGIC REACTION; ANTIVIRAL THERAPY; APACHE; ARTICLE; ARTIFICIAL VENTILATION; BLOOD; BONE MARROW SUPPRESSION; CAUSE OF DEATH; CONTROLLED STUDY; CRITICALLY ILL PATIENT; CYTOMEGALOVIRUS INFECTION; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG WITHDRAWAL; FEMALE; FOLLOW UP; HOSPITAL MORTALITY; HUMAN; INFECTION PREVENTION; INTENSIVE CARE UNIT; LAVAGE FLUID; LOW DRUG DOSE; MAJOR CLINICAL STUDY; MALE; MEDICATION COMPLIANCE; MIDDLE AGED; MORTALITY; NEUTROPENIA; NONDIRECTED BRONCHIOLAR LAVAGE FLUID; OPEN STUDY; OUTCOME ASSESSMENT; PATIENT COMPLIANCE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RASH; RISK FACTOR; SEVERE RENAL IMPAIRMENT; THROAT CULTURE; THROMBOCYTE COUNT; THROMBOCYTE DISORDER; THROMBOCYTOPENIA; TIME; URINE; VIRUS LOAD; VIRUS REACTIVATION; AGED; ANALOGS AND DERIVATIVES; CRITICAL ILLNESS; CYTOMEGALOVIRUS; DRUG ADMINISTRATION; DRUG EFFECT; OPPORTUNISTIC INFECTION; VIROLOGY; VIRUS ACTIVATION; VIRUS INACTIVATION;

ACYCLOVIR; ADULT; AGED; ANTIVIRAL AGENTS; CRITICAL ILLNESS; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; MALE; MIDDLE AGED; OPPORTUNISTIC INFECTIONS; RESPIRATION, ARTIFICIAL; VALACYCLOVIR; VALINE; VIRUS ACTIVATION; VIRUS INACTIVATION;

EID: 85020708598     PISSN: 21686106     EISSN: None     Source Type: Journal    
DOI: 10.1001/jamainternmed.2017.0895     Document Type: Article

References (46)

1. Tookey PA, Ades AE, Peckham CS. Cytomegalovirus prevalencein pregnant women: the influence of parity. Arch Dis Child. 1992;67(7 Spec No):779-783.
2. Bate SL, Dollard SC, Cannon MJ. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis. 2010;50(11):1439-1447.
3. Staras SA, Dollard SC, Radford KW, Flanders WD, Pass RF, Cannon MJ. Seroprevalence of cytomegalovirus infection in the United States, 1988-1994. Clin Infect Dis. 2006;43(9):1143-1151.
4. Yahav D, Gafter-Gvili A, Muchtar E, et al. Antiviral prophylaxis in haematological patients: systematic review and meta-analysis. Eur J Cancer. 2009;45(18):3131-3148.
5. Hodson EM, Craig JC, Strippoli GF, Webster AC. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2008;(2): CD003774.
6. Kalil AC, Levitsky J, Lyden E, Stoner J, Freifeld AG. Meta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipients. Ann Intern Med. 2005; 143(12):870-880.
7. Preiksaitis JK, Brennan DC, Fishman J, Allen U. Canadian Society of Transplantation consensus workshopon cytomegalovirus managementin solid organ transplantation final report. Am J Transplant. 2005;5(2):218-227.
8. Puius YA, Snydman DR. Prophylaxis and treatment of cytomegalovirus disease in recipients of solid organ transplants: current approach and future challenges. Curr Opin Infect Dis. 2007;20(4): 419-424.
9. Limaye AP, Kirby KA, Rubenfeld GD, et al. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA. 2008;300(4): 413-422.
10. Heininger A, Jahn G, Engel C, Notheisen T, Unertl K, Hamprecht K. Human cytomegalovirus infections in nonimmunosuppressed critically ill patients. Crit Care Med. 2001;29(3):541-547.
11. Cook CH, Martin LC, Yenchar JK, et al. Occult herpes family viral infections are endemic in critically ill surgical patients. Crit Care Med. 2003;31 (7):1923-1929.
12. von Müller L, Klemm A, Weiss M, et al. Active cytomegalovirus infection in patients with septic shock. Emerg Infect Dis. 2006;12(10):1517-1522.
13. Ziemann M, Sedemund-Adib B, Reiland P, Schmucker P, Hennig H. Increased mortality in long-term intensive care patients with active cytomegalovirus infection. Crit Care Med. 2008;36 (12):3145-3150.
14. Chiche L, Forel J-M, Roch A, et al. Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients. Crit Care Med. 2009;37(6):1850-1857.
15. Jaber S, Chanques G, Borry J, et al. Cytomegalovirus infection in critically ill patients: associated factors and consequences. Chest. 2005; 127(1):233-241.
16. Papazian L, Fraisse A, Garbe L, et al. Cytomegalovirus:an unexpected cause of ventilator-associated pneumonia. Anesthesiology. 1996;84(2):280-287.
17. Domart Y, Trouillet JL, Fagon JY, Chastre J, Brun-Vezinet F, Gibert C. Incidence and morbidity of cytomegaloviral infection in patients with mediastinitis following cardiac surgery. Chest. 1990; 97(1):18-22.
18. Coisel Y, Bousbia S, Forel JM, et al. Cytomegalovirus and herpes simplex virus effect on the prognosis of mechanically ventilated patients suspected to have ventilator-associated pneumonia. PLoS One. 2012;7(12):e51340.
19. Stéphan F, Méharzi D, Ricci S, Fajac A, Clergue F, Bernaudin JF. Evaluation by polymerase chain reaction of cytomegalovirus reactivation in intensive care patients under mechanical ventilation. Intensive Care Med. 1996;22(11): 1244-1249.
20. Kutza AS, Muhl E, Hackstein H, Kirchner H, Bein G. High incidence of active cytomegalovirus infection among septic patients. Clin Infect Dis. 1998;26(5):1076-1082.
21. Desachy A, Ranger-Rogez S, François B, et al. Reactivation of human herpesvirus type 6 in multiple organ failure syndrome. Clin Infect Dis. 2001;32(2):197-203.
22. Razonable RR, Fanning C, Brown RA, et al. Selective reactivation of human herpesvirus 6 variant A occurs in critically ill immunocompetent hosts. J Infect Dis. 2002;185(1):110-113.
23. Kalil AC, Florescu DF. Prevalence and mortality associated with cytomegalovirus infection in nonimmunosuppressed patients in the intensive care unit. Crit Care Med. 2009;37(8):2350-2358.
24. Prösch S, Wendt CE, Reinke P, et al. A novel link between stress and human cytomegalovirus (HCMV) infection: sympathetic hyperactivity stimulates HCMV activation. Virology. 2000;272 (2):357-365.
25. Cook CH, Zhang Y, Sedmak DD, Martin LC, Jewell S, Ferguson RM. Pulmonary cytomegalovirus reactivation causes pathology in immunocompetent mice. Crit Care Med. 2006;34(3):842-849.
26. Cook CH, Trgovcich J, Zimmerman PD, Zhang Y, Sedmak DD. Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1β triggers reactivation of latent cytomegalovirus inimmunocompetent mice. J Virol. 2006;80(18):9151-9158.
27. Tanaka S, Toh Y, Minagawa H, Mori R, Sugimachi K, Minamishima Y. Reactivation of cytomegalovirus in patients with cirrhosis: analysis of 122 cases. Hepatology. 1992;16(6):1409-1414.
28. Ho M. Cytomegalovirus infection in patients with bacterial sepsis. Clin Infect Dis. 1998;26(5): 1083-1084.
29. Smith PD, Saini SS, Raffeld M, Manischewitz JF, Wahl SM. Cytomegalovirus inductionoftumor necrosis factor-alpha byhuman monocytes and mucosal macrophages. J Clin Invest. 1992;90(5): 1642-1648.
30. Andrews DM, Andoniou CE, Granucci F, Ricciardi-Castagnoli P, Degli-Esposti MA. Infection of dendritic cells by murine cytomegalovirus induces functional paralysis. Nat Immunol. 2001;2 (11):1077-1084.
31. Freeman RB Jr. The 'indirect' effects of cytomegalovirus infection. Am J Transplant. 2009; 9(11):2453-2458.
32. Osawa R, Singh N. Cytomegalovirus infection in critically ill patients: a systematic review. Crit Care. 2009;13(3):R68.
33. Forster MR, Trgovcich J, Zimmerman P, et al. Antiviral prevention of sepsis induced cytomegalovirus reactivation inimmunocompetent mice. Antiviral Res. 2010;85(3):496-503.
34. Kalil AC, Mindru C, Florescu DF. Effectiveness of valganciclovir 900 mgversus 450mg for cytomegalovirus prophylaxis in transplantation: direct and indirect treatment comparison meta-analysis. Clin Infect Dis. 2011;52(3):313-321.
35. Vincent JL, Moreno R, Takala J, et al. The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure: on behalf of the Working Groupon Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med. 1996;22(7):707-710.
36. Ferreira FL, Bota DP, Bross A, Mélot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA. 2001;286 (14):1754-1758.
37. Chase JG, Pretty CG, Pfeifer L, et al. Organ failure and tight glycemic control in the SPRINT study. Crit Care. 2010;14(4):R154.
38. Vincent JL, de Mendonça A, Cantraine F, et al. Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study: working group on 'sepsis-related problems' of the European Society of Intensive Care Medicine. Crit Care Med. 1998;26(11):1793-1800.
39. Sedý JR, Spear PG, Ware CF. Cross-regulation between herpesviruses and the TNF superfamily members. Nat Rev Immunol. 2008;8(11):861-873.
40. Roberts ET, Haan MN, Dowd JB, Aiello AE. Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol. 2010;172(4):363-371.
41. Griffith DM, Lewis S, Rossi AG, et al; RECOVER Investigators. Systemic inflammation after critical illness: relationship with physical recovery and exploration of potential mechanisms. Thorax. 2016; 71(9):820-829.
42. Lowance D, Neumayer HH, Legendre CM, et al; International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study Group. Valacyclovir for the prevention of cytomegalovirus disease after renal transplantation. N Engl J Med. 1999;340(19):1462-1470.
43. Reischig T, Jindra P, Hes O, Svecová M, Klaboch J, Treska V. Valacyclovir prophylaxis versus preemptive valganciclovir therapy to prevent cytomegalovirus disease after renal transplantation. Am J Transplant. 2008;8(1):69-77.
44. Winston DJ, Yeager AM, Chandrasekar PH, Snydman DR, Petersen FB, Territo MC; Valacyclovir Cytomegalovirus Study Group. Randomized comparison of oral valacyclovir and intravenous ganciclovir for prevention of cytomegalovirus disease after allogeneic bone marrow transplantation. Clin Infect Dis. 2003;36(6):749-758.
45. Reinke P, Prösch S, Kern F, Volk HD. Mechanismsofhumancytomegalovirus (HCMV) (re)activation and its impact on organ transplant patients. Transpl Infect Dis. 1999;1(3):157-164.
46. Ruell J, Barnes C, Mutton K, et al. Active CMV disease does not always correlate with viral load detection. Bone Marrow Transplant. 2007;40(1): 55-61.