Cytomegalovirus infection in critically ill patients: a systematic review

Ryosuke Osawa, Nina Singh, Ryosuke Osawa, Nina Singh

Abstract

Introduction: The precise role of cytomegalovirus (CMV) infection in contributing to outcomes in critically ill immunocompetent patients has not been fully defined.

Methods: Studies in which critically ill immunocompetent adults were monitored for CMV infection in the intensive care unit (ICU) were reviewed.

Results: CMV infection occurs in 0 to 36% of critically ill patients, mostly between 4 and 12 days after ICU admission. Potential risk factors for CMV infection include sepsis, requirement of mechanical ventilation, and transfusions. Prolonged mechanical ventilation (21 to 39 days vs. 13 to 24 days) and duration of ICU stay (33 to 69 days vs. 22 to 48 days) correlated significantly with a higher risk of CMV infection. Mortality rates in patients with CMV infection were higher in some but not all studies. Whether CMV produces febrile syndrome or end-organ disease directly in these patients is not known.

Conclusions: CMV infection frequently occurs in critically ill immunocompetent patients and may be associated with poor outcomes. Further studies are warranted to identify subsets of patients who are likely to develop CMV infection and to determine the impact of antiviral agents on clinically meaningful outcomes in these patients.

References

    1. Staras SAS, 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. doi: 10.1086/508173.
    1. Kuppermann BD, Petty JG, Richman DD, Mathews WC, Fullerton SC, Rickman LS, Freeman WR. Correlation between CD4+ counts and prevalence of cytomegalovirus retinitis and human immunodeficiency virus-related noninfectious retinal vasculopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol. 1993;115(5):575–582.
    1. Hodson EM, Craig JC, Strippoli GFM, Webster AC. Antiviral medications for preventing cytomegalovirus disease in solid organ transplant recipients. Cochrane Database Syst Rev. 2008;(2):CD003774.
    1. 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.
    1. Small LN, Lau J, Snydman DR. Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapies. Clin Infect Dis. 2006;43(7):869–880. doi: 10.1086/507337.
    1. Döcke WD, Prösch S, Fietze E, Kimel V, Zuckermann H, Klug C, Syrbe U, Krüger DH, von Baehr R, Volk HD. Cytomegalovirus reactivation and tumour necrosis factor. Lancet. 1994;343(8892):268–269. doi: 10.1016/S0140-6736(94)91116-9.
    1. 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. doi: 10.1086/520307.
    1. Cook CH, Martin LC, Yenchar JK, Lahm MC, McGuinness B, Davies EA, Ferguson RM. Occult herpes family viral infections are endemic in critically ill surgical patients. Crit Care Med. 2003;31(7):1923–1929. doi: 10.1097/01.CCM.0000070222.11325.C4.
    1. 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. doi: 10.1097/CCM.0b013e31818f3fc4.
    1. 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. doi: 10.1097/00003246-200103000-00012.
    1. Limaye AP, Kirby KA, Rubenfeld GD, Leisenring WM, Bulger EM, Neff MJ, Gibran NS, Huang M-L, Santo Hayes TK, Corey L, Boeckh M. Cytomegalovirus reactivation in critically ill immunocompetent patients. JAMA. 2008;300(4):413–422. doi: 10.1001/jama.300.4.413.
    1. Desachy A, Ranger-Rogez S, François B, Venot C, Traccard I, Gastinne H, Denis F, Vignon P. Reactivation of human herpesvirus type 6 in multiple organ failure syndrome. Clin Infect Dis. 2001;32(2):197–203. doi: 10.1086/318474.
    1. 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. doi: 10.1378/chest.97.1.18.
    1. 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. doi: 10.1007/BF01709343.
    1. Razonable RR, Fanning C, Brown RA, Espy MJ, Rivero A, Wilson J, Kremers W, Smith TF, Paya CV. Selective reactivation of human herpesvirus 6 variant A occurs in critically ill immunocompetent hosts. J Infect Dis. 2002;185(1):110–113. doi: 10.1086/324772.
    1. von Müller L, Klemm A, Weiss M, Schneider M, Suger-Wiedeck H, Durmus N, Hampl W, Mertens T. Active cytomegalovirus infection in patients with septic shock. Emerg Infect Dis. 2006;12(10):1517–1522.
    1. Cook CH, Yenchar JK, Kraner TO, Davies EA, Ferguson RM. Occult herpes family viruses may increase mortality in critically ill surgical patients. Am J Surg. 1998;176(4):357–360. doi: 10.1016/S0002-9610(98)00205-0.
    1. Jaber S, Chanques G, Borry J, Souche B, Verdier R, Perrigault P-F, Eledjam J-J. Cytomegalovirus infection in critically ill patients: associated factors and consequences. Chest. 2005;127(1):233–241. doi: 10.1378/chest.127.1.233.
    1. Bale JF, Kealey GP, Massanari RM, Strauss RG. The epidemiology of cytomegalovirus infection among patients with burns. Infect Control Hosp Epidemiol. 1990;11(1):17–22.
    1. Curtsinger LJ, Cheadle WG, Hershman MJ, Cost K, Polk HC., Jr Association of cytomegalovirus infection with increased morbidity is independent of transfusion. Am J Surg. 1989;158(6):606–610. doi: 10.1016/0002-9610(89)90204-3. discussion 610–601.
    1. Kagan RJ, Naraqi S, Matsuda T, Jonasson OM. Herpes simplex virus and cytomegalovirus infections in burned patients. J Trauma. 1985;25(1):40–45. doi: 10.1097/00005373-198501000-00007.
    1. Kealey GP, Bale JF, Strauss RG, Massanari RM. Cytomegalovirus infection in burn patients. J Burn Care Rehabil. 1987;8(6):543–545. doi: 10.1097/00004630-198708060-00017.
    1. Moran KT, Thupari JN, O'Reilly TJ, Munster AM. Effect of immunoglobulin G therapy on serum antibody titers to cytomegalovirus in burn patients. Am J Surg. 1988;155(2):294–297. doi: 10.1016/S0002-9610(88)80718-9.
    1. Seeman J, Konigová R. Cytomegalovirus infection in severely burned patients. Acta Chir Plast. 1976;18(3):142–151.
    1. Matthews SCW, Levick PL, Coombes EJ, Ely DW, Pead PJ, Saeed AA. Viral infections in a group of burned patients. Burns. 1979;6(1):55–60. doi: 10.1016/0305-4179(79)90040-8.
    1. Knockaert DC, Bruel AA Van den, Goubau PF, Bobbaers HJ. Cytomegalovirus infection in immunocompetent adults. Eur J Med. 1992;1(7):434–436.
    1. Wiener-Well Y, Yinnon AM, Singer P, Hersch M. Reactivation of cytomegalovirus in critically sick patients. Isr Med Assoc J. 2006;8(8):583–584.
    1. von Müller L, Klemm A, Durmus N, Weiss M, Suger-Wiedeck H, Schneider M, Hampl W, Mertens T. Cellular immunity and active human cytomegalovirus infection in patients with septic shock. J Infect Dis. 2007;196(9):1288–1295. doi: 10.1086/522429.
    1. Papazian L, Doddoli C, Chetaille B, Gernez Y, Thirion X, Roch A, Donati Y, Bonnety M, Zandotti C, Thomas P. A contributive result of open-lung biopsy improves survival in acute respiratory distress syndrome patients. Crit Care Med. 2007;35(3):755–762. doi: 10.1097/01.CCM.0000257325.88144.30.
    1. Papazian L, Thomas P, Bregeon F, Garbe L, Zandotti C, Saux P, Gaillat F, Drancourt M, Auffray JP, Gouin F. Open-lung biopsy in patients with acute respiratory distress syndrome. Anesthesiology. 1998;88(4):935–944. doi: 10.1097/00000542-199804000-00013.
    1. Papazian L, Fraisse A, Garbe L, Zandotti C, Thomas P, Saux P, Pierrin G, Gouin F. Cytomegalovirus. An unexpected cause of ventilator-associated pneumonia. Anesthesiology. 1996;84(2):280–287. doi: 10.1097/00000542-199602000-00005.
    1. Boeckh M, Boivin G. Quantitation of cytomegalovirus: methodologic aspects and clinical applications. Clin Microbiol Rev. 1998;11(3):533–554.
    1. Drew WL. Laboratory diagnosis of cytomegalovirus infection and disease in immunocompromised patients. Curr Opin Infect Dis. 2007;20(4):408–411. doi: 10.1097/QCO.0b013e32821f6010.
    1. Dockrell DH, Prada J, Jones MF, Patel R, Badley AD, Harmsen WS, Ilstrup DM, Wiesner RH, Krom RA, Smith TF, Paya CV. Seroconversion to human herpesvirus 6 following liver transplantation is a marker of cytomegalovirus disease. J Infect Dis. 1997;176(5):1135–1140. doi: 10.1086/514104.
    1. Kidd IM, Clark DA, Sabin CA, Andrew D, Hassan-Walker AF, Sweny P, Griffiths PD, Emery VC. Prospective study of human betaherpesviruses after renal transplantation: association of human herpesvirus 7 and cytomegalovirus co-infection with cytomegalovirus disease and increased rejection. Transplantation. 2000;69(11):2400–2404. doi: 10.1097/00007890-200006150-00032.
    1. Osman HK, Peiris JS, Taylor CE, Warwicker P, Jarrett RF, Madeley CR. "Cytomegalovirus disease" in renal allograft recipients: is human herpesvirus 7 a co-factor for disease progression? J Med Virol. 1996;48(4):295–301. doi: 10.1002/(SICI)1096-9071(199604)48:4<295::AID-JMV1>;2-2.
    1. Singh N. Interactions between viruses in transplant recipients. Clin Infect Dis. 2005;40(3):430–436. doi: 10.1086/427214.
    1. Emery VC. Human herpesviruses 6 and 7 in solid organ transplant recipients. Clin Infect Dis. 2001;32(9):1357–1360. doi: 10.1086/320000.
    1. Griffiths PD, Ait-Khaled M, Bearcroft CP, Clark DA, Quaglia A, Davies SE, Burroughs AK, Rolles K, Kidd IM, Knight SN, Noibi SM, Cope AV, Phillips AN, Emery VC. Human herpesviruses 6 and 7 as potential pathogens after liver transplant: prospective comparison with the effect of cytomegalovirus. J Med Virol. 1999;59(4):496–501. doi: 10.1002/(SICI)1096-9071(199912)59:4<496::AID-JMV12>;2-U.
    1. Singh N. Human herpesviruses-6, -7 and -8 in organ transplant recipients. Clin Microbiol Infect. 2000;6(9):453–459. doi: 10.1046/j.1469-0691.2000.00129.x.
    1. Cook CH, Zhang Y, McGuinness BJ, Lahm MC, Sedmak DD, Ferguson RM. Intra-abdominal bacterial infection reactivates latent pulmonary cytomegalovirus in immunocompetent mice. J Infect Dis. 2002;185(10):1395–1400. doi: 10.1086/340508.
    1. 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.
    1. Cook CH, Trgovcich J, Zimmerman PD, Zhang Y, Sedmak DD. Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1beta triggers reactivation of latent cytomegalovirus in immunocompetent mice. J Virol. 2006;80(18):9151–9158. doi: 10.1128/JVI.00216-06.
    1. Hummel M, Abecassis MM. A model for reactivation of CMV from latency. J Clin Virol. 2002;25(Suppl 2):S123–136. doi: 10.1016/S1386-6532(02)00088-4.
    1. Bone RC. Sir Isaac Newton, sepsis, SIRS, and CARS. Crit Care Med. 1996;24(7):1125–1128. doi: 10.1097/00003246-199607000-00010.
    1. Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med. 2003;348(2):138–150. doi: 10.1056/NEJMra021333.
    1. Zedtwitz-Liebenstein K, Jaksch P, Wulkersdorfer B, Friehs H, Pempelfort SD, Burgmann H, Frass M. Usefulness of interleukin-10 detection in lung transplant patients with human cytomegalovirus infection with respect to virus persistence. Transplantation. 2007;84(2):268–271. doi: 10.1097/01.tp.0000267157.78945.9d.
    1. Gogos CA, Drosou E, Bassaris HP, Skoutelis A. Pro- versus anti-inflammatory cytokine profile in patients with severe sepsis: a marker for prognosis and future therapeutic options. J Infect Dis. 2000;181(1):176–180. doi: 10.1086/315214.
    1. Vamvakas EC, Blajchman MA. Transfusion-related immunomodulation (TRIM): an update. Blood Rev. 2007;21(6):327–348. doi: 10.1016/j.blre.2007.07.003.
    1. Opelz G, Sengar DP, Mickey MR, Terasaki PI. Effect of blood transfusions on subsequent kidney transplants. Transplant Proc. 1973;5(1):253–259.
    1. Amato A, Pescatori M. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane Database Syst Rev. 2006;(1):CD005033.
    1. Hill GE, Frawley WH, Griffith KE, Forestner JE, Minei JP. Allogeneic blood transfusion increases the risk of postoperative bacterial infection: a meta-analysis. J Trauma. 2003;54(5):908–914. doi: 10.1097/01.TA.0000022460.21283.53.
    1. Bowden RA, Slichter SJ, Sayers M, Weisdorf D, Cays M, Schoch G, Banaji M, Haake R, Welk K, Fisher L, McCullough J, Miller W. A comparison of filtered leukocyte-reduced and cytomegalovirus (CMV) seronegative blood products for the prevention of transfusion-associated CMV infection after marrow transplant. Blood. 1995;86(9):3598–3603.
    1. Nichols WG, Price TH, Gooley T, Corey L, Boeckh M. Transfusion-transmitted cytomegalovirus infection after receipt of leukoreduced blood products. Blood. 2003;101(10):4195–4200. doi: 10.1182/blood-2002-10-3143.
    1. Hayden FG, Himel HN, Heggers JP. Herpesvirus infections in burn patients. Chest. 1994;106(1 Suppl):15S–21S. discussion 34S-35S.
    1. Rennekampff H-O, Hamprecht K. Cytomegalovirus infection in burns: a review. J Med Microbiol. 2006;55(Pt 5):483–487. doi: 10.1099/jmm.0.46079-0.
    1. Miller AC, Rashid RM, Elamin EM. The "T" in trauma: the helper T-cell response and the role of immunomodulation in trauma and burn patients. J Trauma. 2007;63(6):1407–1417. doi: 10.1097/TA.0b013e31815b839e.
    1. Murphy TJ, Ni Choileain N, Zang Y, Mannick JA, Lederer JA. CD4+CD25+ regulatory T cells control innate immune reactivity after injury. J Immunol. 2005;174(5):2957–2963.
    1. Cairns BA, Maile R, Buchanan I, Pilati D, DeSerres S, Collins EJ, Frelinger JA, Meyer AA. CD8(+) T cells express a T-helper 1–like phenotype after burn injury. Surgery. 2001;130(2):210–216. doi: 10.1067/msy.2001.115835.
    1. Bonnet F, Neau D, Viallard JF, Morlat P, Ragnaud JM, Dupon M, Legendre P, Imbert Y, Lifermann F, Le Bras M, Beylot J, Longy-Boursier M. Clinical and laboratory findings of cytomegalovirus infection in 115 hospitalized non-immunocompromised adults. Ann Med Interne (Paris) 2001;152(4):227–235.
    1. Wreghitt TG, Teare EL, Sule O, Devi R, Rice P. Cytomegalovirus infection in immunocompetent patients. Clin Infect Dis. 2003;37(12):1603–1606. doi: 10.1086/379711.
    1. Cacopardo B, Nigro L. Clinical features of cytomegalic disease in immunocompetent subjects: a 1990–2000 survey. Ann Ital Med Int. 2003;18(2):83–88.
    1. Eddleston M, Peacock S, Juniper M, Warrell DA. Severe cytomegalovirus infection in immunocompetent patients. Clin Infect Dis. 1997;24(1):52–56.
    1. Rafailidis PI, Mourtzoukou EG, Varbobitis IC, Falagas ME. Severe cytomegalovirus infection in apparently immunocompetent patients: a systematic review. Virol J. 2008;5:47. doi: 10.1186/1743-422X-5-47.
    1. O'Grady NP, Barie PS, Bartlett JG, Bleck T, Carroll K, Kalil AC, Linden P, Maki DG, Nierman D, Pasculle W, Masur H, American College of Critical Care Medicine, Infectious Diseases Society of America Guidelines for evaluation of new fever in critically ill adult patients: 2008 update from the American College of Critical Care Medicine and the Infectious Diseases Society of America. Crit Care Med. 2008;36(4):1330–1349. doi: 10.1097/CCM.0b013e318169eda9.
    1. Egger M, Schneider M, Davey Smith G. Spurious precision? Meta-analysis of observational studies. BMJ. 1998;316(7125):140–144.
    1. Fletcher J. What is heterogeneity and is it important? BMJ. 2007;334(7584):94–96. doi: 10.1136/bmj.39057.406644.68.
    1. Dowling JN, Saslow AR, Armstrong JA, Ho M. Cytomegalovirus infection in patients receiving immunosuppressive therapy for rheumatologic disorders. J Infect Dis. 1976;133(4):399–408.
    1. Sampathkumar P, Paya CV. Management of cytomegalovirus infection after liver transplantation. Liver Transpl. 2000;6(2):144–156.
    1. Wiest PM, Flanigan T, Salata RA, Shlaes DM, Katzman M, Lederman MM. Serious infectious complications of corticosteroid therapy for COPD. Chest. 1989;95(6):1180–1184. doi: 10.1378/chest.95.6.1180.
    1. Marik PE, Pastores SM, Annane D, Meduri GU, Sprung CL, Arlt W, Keh D, Briegel J, Beishuizen A, Dimopoulou I, Tsagarakis S, Singer M, Chrousos GP, Zaloga G, Bokhari F, Vogeser M. Recommendations for the diagnosis and management of corticosteroid insufficiency in critically ill adult patients: consensus statements from an international task force by the American College of Critical Care Medicine. Crit Care Med. 2008;36(6):1937–1949. doi: 10.1097/CCM.0b013e31817603ba.
    1. The Organ Procurement and Transplantation Network
    1. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29(7):1303–1310. doi: 10.1097/00003246-200107000-00002.
    1. Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med. 2003;348(16):1546–1554. doi: 10.1056/NEJMoa022139.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren