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À‰ † š ¨ † † † † † † ÿÿÿÿ Cytomegalovirus Reactivation in Critically-Ill Immunocompetent Patients
Ajit P. Limaye, M.D., Katharine A. Kirby, M.Sc., Gordon D. Rubenfeld, M.D., Wendy M. Leisenring, Sc.D., Eileen M. Bulger, M.D., Margaret J. Neff, M.D., Nicole S. Gibran, M.D., Meei-Li Huang, Ph.D., Tracy K. Santo, B.Sc., Lawrence Corey, M.D., and Michael Boeckh, M.D.
Departments of Laboratory Medicine (A.P.L., T.K.S., M.L.H., L.C.), Medicine (A.P.L., G.D.R., M.J.N., L.C., M.B.), Biostatistics (WML), and Surgery (E.M.B., N.S.G.), University of Washington, and the Programs in Infectious Diseases (M.L.H., L.C., M.B.) and Clinical Statistics (K.A.K., W.M.L.), Fred Hutchinson Cancer Research Center (K.A.K., W.M.L., M.L.H., L.C., M.B.), Seattle, Washington, USA
Presented in part at the American Thoracic Society International Conference (Abstract #406), San Francisco, CA, May 2007
Corresponding Author:
Ajit P. Limaye, MD
Department of Laboratory Medicine
University of Washington Medical Center
1959 NE Pacific Street
Seattle, WA 98195-7110
United States
Tel 206-598-6131
FAX 206-598-6189
E-mail limaye@u.washington.edu
Abstract:
Context: Cytomegalovirus (CMV) infection is associated with adverse clinical outcomes in immunosuppressed persons, but the incidence and association of CMV reactivation with adverse outcomes in persons lacking evidence of immunosuppression (“ immunocompetent”) with critical illness have not been well-defined.
Objective: To determine the association of CMV reactivation with intensive care unit (ICU) and hospital length of stay in critically-ill immunocompetent persons.
Methods: We prospectively assessed CMV plasma DNAemia by real-time PCR twice weekly and clinical outcomes in a cohort of CMV seropositive, immunocompetent adults admitted to an ICU. Clinical parameters were assessed by personnel blinded to CMV PCR results. Risk factors for CMV reactivation and association with hospital and ICU length of stay (LOS) were assessed by multivariable logistic regression and proportional odds models.
Setting: Six ICU’s at two separate hospitals at a large tertiary care academic medical center between 2004-2006.
Participants: A total of 120 critically-ill, CMV seropositive adults lacking evidence of immunosuppression.
Main Outcome Measures: Association of CMV reactivation with prolonged hospital length of stay or death.
Results: The primary composite endpoint of continued hospitalization (n=35) or death (n=10) at 30 days occurred in 45 (35%) of the 120 patients. CMV viremia at any level or > 1,000 copies/ml occurred in 33% (39 of 120, 95% confidence interval [CI] 24%-41%) and 20% (24 of 120, 95% CI 13%-28%), at a median of 12 days (range 3-57) and 26 days (range 9-56), respectively. By logistic regression, CMV infection at any level (adjusted OR: 4.3 [1.6-11.9], p = 0.005), >1,000 copies/ml (adjusted OR 13.9 [3.2-60], p < 0.001), or average CMV area under the curve [AUC] (adjusted OR 2.1 [1.3-3.2], p < 0.001), was independently associated with hospitalization or death by 30 days. In multivariable partial proportional odds models, both CMV seven-day moving average (OR 5.1 (2.9-9.1) p < 0.0001) and CMV AUC (OR 3.2 (2.1-4.7), p < 0.0001) were independently associated with a hospital LOS >14 days.
Conclusions: These preliminary findings suggest that reactivation of CMV occurs frequently in critically-ill immunocompetent patients and is associated with prolonged hospitalization or death. A controlled trial of CMV prophylaxis in this setting is warranted.
Introduction
Cytomegalovirus (CMV) has long been recognized as an important viral pathogen in immunocompromised hosts. In addition to direct effects of CMV due to viral replication and resultant tissue injury, a range of indirect effects have been attributed to CMV in immunocompromised patients, including increased risk of secondary bacterial and fungal infections, ADDIN EN.CITE George1997171717George, M. J.Snydman, D. R.Werner, B. G.Griffith, J.Falagas, M. E.Dougherty, N. N.Rubin, R. H.Department of Medicine, New England Medical Center, Boston, Massachusetts 02111, USA.The independent role of cytomegalovirus as a risk factor for invasive fungal disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG-Study Group. Cytogam, MedImmune, Inc. Gaithersburg, MarylandAm J MedAm J Med106-131032AdolescentAdultAnti-Infective Agents/therapeutic use*Cytomegalovirus/immunologyCytomegalovirus Infections/*etiology/mortality*Graft SurvivalHumansImmunization, Passive/methodsIncidenceLiver Transplantation/*adverse effects/mortalityMiddle AgedOpportunistic Infections/*microbiologyProportional Hazards ModelsRandomized Controlled TrialsRetrospective StudiesRisk FactorsTime FactorsTreatment Outcome1997Aug9274893http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9274893Hodson2005202017Hodson, E. M.Jones, C. A.Webster, A. C.Strippoli, G. F.Barclay, P. G.Kable, K.Vimalachandra, D.Craig, J. C.National Health and Medical Research Council Centre for Clinical Research Excellence, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. Elisah@chw.edu.auAntiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trialsLancetLancet2105-153659477Acyclovir/analogs & derivatives/therapeutic useAntiviral Agents/*therapeutic useCytomegalovirus Infections/*prevention & controlGanciclovir/therapeutic useGraft RejectionHumansOpportunistic Infections/*prevention & control*Organ Transplantation/mortalityRandomized Controlled TrialsValine/analogs & derivatives/therapeutic use2005Jun 18-2415964447http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15964447Kalil2005242417Kalil, A. C.Levitsky, J.Lyden, E.Stoner, J.Freifeld, A. G.University of Nebraska Medical Center, Omaha, Nebraska 68198-5400, USA. akalil@unmc.eduMeta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipientsAnn Intern MedAnn Intern Med870-8014312Antiviral Agents/*therapeutic useCytomegalovirus Infections/*prevention & controlHumansImmunocompromised HostKidney Transplantation/*immunologyLiver Transplantation/*immunologyOpportunistic Infections/*prevention & controlSensitivity and Specificity2005Dec 2016365468http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16365468Small2006393917Small, L. N.Lau, J.Snydman, D. R.Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02446, USA.Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapiesClin Infect DisClin Infect Dis869-80437Antiviral Agents/*therapeutic useCytomegalovirus Infections/etiology/mortality/*prevention & controlGanciclovir/*therapeutic useHumansOpportunistic Infections/etiology/prevention & controlOrgan Transplantation/*adverse effectsPreventive Medicine2006Oct 116941368http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16941368Strippoli2006404017Strippoli, G. F.Hodson, E. M.Jones, C.Craig, J. C.NHMRC Centre for Clinical Research Excellence in Renal Medicine, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. gfmstippoli@aliceposta.itPreemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipientsTransplantationTransplantation139-45812Antiviral Agents/administration & dosage/therapeutic useCytomegalovirus Infections/*drug therapy/etiology/*prevention & controlGanciclovir/administration & dosageHumansOpportunistic Infections/*drug therapy/etiology/*prevention & controlRandomized Controlled TrialsTransplants/*adverse effectsViremia/*drug therapy/etiology/*prevention & control2006Jan 2716436954http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=164369541-5 predisposition to specific malignancies such as EBV-associated post-transplant lymphoproliferative disorder, ADDIN EN.CITE Manez1997313117Manez, R.Breinig, M. C.Linden, P.Wilson, J.Torre-Cisneros, J.Kusne, S.Dummer, S.Ho, M.Pittsburgh Transplantation Institute, Department of Surgery, Graduate School of Public Health, University of Pittsburgh, Pennsylvania 15261, USA.Posttransplant lymphoproliferative disease in primary Epstein-Barr virus infection after liver transplantation: the role of cytomegalovirus diseaseJ Infect DisJ Infect Dis1462-71766AdultBiological MarkersCytomegalovirus Infections/*complications/diagnosis/epidemiologyFemaleHerpesviridae Infections/diagnosis/epidemiology/*etiology*Herpesvirus 4, HumanHumansImmunosuppression/adverse effectsIncidenceLiver Transplantation/*adverse effectsLymphoproliferative Disorders/diagnosis/epidemiology/*etiologyMaleMiddle AgedRetrospective StudiesRisk Factors1997Dec9395355http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=93953556 cardiovascular disease, ADDIN EN.CITE Kalil2003232317Kalil, R. S.Hudson, S. L.Gaston, R. S.Departments of Medicine and Surgery, University of Alabama at Birmingham, Birmingham, AL, USA.Determinants of cardiovascular mortality after renal transplantation: a role for cytomegalovirus?Am J TransplantAm J Transplant79-8131Antilymphocyte Serum/pharmacologyCardiovascular Diseases/*mortalityCytomegalovirus Infections/immunology/*mortalityHumansImmunosuppressive Agents/pharmacology*Kidney TransplantationMuromonab-CD3/pharmacology2003Jan12492715http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12492715Valantine1999424217Valantine, H. A.Gao, S. Z.Menon, S. G.Renlund, D. G.Hunt, S. A.Oyer, P.Stinson, E. B.Brown, B. W., Jr.Merigan, T. C.Schroeder, J. S.Stanford University School of Medicine, Stanford, CA, USA.Impact of prophylactic immediate posttransplant ganciclovir on development of transplant atherosclerosis: a post hoc analysis of a randomized, placebo-controlled studyCirculationCirculation61-61001Actuarial AnalysisAdultAgedAntibodies, Viral/bloodAntiviral Agents/*therapeutic useCalcium Channel Blockers/therapeutic useCause of DeathCoronary Arteriosclerosis/epidemiology/etiology/*prevention &control/virologyCytomegalovirus/immunologyCytomegalovirus Infections/complications/drug therapy/epidemiologyFemaleFollow-Up StudiesGanciclovir/*therapeutic useHeart Transplantation/*adverse effectsHumansImmunosuppression/adverse effectsIncidenceMaleMiddle AgedPostoperative Complications/drug therapy/epidemiology/etiology/*prevention& control/virologyProportional Hazards ModelsReoperationRiskSeroepidemiologic StudiesTreatment Outcome1999Jul 610393682http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=103936827, 8 and mortality. ADDIN EN.CITE Hodson2005202017Hodson, E. M.Jones, C. A.Webster, A. C.Strippoli, G. F.Barclay, P. G.Kable, K.Vimalachandra, D.Craig, J. C.National Health and Medical Research Council Centre for Clinical Research Excellence, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. Elisah@chw.edu.auAntiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trialsLancetLancet2105-153659477Acyclovir/analogs & derivatives/therapeutic useAntiviral Agents/*therapeutic useCytomegalovirus Infections/*prevention & controlGanciclovir/therapeutic useGraft RejectionHumansOpportunistic Infections/*prevention & control*Organ Transplantation/mortalityRandomized Controlled TrialsValine/analogs & derivatives/therapeutic use2005Jun 18-2415964447http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15964447Kalil2005242417Kalil, A. C.Levitsky, J.Lyden, E.Stoner, J.Freifeld, A. G.University of Nebraska Medical Center, Omaha, Nebraska 68198-5400, USA. akalil@unmc.eduMeta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipientsAnn Intern MedAnn Intern Med870-8014312Antiviral Agents/*therapeutic useCytomegalovirus Infections/*prevention & controlHumansImmunocompromised HostKidney Transplantation/*immunologyLiver Transplantation/*immunologyOpportunistic Infections/*prevention & controlSensitivity and Specificity2005Dec 2016365468http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16365468Limaye2006282817Limaye, A. P.Bakthavatsalam, R.Kim, H. W.Randolph, S. E.Halldorson, J. B.Healey, P. J.Kuhr, C. S.Levy, A. E.Perkins, J. D.Reyes, J. D.Boeckh, M.Department of Laboratory Medicine, University of Washington, Seattle, WA 98195-7110, USA. limaye@u.washington.eduImpact of cytomegalovirus in organ transplant recipients in the era of antiviral prophylaxisTransplantationTransplantation1645-528112Antiviral Agents/*pharmacologyCohort StudiesCytomegalovirus/*drug effects/*physiologyCytomegalovirus Infections/mortality/pathology/*prevention &control/virologyFemaleHumans*Liver TransplantationMaleMiddle AgedRisk FactorsTime Factors2006Jun 2716794529http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16794529Sagedal2004383817Sagedal, S.Hartmann, A.Nordal, K. P.Osnes, K.Leivestad, T.Foss, A.Degre, M.Fauchald, P.Rollag, H.Department of Internal Medicine, Laboratory for Renal Physiology, Institute of Biostatistics, Rikshospitalet University Hospital, Oslo, Norway. solbjorg.sagedal@rikshospitalet.noImpact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survivalKidney IntKidney Int329-37661AdolescentAdultAgedAged, 80 and overCause of DeathCohort StudiesCreatinine/bloodCytomegalovirus Infections/drug therapy/*etiologyFemaleGraft Rejection/epidemiology*Graft SurvivalHospitalizationHumansIncidenceKidney/physiopathologyKidney Transplantation/*adverse effects/*mortalityMaleMiddle AgedRisk FactorsSurvival AnalysisTime Factors2004Jul15200441http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15200441Small2006393917Small, L. N.Lau, J.Snydman, D. R.Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02446, USA.Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapiesClin Infect DisClin Infect Dis869-80437Antiviral Agents/*therapeutic useCytomegalovirus Infections/etiology/mortality/*prevention & controlGanciclovir/*therapeutic useHumansOpportunistic Infections/etiology/prevention & controlOrgan Transplantation/*adverse effectsPreventive Medicine2006Oct 116941368http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16941368Strippoli2006404017Strippoli, G. F.Hodson, E. M.Jones, C.Craig, J. C.NHMRC Centre for Clinical Research Excellence in Renal Medicine, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. gfmstippoli@aliceposta.itPreemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipientsTransplantationTransplantation139-45812Antiviral Agents/administration & dosage/therapeutic useCytomegalovirus Infections/*drug therapy/etiology/*prevention & controlGanciclovir/administration & dosageHumansOpportunistic Infections/*drug therapy/etiology/*prevention & controlRandomized Controlled TrialsTransplants/*adverse effectsViremia/*drug therapy/etiology/*prevention & control2006Jan 2716436954http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=164369542-5, 9, 10 A causal role of CMV in mediating these indirect effects is supported by studies of antiviral prophylaxis in immunosuppressed patients demonstrating reductions in secondary bacterial and fungal infections, ADDIN EN.CITE Hodson2005202017Hodson, E. M.Jones, C. A.Webster, A. C.Strippoli, G. F.Barclay, P. G.Kable, K.Vimalachandra, D.Craig, J. C.National Health and Medical Research Council Centre for Clinical Research Excellence, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. Elisah@chw.edu.auAntiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trialsLancetLancet2105-153659477Acyclovir/analogs & derivatives/therapeutic useAntiviral Agents/*therapeutic useCytomegalovirus Infections/*prevention & controlGanciclovir/therapeutic useGraft RejectionHumansOpportunistic Infections/*prevention & control*Organ Transplantation/mortalityRandomized Controlled TrialsValine/analogs & derivatives/therapeutic use2005Jun 18-2415964447http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15964447Kalil2005242417Kalil, A. C.Levitsky, J.Lyden, E.Stoner, J.Freifeld, A. G.University of Nebraska Medical Center, Omaha, Nebraska 68198-5400, USA. akalil@unmc.eduMeta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipientsAnn Intern MedAnn Intern Med870-8014312Antiviral Agents/*therapeutic useCytomegalovirus Infections/*prevention & controlHumansImmunocompromised HostKidney Transplantation/*immunologyLiver Transplantation/*immunologyOpportunistic Infections/*prevention & controlSensitivity and Specificity2005Dec 2016365468http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16365468Small2006393917Small, L. N.Lau, J.Snydman, D. R.Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02446, USA.Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapiesClin Infect DisClin Infect Dis869-80437Antiviral Agents/*therapeutic useCytomegalovirus Infections/etiology/mortality/*prevention & controlGanciclovir/*therapeutic useHumansOpportunistic Infections/etiology/prevention & controlOrgan Transplantation/*adverse effectsPreventive Medicine2006Oct 116941368http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16941368Strippoli2006404017Strippoli, G. F.Hodson, E. M.Jones, C.Craig, J. C.NHMRC Centre for Clinical Research Excellence in Renal Medicine, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. gfmstippoli@aliceposta.itPreemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipientsTransplantationTransplantation139-45812Antiviral Agents/administration & dosage/therapeutic useCytomegalovirus Infections/*drug therapy/etiology/*prevention & controlGanciclovir/administration & dosageHumansOpportunistic Infections/*drug therapy/etiology/*prevention & controlRandomized Controlled TrialsTransplants/*adverse effectsViremia/*drug therapy/etiology/*prevention & control2006Jan 2716436954http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=164369542-5 hospitalization, ADDIN EN.CITE Lowance1999303017Lowance, D.Neumayer, H. H.Legendre, C. M.Squifflet, J. P.Kovarik, J.Brennan, P. J.Norman, D.Mendez, R.Keating, M. R.Coggon, G. L.Crisp, A.Lee, I. C.Department of Internal Medicine, Piedmont Hospital, Atlanta, GA 30367, USA. dlowa80715@aol.comValacyclovir for the prevention of cytomegalovirus disease after renal transplantation. International Valacyclovir Cytomegalovirus Prophylaxis Transplantation Study GroupN Engl J MedN Engl J Med1462-7034019Acyclovir/adverse effects/*analogs & derivatives/therapeutic useAdultAntiviral Agents/adverse effects/*therapeutic useCadaverCytomegalovirus/isolation & purificationCytomegalovirus Infections/*prevention & controlDouble-Blind MethodFemaleGraft RejectionHealth Resources/utilizationHumansIncidence*Kidney TransplantationMaleMiddle AgedPostoperative Complications/*prevention & controlProdrugs/therapeutic useSerologic TestsValine/adverse effects/*analogs & derivatives/therapeutic use1999May 1310320384http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1032038411 and mortality. ADDIN EN.CITE Hodson2005202017Hodson, E. M.Jones, C. A.Webster, A. C.Strippoli, G. F.Barclay, P. G.Kable, K.Vimalachandra, D.Craig, J. C.National Health and Medical Research Council Centre for Clinical Research Excellence, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. Elisah@chw.edu.auAntiviral medications to prevent cytomegalovirus disease and early death in recipients of solid-organ transplants: a systematic review of randomised controlled trialsLancetLancet2105-153659477Acyclovir/analogs & derivatives/therapeutic useAntiviral Agents/*therapeutic useCytomegalovirus Infections/*prevention & controlGanciclovir/therapeutic useGraft RejectionHumansOpportunistic Infections/*prevention & control*Organ Transplantation/mortalityRandomized Controlled TrialsValine/analogs & derivatives/therapeutic use2005Jun 18-2415964447http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15964447Kalil2005242417Kalil, A. C.Levitsky, J.Lyden, E.Stoner, J.Freifeld, A. G.University of Nebraska Medical Center, Omaha, Nebraska 68198-5400, USA. akalil@unmc.eduMeta-analysis: the efficacy of strategies to prevent organ disease by cytomegalovirus in solid organ transplant recipientsAnn Intern MedAnn Intern Med870-8014312Antiviral Agents/*therapeutic useCytomegalovirus Infections/*prevention & controlHumansImmunocompromised HostKidney Transplantation/*immunologyLiver Transplantation/*immunologyOpportunistic Infections/*prevention & controlSensitivity and Specificity2005Dec 2016365468http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16365468Small2006393917Small, L. N.Lau, J.Snydman, D. R.Division of Geographic Medicine and Infectious Diseases, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts 02446, USA.Preventing post-organ transplantation cytomegalovirus disease with ganciclovir: a meta-analysis comparing prophylactic and preemptive therapiesClin Infect DisClin Infect Dis869-80437Antiviral Agents/*therapeutic useCytomegalovirus Infections/etiology/mortality/*prevention & controlGanciclovir/*therapeutic useHumansOpportunistic Infections/etiology/prevention & controlOrgan Transplantation/*adverse effectsPreventive Medicine2006Oct 116941368http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=16941368Strippoli2006404017Strippoli, G. F.Hodson, E. M.Jones, C.Craig, J. C.NHMRC Centre for Clinical Research Excellence in Renal Medicine, Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia. gfmstippoli@aliceposta.itPreemptive treatment for cytomegalovirus viremia to prevent cytomegalovirus disease in solid organ transplant recipientsTransplantationTransplantation139-45812Antiviral Agents/administration & dosage/therapeutic useCytomegalovirus Infections/*drug therapy/etiology/*prevention & controlGanciclovir/administration & dosageHumansOpportunistic Infections/*drug therapy/etiology/*prevention & controlRandomized Controlled TrialsTransplants/*adverse effectsViremia/*drug therapy/etiology/*prevention & control2006Jan 2716436954http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=164369542-5
The role of CMV infection in immunocompetent patients with critical illness has been investigated in several prior studies. ADDIN EN.CITE Bale1990474717Bale, J. F., Jr.Kealey, G. P.Massanari, R. M.Strauss, R. G.Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242.The epidemiology of cytomegalovirus infection among patients with burnsInfect Control Hosp EpidemiolInfect Control Hosp Epidemiol17-22111AdolescentAdultAgedBlood TransfusionBurn UnitsBurns/*complications/diagnosis/surgeryChildChild, PreschoolCytomegalovirus Infections/blood/*epidemiology/etiologyFemaleHospitals, UniversityHumansInfantIowaMaleMiddle AgedProspective StudiesSkin Transplantation1990Jan2153725http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2153725Cook2003101017Cook, C. H.Martin, L. C.Yenchar, J. K.Lahm, M. C.McGuinness, B.Davies, E. A.Ferguson, R. M.Department of Surgery, The Ohio State University, Columbus, USA.Occult herpes family viral infections are endemic in critically ill surgical patientsCrit Care MedCrit Care Med1923-9317ApacheCD4-CD8 RatioCausalityCritical Illness/*epidemiologyCross Infection/*epidemiology/immunologyCross-Sectional StudiesCytomegalovirus Infections/*epidemiology/immunology*Endemic DiseasesFemaleHerpes Simplex/*epidemiology/immunologyHumansIntensive Care/*statistics & numerical dataMaleMiddle AgedProspective Studies2003Jul12847384http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12847384Cook19989917Cook, C. H.Yenchar, J. K.Kraner, T. O.Davies, E. A.Ferguson, R. M.Ohio State University Department of Surgery, Columbus, USA.Occult herpes family viruses may increase mortality in critically ill surgical patientsAm J SurgAm J Surg357-601764Aged*Critical IllnessCytomegalovirus Infections/*mortalityFemaleHerpes Simplex/*mortalityHumansImmunosuppressionIntensive Care Units/*statistics & numerical dataMaleMiddle AgedMultiple Organ Failure/*mortalityPostoperative Complications/virologyRetrospective StudiesSurgical Procedures, Operative1998Oct9817255http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9817255Domart1990121217Domart, Y.Trouillet, J. L.Fagon, J. Y.Chastre, J.Brun-Vezinet, F.Gibert, C.Service de Reanimation Medicale, Hopital Bichat, Paris, France.Incidence and morbidity of cytomegaloviral infection in patients with mediastinitis following cardiac surgeryChestChest18-22971Antibodies, Viral/analysis*Cardiac Surgical ProceduresCytomegalovirus/immunology/isolation & purificationCytomegalovirus Infections/*etiology/microbiology/therapyFemaleHumansImmunoglobulin G/analysisMaleMediastinitis/*etiology/microbiology/therapyMiddle Aged*Postoperative ComplicationsViremia/microbiology1990Jan2153065http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2153065Heininger2001191917Heininger, A.Jahn, G.Engel, C.Notheisen, T.Unertl, K.Hamprecht, K.Klinik fur Anasthesiologie und Transfusionsmedizin, Institut fur Anasthesiologie, Universitatsklinikum Tubingen, Germany. alexandra.heininger@med.uni-tuebingen.deHuman cytomegalovirus infections in nonimmunosuppressed critically ill patientsCrit Care MedCrit Care Med541-7293ApacheAgedAnalysis of VarianceAntibodies, Viral/blood*Critical Illness/mortalityCytomegalovirus/immunologyCytomegalovirusInfections/blood/diagnosis/*etiology/immunology/mortality/virologyFemaleGermany/epidemiologyHospital MortalityHospitals, UniversityHumans*ImmunocompetenceImmunoglobulin G/immunologyIntensive CareLogistic ModelsMaleMiddle AgedMultiple Trauma/complicationsOdds RatioPostoperativeComplications/blood/diagnosis/*etiology/immunology/mortality/virologyProportional Hazards ModelsProspective StudiesRisk FactorsSepsis/complicationsSurvival Analysis2001Mar11373417http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11373417Jaber2005212117Jaber, S.Chanques, G.Borry, J.Souche, B.Verdier, R.Perrigault, P. F.Eledjam, J. J.Intensive Care Unit and Transplantation Department, Saint Eloi Hospital, University Hospital of Montpellier, Montpellier, France. s-jaber@chu-montpellier.frCytomegalovirus infection in critically ill patients: associated factors and consequencesChestChest233-411271AdultAntigens, Viral/bloodComorbidityCritical Illness/*epidemiologyCytomegalovirus/immunologyCytomegalovirus Infections/*epidemiologyFemaleHumansMaleMiddle Aged2005Jan15653989http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15653989Kealey1987252517Kealey, G. P.Bale, J. F.Strauss, R. G.Massanari, R. M.Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City 52242.Cytomegalovirus infection in burn patientsJ Burn Care RehabilJ Burn Care Rehabil543-586Antibodies, Viral/*analysisBurns/*complicationsCytomegalovirus Infections/*diagnosisHumansProspective StudiesRisk FactorsWound Infection/diagnosis/*etiology1987Nov-Dec2830289http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2830289Kutza1998272717Kutza, A. S.Muhl, E.Hackstein, H.Kirchner, H.Bein, G.Department of Surgery, University of Lubeck School of Medicine, Germany.High incidence of active cytomegalovirus infection among septic patientsClin Infect DisClin Infect Dis1076-82265Antibodies, Viral/bloodAntigens, Viral/bloodBlotting, SouthernCytokines/bloodCytomegalovirus/immunologyCytomegalovirus Infections/*complications/diagnosis/*epidemiologyDNA, Viral/bloodEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoglobulin G/bloodImmunohistochemistryIncidenceLongitudinal StudiesMaleMiddle AgedPhosphoproteins/bloodPolymerase Chain ReactionProspective StudiesSepsis/*complicationsViral Matrix Proteins/blood1998May9597229http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9597229von Muller2006434317von Muller, L.Klemm, A.Weiss, M.Schneider, M.Suger-Wiedeck, H.Durmus, N.Hampl, W.Mertens, T.University Hospital Ulm, Ulm, Germany.Active cytomegalovirus infection in patients with septic shockEmerg Infect DisEmerg Infect Dis1517-221210AdultAgedCytomegalovirus/*isolation & purificationCytomegalovirus Infections/complications/*immunology/therapy/virologyFemaleHerpes Simplex/complications/virologyHumansMaleMiddle AgedPhosphoproteins/immunology/metabolismPilot ProjectsProspective StudiesShock, Septic/immunology/*virologySimplexvirus/isolation & purificationViral Matrix Proteins/immunology/metabolism2006Oct17176565http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1717656512-20 Although these studies used various virologic and statistical methods and designs, most demonstrated that CMV infection occurs commonly in critically-ill patients and is associated with one or more adverse clinical outcomes. ADDIN EN.CITE Bale1990474717Bale, J. F., Jr.Kealey, G. P.Massanari, R. M.Strauss, R. G.Department of Pediatrics, University of Iowa College of Medicine, Iowa City 52242.The epidemiology of cytomegalovirus infection among patients with burnsInfect Control Hosp EpidemiolInfect Control Hosp Epidemiol17-22111AdolescentAdultAgedBlood TransfusionBurn UnitsBurns/*complications/diagnosis/surgeryChildChild, PreschoolCytomegalovirus Infections/blood/*epidemiology/etiologyFemaleHospitals, UniversityHumansInfantIowaMaleMiddle AgedProspective StudiesSkin Transplantation1990Jan2153725http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2153725Cook2003101017Cook, C. H.Martin, L. C.Yenchar, J. K.Lahm, M. C.McGuinness, B.Davies, E. A.Ferguson, R. M.Department of Surgery, The Ohio State University, Columbus, USA.Occult herpes family viral infections are endemic in critically ill surgical patientsCrit Care MedCrit Care Med1923-9317ApacheCD4-CD8 RatioCausalityCritical Illness/*epidemiologyCross Infection/*epidemiology/immunologyCross-Sectional StudiesCytomegalovirus Infections/*epidemiology/immunology*Endemic DiseasesFemaleHerpes Simplex/*epidemiology/immunologyHumansIntensive Care/*statistics & numerical dataMaleMiddle AgedProspective Studies2003Jul12847384http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12847384Cook19989917Cook, C. H.Yenchar, J. K.Kraner, T. O.Davies, E. A.Ferguson, R. M.Ohio State University Department of Surgery, Columbus, USA.Occult herpes family viruses may increase mortality in critically ill surgical patientsAm J SurgAm J Surg357-601764Aged*Critical IllnessCytomegalovirus Infections/*mortalityFemaleHerpes Simplex/*mortalityHumansImmunosuppressionIntensive Care Units/*statistics & numerical dataMaleMiddle AgedMultiple Organ Failure/*mortalityPostoperative Complications/virologyRetrospective StudiesSurgical Procedures, Operative1998Oct9817255http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9817255Domart1990121217Domart, Y.Trouillet, J. L.Fagon, J. Y.Chastre, J.Brun-Vezinet, F.Gibert, C.Service de Reanimation Medicale, Hopital Bichat, Paris, France.Incidence and morbidity of cytomegaloviral infection in patients with mediastinitis following cardiac surgeryChestChest18-22971Antibodies, Viral/analysis*Cardiac Surgical ProceduresCytomegalovirus/immunology/isolation & purificationCytomegalovirus Infections/*etiology/microbiology/therapyFemaleHumansImmunoglobulin G/analysisMaleMediastinitis/*etiology/microbiology/therapyMiddle Aged*Postoperative ComplicationsViremia/microbiology1990Jan2153065http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2153065Heininger2001191917Heininger, A.Jahn, G.Engel, C.Notheisen, T.Unertl, K.Hamprecht, K.Klinik fur Anasthesiologie und Transfusionsmedizin, Institut fur Anasthesiologie, Universitatsklinikum Tubingen, Germany. alexandra.heininger@med.uni-tuebingen.deHuman cytomegalovirus infections in nonimmunosuppressed critically ill patientsCrit Care MedCrit Care Med541-7293ApacheAgedAnalysis of VarianceAntibodies, Viral/blood*Critical Illness/mortalityCytomegalovirus/immunologyCytomegalovirusInfections/blood/diagnosis/*etiology/immunology/mortality/virologyFemaleGermany/epidemiologyHospital MortalityHospitals, UniversityHumans*ImmunocompetenceImmunoglobulin G/immunologyIntensive CareLogistic ModelsMaleMiddle AgedMultiple Trauma/complicationsOdds RatioPostoperativeComplications/blood/diagnosis/*etiology/immunology/mortality/virologyProportional Hazards ModelsProspective StudiesRisk FactorsSepsis/complicationsSurvival Analysis2001Mar11373417http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11373417Jaber2005212117Jaber, S.Chanques, G.Borry, J.Souche, B.Verdier, R.Perrigault, P. F.Eledjam, J. J.Intensive Care Unit and Transplantation Department, Saint Eloi Hospital, University Hospital of Montpellier, Montpellier, France. s-jaber@chu-montpellier.frCytomegalovirus infection in critically ill patients: associated factors and consequencesChestChest233-411271AdultAntigens, Viral/bloodComorbidityCritical Illness/*epidemiologyCytomegalovirus/immunologyCytomegalovirus Infections/*epidemiologyFemaleHumansMaleMiddle Aged2005Jan15653989http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15653989Kealey1987252517Kealey, G. P.Bale, J. F.Strauss, R. G.Massanari, R. M.Department of Surgery, University of Iowa Hospitals and Clinics, Iowa City 52242.Cytomegalovirus infection in burn patientsJ Burn Care RehabilJ Burn Care Rehabil543-586Antibodies, Viral/*analysisBurns/*complicationsCytomegalovirus Infections/*diagnosisHumansProspective StudiesRisk FactorsWound Infection/diagnosis/*etiology1987Nov-Dec2830289http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2830289Kutza1998272717Kutza, A. S.Muhl, E.Hackstein, H.Kirchner, H.Bein, G.Department of Surgery, University of Lubeck School of Medicine, Germany.High incidence of active cytomegalovirus infection among septic patientsClin Infect DisClin Infect Dis1076-82265Antibodies, Viral/bloodAntigens, Viral/bloodBlotting, SouthernCytokines/bloodCytomegalovirus/immunologyCytomegalovirus Infections/*complications/diagnosis/*epidemiologyDNA, Viral/bloodEnzyme-Linked Immunosorbent AssayFemaleHumansImmunoglobulin G/bloodImmunohistochemistryIncidenceLongitudinal StudiesMaleMiddle AgedPhosphoproteins/bloodPolymerase Chain ReactionProspective StudiesSepsis/*complicationsViral Matrix Proteins/blood1998May9597229http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9597229von Muller2006434317von Muller, L.Klemm, A.Weiss, M.Schneider, M.Suger-Wiedeck, H.Durmus, N.Hampl, W.Mertens, T.University Hospital Ulm, Ulm, Germany.Active cytomegalovirus infection in patients with septic shockEmerg Infect DisEmerg Infect Dis1517-221210AdultAgedCytomegalovirus/*isolation & purificationCytomegalovirus Infections/complications/*immunology/therapy/virologyFemaleHerpes Simplex/complications/virologyHumansMaleMiddle AgedPhosphoproteins/immunology/metabolismPilot ProjectsProspective StudiesShock, Septic/immunology/*virologySimplexvirus/isolation & purificationViral Matrix Proteins/immunology/metabolism2006Oct17176565http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1717656512-20 However, these prior studies had one or more significant limitations, including relatively small sample size, inclusion of only selected types of ICU patients, lack of quantitative methods for CMV detection, non-blinded assessment of clinical endpoints, and/or failure to include comprehensive and rigorous statistical analyses. To address some of these limitations, we prospectively assessed CMV plasma DNAemia by real-time PCR and clinical outcomes in a broad cohort of consecutive CMV seropositive, immunocompetent adults admitted to an intensive care unit (ICU), with the goal of defining the incidence, risk factors, timing, and association of CMV reactivation with clinically-significant outcomes.
Methods
Study Design
This prospective study was conducted at six intensive care units (ICU) at two separate hospitals at a large university-affiliated academic medical center between 2004 and 2006. The study was approved by the human subjects division at the University of Washington and written informed consent was obtained from study participants. Daily screening of new medical-surgical admissions to each ICU (Burn [BICU], Cardiac Care [CICU], Medical [MICU], and Trauma [TICU]) was performed by study personnel, and patients who met other inclusion criteria underwent screening with CMV serology within 24 hours. All patients meeting study inclusion criteria were offered participation regardless of race or ethnic status. Participants’ race/ethnic status was recorded as listed in the admitting/registration information, and was collected in compliance with reporting requirements for National Institutes of Health-funded clinical studies. Only patients who were newly admitted to the ICU from home or baseline residential setting were included (i.e., patients who were transferred to the ICU from within the hospital were excluded). Those who were CMV seronegative were excluded from further study. CMV seropositive patients who met all other inclusion criteria were enrolled and underwent prospective clinical assessments using standardized data collection forms. In addition, plasma samples were collected thrice weekly and stored at –20(C for subsequent CMV PCR analysis. All clinical information was collected prospectively by study personnel who were blinded to the CMV PCR results (which were performed after all clinical data had been compiled). Patients were followed prospectively until death or hospital discharge. Deaths occurring within 90 days after discharge from the hospital were assessed using state and national death registry data.
Inclusion and exclusion criteria
The inclusion criteria included: able to give informed consent (either from patient or next of kin), age > 18 years, admission to the Burn intensive care unit (BICU) with > 40% body surface burn or > 20% body surface burn with inhalation injury or Trauma intensive care unit (TICU) with ISS score of >15 AND > 4U packed red blood cells within 24 hours or Medical intensive care unit (MICU) with suspected or documented sepsis or Cardiac intensive care unit (CICU) with a diagnosis of acute myocardial infarction, expected survival > 72 hours, and CMV seropositive. The exclusion criteria were: unable to give informed consent, age < 18 years, expected survival < 72 hours, use of antiviral agent cidofovir, foscarnet, ganciclovir, valacyclovir [HSV treatment doses of acyclovir, valacyclovir, or famciclovir permitted]) within the last 7 days, known or suspected HIV infection, and known or suspected underlying immune deficiency (transplant, congenital immunodeficiency, receipt of immunosuppressive medications [prednisone, azathioprine, tacrolimus, cyclosporin, sirolimus, cyclophosphamide] within 30 days).
Definitions
Major infections included pneumonia or bacteremia. Pneumonia was diagnosed on the basis of radiographic pulmonary infiltrates and a quantitative bacterial culture of BAL demonstrating > 104 cfu/ml as previously defined. ADDIN EN.CITE Chastre19955517Chastre, J.Fagon, J. Y.Bornet-Lecso, M.Calvat, S.Dombret, M. C.al Khani, R.Basset, F.Gibert, C.Service Central de Microbiologie, Hopital Bichat, Paris, France.Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumoniaAm J Respir Crit Care MedAm J Respir Crit Care Med231-401521AgedBiopsy/methodsBronchoalveolar Lavage Fluid/microbiologyBronchoscopy/*methodsCritical IllnessCross Infection/*diagnosis/microbiology/mortalityEvaluation StudiesFemaleFiber OpticsHumansLung/microbiology/pathologyMalePneumonia, Bacterial/*diagnosis/microbiology/mortalityProspective StudiesRespiration, ArtificialSensitivity and SpecificitySpecimen Handling/methods1995Jul7599829http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=759982921 An episode of clinically-significant bacteremia was defined as signs or symptoms of infection (fever, leukocytosis) and isolation of a bacterial pathogen from at least 1 blood culture. Bacteremia (single positive blood cultures) due to coagulase negative Staphylococci and other known common blood culture contaminants including diphtheroids and Bacillus spp. was excluded. The APACHE II and Injury Severity Scores were calculated within 24 hours of admission to the ICU as previously described. ADDIN EN.CITE Baker19741117Baker, S. P.O'Neill, B.Haddon, W., Jr.Long, W. B.The injury severity score: a method for describing patients with multiple injuries and evaluating emergency careJ TraumaJ Trauma187-96143Accidents, TrafficAdolescentAdultAge FactorsAgedChildChild, Preschool*Emergency Medical ServicesHumansInfantMarylandMedical RecordsMiddle AgedTimeWounds and Injuries/classification/*diagnosis/mortality1974Mar4814394http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4814394Knaus1985262617Knaus, W. A.Draper, E. A.Wagner, D. P.Zimmerman, J. E.APACHE II: a severity of disease classification systemCrit Care MedCrit Care Med818-291310Acute DiseaseAdultAge FactorsAgedChronic DiseaseCoronary Artery Bypass/mortality*Costs and Cost AnalysisCritical Care/*methods*Diagnosis-Related GroupsDisease/*classification/physiopathologyHumansMiddle AgedPatient AdmissionPrognosisRiskSurgical Procedures, Operative/mortality1985Oct3928249http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=392824922, 23 The term “immunocompetent” was used to describe patients lacking evidence of immunosuppression.
CMV assays
Antibodies to CMV indicating prior CMV infection were assessed using a commercial enzyme immunoassay kit for detection of total antibodies to CMV (“Abbott CMV Total AB EIA”, Abbott Laboratories, Abbott Park, IL). The assay was performed and interpreted according to manufacturer recommendations. CMV DNA was quantified in stored plasma samples using a previously described real-time PCR assay. ADDIN EN.CITE Boeckh20044417Boeckh, M.Huang, M.Ferrenberg, J.Stevens-Ayers, T.Stensland, L.Nichols, W. G.Corey, L.Fred Hutchinson Cancer Research Center and the University of Washington, Seattle, Washington 98109-1024, USA. mboeckh@FHCRC.orgOptimization of quantitative detection of cytomegalovirus DNA in plasma by real-time PCRJ Clin MicrobiolJ Clin Microbiol1142-8423Antigens, Viral/blood/geneticsAntiviral Agents/therapeutic useBase SequenceBronchoalveolar Lavage Fluid/virologyCytomegalovirus/genetics/*isolation & purificationCytomegalovirus Infections/*diagnosis/drug therapy/etiologyDNA PrimersDNA, Viral/*blood/genetics/isolation & purificationEnzyme-Linked Immunosorbent AssayHumansPhosphoproteins/blood/geneticsPolymerase Chain Reaction/*methodsPredictive Value of TestsReproducibility of ResultsSensitivity and SpecificityStem Cell Transplantation/*adverse effectsViral LoadViral Matrix Proteins/blood/genetics2004Mar15004066http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15004066