High incidence of clinically significant cytomegalovirus infection in CMV D+/R+ lung transplant recipients receiving 3 months of antiviral prophylaxis.
Adult
Aged
Antibodies, Viral
/ blood
Antiviral Agents
/ administration & dosage
Cytomegalovirus
/ drug effects
Cytomegalovirus Infections
/ diagnosis
Female
Humans
Immunoglobulin G
/ blood
Immunosuppressive Agents
/ adverse effects
Incidence
Lung Transplantation
/ adverse effects
Male
Middle Aged
Retrospective Studies
Tissue Donors
Transplant Recipients
CMV infection
antiviral prophylaxis
lung transplant
Journal
Transplant infectious disease : an official journal of the Transplantation Society
ISSN: 1399-3062
Titre abrégé: Transpl Infect Dis
Pays: Denmark
ID NLM: 100883688
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
29
12
2018
revised:
27
02
2019
accepted:
31
03
2019
pubmed:
16
4
2019
medline:
18
12
2019
entrez:
16
4
2019
Statut:
ppublish
Résumé
Universal antiviral prophylaxis is the preferred preventive strategy for lung transplant recipients (LTRs) at risk of CMV infection. We compared the risk of CMV infection between CMV D+/R + and D-/R + LTRs after 3 months of prophylaxis. This was a retrospective review of CMV R + LTRs transplanted between 2005 and 2013. Patients dying before completing 3 months, or receiving >180 days of prophylaxis were excluded. The primary outcome was proportion of LTRs who developed CMV infection and clinically significant CMV infection defined as CMV infection leading to preemptive therapy or CMV disease. We analyzed 90 D+/R + and 72 D-/R + with a median follow up of 730 days. CMV infection and disease was more common in D+/R + compared to D-/R+ (CMV infection 66% vs 40%; P = 0.001; CMV disease 13% vs 4% P = 0.045). Fifty-nine patients developed at least one episode of clinically significant CMV infection (41/90 [46%] D+/R + and 18/72 [25%] D-/R + P=0.007) with recurrence occurring in 29 LTRs (49% of patients with previous CMV infection), of which 22 (76%) were CMV D+/R+. Thirty percent had side effects related to CMV therapy. Three months prophylaxis in D+/R + LTRs was associated with high rates of clinically significant CMV infection and recurrences.
Sections du résumé
BACKGROUND
BACKGROUND
Universal antiviral prophylaxis is the preferred preventive strategy for lung transplant recipients (LTRs) at risk of CMV infection. We compared the risk of CMV infection between CMV D+/R + and D-/R + LTRs after 3 months of prophylaxis.
METHODS
METHODS
This was a retrospective review of CMV R + LTRs transplanted between 2005 and 2013. Patients dying before completing 3 months, or receiving >180 days of prophylaxis were excluded. The primary outcome was proportion of LTRs who developed CMV infection and clinically significant CMV infection defined as CMV infection leading to preemptive therapy or CMV disease.
RESULTS
RESULTS
We analyzed 90 D+/R + and 72 D-/R + with a median follow up of 730 days. CMV infection and disease was more common in D+/R + compared to D-/R+ (CMV infection 66% vs 40%; P = 0.001; CMV disease 13% vs 4% P = 0.045). Fifty-nine patients developed at least one episode of clinically significant CMV infection (41/90 [46%] D+/R + and 18/72 [25%] D-/R + P=0.007) with recurrence occurring in 29 LTRs (49% of patients with previous CMV infection), of which 22 (76%) were CMV D+/R+. Thirty percent had side effects related to CMV therapy.
CONCLUSION
CONCLUSIONS
Three months prophylaxis in D+/R + LTRs was associated with high rates of clinically significant CMV infection and recurrences.
Substances chimiques
Antibodies, Viral
0
Antiviral Agents
0
Immunoglobulin G
0
Immunosuppressive Agents
0
Types de publication
Comparative Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13094Informations de copyright
© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Zamora MR. Cytomegalovirus and lung transplantation. Am J Transplant. 2004;4(8):1219-1226.
Beam E, Lesnick T, Kremers W, Kennedy CC, Razonable RR. Cytomegalovirus disease is associated with higher all-cause mortality after lung transplantation despite extended antiviral prophylaxis. Clin Transplant. 2016;30(3):270-278.
Snyder LD, Wang Z, Chen DF, et al. Cytomegalovirus pneumonitis is a risk for bronchiolitis obliterans syndrome in lung transplantation. Am J Respir Crit Care Med. 2010;181(12):1391-1396.
Santos CAQ, Brennan DC, Yusen RD, Olsen MA. Incidence, risk factors and outcomes of delayed-onset cytomegalovirus disease in a large retrospective cohort of lung transplant recipients. Transplantation. 2015;99(8):1658-1666.
Razonable RR, Humar A. Cytomegalovirus in solid organ transplantation. Am J Transplant. 2013;13(Suppl. 4):93-106.
Razonable RR, Hayden RT. Clinical utility of viral load in management of cytomegalovirus infection after solid organ transplantation. Clin Microbiol Rev. 2013;26(4):703-727.
Wreghitt TG, Hakim M, Gray JJ, Kucia S, Wallwork J, English TA. Cytomegalovirus infections in heart and heart and lung transplant recipients. J Clin Pathol. 1988;41(6):660-667.
Schoeppler KE, et al. Late-onset cytomegalovirus (CMV) in lung transplant recipients: can CMV serostatus guide the duration of prophylaxis? Am J Transplant. 2013;13(2):376-382.
Eid AJ, Razonable RR. New developments in the management of cytomegalovirus infection after solid organ transplantation. Drugs. 2010;70(8):965-981.
Monforte V, Sintes H, López-Gallo C, et al. Risk factors, survival, and impact of prophylaxis length in cytomegalovirus-seropositive lung transplant recipients: A prospective, observational, multicenter study. Transpl Infect Dis. 2017;19(3).
Palmer SM, Limaye AP, Banks M, et al. Extended valganciclovir prophylaxis to prevent cytomegalovirus after lung transplantation: a randomized, controlled trial. Ann Intern Med. 2010;152(12):761-769.
Kotton CN, Kumar D, Caliendo AM, et al. Updated international consensus guidelines on the management of cytomegalovirus in solid-organ transplantation. Transplantation. 2013;96(4):333-360.
Kalil AC, Freifeld AG, Lyden ER, Stoner JA. Valganciclovir for cytomegalovirus prevention in solid organ transplant patients: an evidence-based reassessment of safety and efficacy. PLoS ONE. 2009;4(5):e5512.
Mavrakanas TA, Fournier MA, Clairoux S, et al. Neutropenia in kidney and liver transplant recipients: Risk factors and outcomes. Clin Transplant. 2017;31(10).
Zuk DM, Humar A, Weinkauf JG, et al. An international survey of cytomegalovirus management practices in lung transplantation. Transplantation. 2010;90(6):672-676.
Ljungman P, Boeckh M, Hirsch HH, et al. Definitions of cytomegalovirus infection and disease in transplant patients for use in clinical trials. Clin Infect Dis. 2017;64(1):87-91.
Marty FM, Ljungman P, Chemaly RF, et al. Letermovir prophylaxis for cytomegalovirus in hematopoietic-cell transplantation. N Engl J Med. 2017;377(25):2433-2444.
Estenne M, Maurer JR, Boehler A, et al. Bronchiolitis obliterans syndrome 2001: an update of the diagnostic criteria. J Heart Lung Transplant. 2002;21(3):297-310.
Pang XL, Chui L, Fenton J, LeBlanc B, Preiksaitis JK. Comparison of LightCycler-based PCR, COBAS amplicor CMV monitor, and pp65 antigenemia assays for quantitative measurement of cytomegalovirus viral load in peripheral blood specimens from patients after solid organ transplantation. J Clin Microbiol. 2003;41(7):3167-3174.
Hammond SP, Martin ST, Roberts K, et al. Cytomegalovirus disease in lung transplantation: impact of recipient seropositivity and duration of antiviral prophylaxis. Transpl Infect Dis. 2013;15(2):163-170.
Manuel O, Pang XL, Humar A, Kumar D, Doucette K, Preiksaitis JK. An assessment of donor-to-recipient transmission patterns of human cytomegalovirus by analysis of viral genomic variants. J Infect Dis. 2009;199(11):1621-1628.
Ishibashi K, Tokumoto T, Tanabe K, et al. Association of the outcome of renal transplantation with antibody response to cytomegalovirus strain-specific glycoprotein H epitopes. Clin Infect Dis. 2007;45(1):60-67.
Shanahan A, Malani PN, Kaul DR. Relapsing cytomegalovirus infection in solid organ transplant recipients. Transpl Infect Dis. 2009;11(6):513-518.
Natori Y, Humar A, Husain S, et al. Recurrence of CMV infection and the effect of prolonged antivirals in organ transplant recipients. Transplantation. 2017;101(6):1449-1454.
Eid AJ, Arthurs SK, Deziel PJ, Wilhelm MP, Razonable RR. Clinical predictors of relapse after treatment of primary gastrointestinal cytomegalovirus disease in solid organ transplant recipients. Am J Transplant. 2010;10(1):157-161.