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Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients

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@article{d2d9eff4b29b41a1924e9417c344ba75,
title = "Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients",
abstract = "Background: Rates and risk factors for cytomegalovirus (CMV) prophylaxis breakthrough and discontinuation were investigated, given uncertainty regarding optimal dosing for CMV primary (val)ganciclovir prophylaxis after solid organ transplantation (SOT).Methods: Recipients transplanted from 2012 to 2016 and initiated on primary prophylaxis were followed until 90 days post-transplantation. A (val)ganciclovir prophylaxis score for each patient per day was calculated during the follow-up time (FUT; score of 100 corresponding to manufacturers' recommended dose for a given estimated glomerular filtration rate [eGFR]). Cox models were used to estimate hazard ratios (HRs), adjusted for relevant risk factors.Results: Of 585 SOTs (311 kidney, 117 liver, 106 lung, 51 heart) included, 38/585 (6.5{\%}) experienced prophylaxis breakthrough and 35/585 (6.0{\%}) discontinued prophylaxis for other reasons. CMV IgG donor+/receipient- mismatch (adjusted HR [aHR], 5.37; 95{\%} confidence interval [CI], 2.63 to 10.98; P < 0.001) and increasing {\%} FUT with a prophylaxis score <90 (aHR, 1.16; 95{\%} CI, 1.04 to 1.29; P = .01 per 10{\%} longer FUT w/ score <90) were associated with an increased risk of breakthrough. Lung recipients were at a significantly increased risk of premature prophylaxis discontinuation (aHR, 20.2 vs kidney; 95{\%} CI, 3.34 to 121.9; P = .001), mainly due to liver or myelotoxicity.Conclusions: Recipients of eGFR-adjusted prophylaxis doses below those recommended by manufacturers were at an increased risk of prophylaxis breakthrough, emphasizing the importance of accurate dose adjustment according to the latest eGFR and the need for novel, less toxic agents.",
keywords = "CMV, Cytomegalovirus, Ganciclovir, Prophylaxis, SOT, Transplantation, Valganciclovir",
author = "Khurana, {Mark P} and Lodding, {Isabelle P} and Amanda Mocroft and S{\o}rensen, {S{\o}ren S} and Michael Perch and Allan Rasmussen and Finn Gustafsson and Lundgren, {Jens D}",
year = "2019",
month = "6",
day = "3",
doi = "10.1093/ofid/ofz215",
language = "English",
volume = "6",
pages = "ofz215",
journal = "Open Forum Infectious Diseases",
issn = "2328-8957",
publisher = "Oxford University Press",
number = "6",

}

RIS

TY - JOUR

T1 - Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients

AU - Khurana, Mark P

AU - Lodding, Isabelle P

AU - Mocroft, Amanda

AU - Sørensen, Søren S

AU - Perch, Michael

AU - Rasmussen, Allan

AU - Gustafsson, Finn

AU - Lundgren, Jens D

PY - 2019/6/3

Y1 - 2019/6/3

N2 - Background: Rates and risk factors for cytomegalovirus (CMV) prophylaxis breakthrough and discontinuation were investigated, given uncertainty regarding optimal dosing for CMV primary (val)ganciclovir prophylaxis after solid organ transplantation (SOT).Methods: Recipients transplanted from 2012 to 2016 and initiated on primary prophylaxis were followed until 90 days post-transplantation. A (val)ganciclovir prophylaxis score for each patient per day was calculated during the follow-up time (FUT; score of 100 corresponding to manufacturers' recommended dose for a given estimated glomerular filtration rate [eGFR]). Cox models were used to estimate hazard ratios (HRs), adjusted for relevant risk factors.Results: Of 585 SOTs (311 kidney, 117 liver, 106 lung, 51 heart) included, 38/585 (6.5%) experienced prophylaxis breakthrough and 35/585 (6.0%) discontinued prophylaxis for other reasons. CMV IgG donor+/receipient- mismatch (adjusted HR [aHR], 5.37; 95% confidence interval [CI], 2.63 to 10.98; P < 0.001) and increasing % FUT with a prophylaxis score <90 (aHR, 1.16; 95% CI, 1.04 to 1.29; P = .01 per 10% longer FUT w/ score <90) were associated with an increased risk of breakthrough. Lung recipients were at a significantly increased risk of premature prophylaxis discontinuation (aHR, 20.2 vs kidney; 95% CI, 3.34 to 121.9; P = .001), mainly due to liver or myelotoxicity.Conclusions: Recipients of eGFR-adjusted prophylaxis doses below those recommended by manufacturers were at an increased risk of prophylaxis breakthrough, emphasizing the importance of accurate dose adjustment according to the latest eGFR and the need for novel, less toxic agents.

AB - Background: Rates and risk factors for cytomegalovirus (CMV) prophylaxis breakthrough and discontinuation were investigated, given uncertainty regarding optimal dosing for CMV primary (val)ganciclovir prophylaxis after solid organ transplantation (SOT).Methods: Recipients transplanted from 2012 to 2016 and initiated on primary prophylaxis were followed until 90 days post-transplantation. A (val)ganciclovir prophylaxis score for each patient per day was calculated during the follow-up time (FUT; score of 100 corresponding to manufacturers' recommended dose for a given estimated glomerular filtration rate [eGFR]). Cox models were used to estimate hazard ratios (HRs), adjusted for relevant risk factors.Results: Of 585 SOTs (311 kidney, 117 liver, 106 lung, 51 heart) included, 38/585 (6.5%) experienced prophylaxis breakthrough and 35/585 (6.0%) discontinued prophylaxis for other reasons. CMV IgG donor+/receipient- mismatch (adjusted HR [aHR], 5.37; 95% confidence interval [CI], 2.63 to 10.98; P < 0.001) and increasing % FUT with a prophylaxis score <90 (aHR, 1.16; 95% CI, 1.04 to 1.29; P = .01 per 10% longer FUT w/ score <90) were associated with an increased risk of breakthrough. Lung recipients were at a significantly increased risk of premature prophylaxis discontinuation (aHR, 20.2 vs kidney; 95% CI, 3.34 to 121.9; P = .001), mainly due to liver or myelotoxicity.Conclusions: Recipients of eGFR-adjusted prophylaxis doses below those recommended by manufacturers were at an increased risk of prophylaxis breakthrough, emphasizing the importance of accurate dose adjustment according to the latest eGFR and the need for novel, less toxic agents.

KW - CMV

KW - Cytomegalovirus

KW - Ganciclovir

KW - Prophylaxis

KW - SOT

KW - Transplantation

KW - Valganciclovir

U2 - 10.1093/ofid/ofz215

DO - 10.1093/ofid/ofz215

M3 - Journal article

VL - 6

SP - ofz215

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

SN - 2328-8957

IS - 6

ER -

ID: 57664679