Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients
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Risk Factors for Failure of Primary (Val)ganciclovir Prophylaxis Against Cytomegalovirus Infection and Disease in Solid Organ Transplant Recipients. / Khurana, Mark P; Lodding, Isabelle P; Mocroft, Amanda; Sørensen, Søren S; Perch, Michael; Rasmussen, Allan; Gustafsson, Finn; Lundgren, Jens D.
In: Open Forum Infectious Diseases, Vol. 6, No. 6, ofz215, 2019.Research output: Contribution to journal › Journal article › Research › peer-review
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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
Y1 - 2019
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.
U2 - 10.1093/ofid/ofz215
DO - 10.1093/ofid/ofz215
M3 - Journal article
C2 - 31211159
VL - 6
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
SN - 2328-8957
IS - 6
M1 - ofz215
ER -
ID: 237797333