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Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants
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Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants
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Journal Article
Emergence of ganciclovir-resistant cytomegalovirus disease among recipients of solid-organ transplants
2000
Overview
Concerns have been raised about emergence of ganciclovir resistance as a result of the advent of both routine oral ganciclovir prophylaxis and highly potent immuno-suppression. We retrospectively assessed the occurrence of ganciclovir-resistant cytomegalovirus disease among transplant recipients who had received oral ganciclovir prophylaxis and highly potent immunosuppression.
We studied 240 recipients of liver, kidney, or pancreas transplants. Antiviral susceptibility testing of blood cytomegaloviral isolates was done when patients failed to respond to intravenous ganciclovir treatment for symptomatic cytomegalovirus infection. Portions of the
UL97 gene associated with ganciclovir resistance were sequenced in cytomegalovirus isolates with phenotypic resistance to ganciclovir.
Ganciclovir-resistant cytomegalovirus disease developed in five (7%) of 67 seronegative recipients of cytomegalovirus-seropositive organs (D+/R−) compared with none of 173 seropositive recipients (p=0·002). Among the 25 (10·4%) patients who developed cytomegalovirus disease within 1 year after transplantation, five had ganciclovir-resistant cytomegalovirus disease. Among D+/R− transplant recipients, ganciclovir-resistant cytomegalovirus disease was more common among the group receiving the most potent immunosuppression—ie, recipients of kidney and pancreas or pancreas alone (four of 19) compared with all other transplant recipients (one of 48, p=0·02). Ganciclovir-resistant cytomegalovirus disease was diagnosed at a median of 10 months after transplantation (range 7–12) after lengthened exposure to ganciclovir, was associated with previously described mutations of the
UL97 gene, and led to serious clinical complications.
Ganciclovir-resistant cytomegalovirus is an important cause of late morbidity among D+/R− transplant recipients who have had lengthened exposure to ganciclovir and have received highly potent immunosuppression. Strategies to reduce this complication, especially among D+/R− patients, are warranted.
Publisher
Elsevier Ltd,Lancet,Elsevier Limited
Subject
/ Aged
/ Antibiotics. Antiinfectious agents. Antiparasitic agents
/ Antiviral Agents - therapeutic use
/ Biological and medical sciences
/ Cytomegalovirus - drug effects
/ Cytomegalovirus - isolation & purification
/ Cytomegalovirus Infections - drug therapy
/ Cytomegalovirus Infections - epidemiology
/ Disease
/ Drug Resistance, Microbial - genetics
/ Female
/ Ganciclovir - therapeutic use
/ Humans
/ Immunosuppression - adverse effects
/ Kidney Transplantation - adverse effects
/ Kidneys
/ Liver Transplantation - adverse effects
/ Male
/ Opportunistic Infections - epidemiology
/ Opportunistic Infections - virology
/ Organ Transplantation - adverse effects
/ Pancreas Transplantation - adverse effects
/ Pharmacology. Drug treatments
