Analysis and characterization of antiviral drug-resistant cytomegalovirus isolates from solid organ transplant recipients.
The development of cytomegalovirus (CMV) disease and subsequent emergence of drug-resistant strains was examined in a large group of solid organ transplant recipients; drug-resistant CMV was detected in a total of 30 transplant recipients (20 lung, 5 kidney, 4 heart, and 1 liver). Drug resistance was confirmed both phenotypically and genotypically. The sequences of drug-resistant CMV strains from the same patient differed from drug-susceptible baseline sequences only at single sites previously confirmed to confer drug resistance. At least 1 isolate from each patient had a mutation in the UL97 phosphotransferase coding sequence. Mutations in the DNA polymerase gene were found in 6 of 38 sequenced strains. Lung transplant recipients had the highest incidence of drug-resistant virus: of the 30 patients, 28 were CMV-seronegative transplant recipients of CMV-seropositive organs, which strongly supports the premise that drug resistance is most prevalent in that transplant population.
Lurain
Nell S
NS
Department of Immunology/Microbiology, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. nlurain@rush.edu
Bhorade
Sangeeta M
SM
Pursell
Kenneth J
KJ
Avery
Robin K
RK
Yeldandi
Vijay V
VV
Isada
Carlos M
CM
Robert
Emmanuel S
ES
Kohn
Debra J
DJ
Arens
Max Q
MQ
Garrity
Edward R
ER
Taege
Alan J
AJ
Mullen
Martin G
MG
Todd
Kathleen M
KM
Bremer
James W
JW
Yen-Lieberman
Belinda
B
D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000188:drug therapy / Q000821:virology*; D004279:DNA, Viral / Q000032:analysis; D024882:Drug Resistance, Viral / Q000235:genetics*; D005814:Genes, Viral / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D009154:Mutation; D016377:Organ Transplantation; D010641:Phenotype; D016133:Polymerase Chain Reaction
D000998:Antiviral Agents; D004279:DNA, Viral