Intra-host diversity of drug-resistant cytomegalovirus: A case report of cytomegalovirus infection after allogeneic hematopoietic cell transplantation.

Abstract

Cytomegalovirus (CMV) is a major infectious agent causing severe complications in allogeneic hematopoietic cell transplantation (HCT) recipients, thereby warranting the need for aggressive preemptive or targeted antiviral therapy. However, prolonged or repeated use of antiviral agents, such as ganciclovir (GCV), foscarnet (FOS), and cidofovir (CDV), can result in drug-resistant CMV infection, posing challenges to successful outcomes. Here, we report a case of a patient with acute myeloid leukemia and drug-resistant CMV infection who presented with persistent CMV DNAemia, colitis, pneumonia, and encephalitis. An intra-host diversity of UL97 and UL54 mutations were detected through the genotypic resistance testing conducted on two blood samples (D+199 and D+224) and a cerebrospinal fluid (CSF) specimen (D+260) collected from the patient. UL97 L595W/L595F and L595W mutations were detected in the blood and CSF samples, respectively, that conferred GCV resistance. UL54 F412L mutation detected in all three samples conferred GCV/CDV resistance. However, the V787L mutation of UL54, conferring GCV/FOS resistance, was observed only in the D+224 blood sample. Despite combination therapy with FOS and high dose GCV and adjunctive therapy with leflunomide, the patient died from CMV infection and multiple organ failure on D+279. Further data on resistant mutations and intra-host diversity of CMV should be accumulated to elucidate the antiviral resistance and related outcomes.

• Authors: Ji-Yoon Jung, Dukhee Nho, Sung-Yeon Cho, Dong-Gun Lee, Su-Mi Choi, Hee-Je Kim, Myungshin Kim, Eun-Jee Oh
• Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy (J Infect Chemother) Vol. 28 Issue 10 Pg. 1415-1418 (Oct 2022) ISSN: 1437-7780 [Electronic] Netherlands
• PMID: 35810104 (Publication Type: Case Reports, Journal Article)
• Copyright: Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Antiviral Agents
• Foscarnet
• Phosphotransferases (Alcohol Group Acceptor)
• Cidofovir
• Ganciclovir

Topics

• Antiviral Agents (pharmacology, therapeutic use)
• Cidofovir (therapeutic use)
• Cytomegalovirus (genetics)
• Cytomegalovirus Infections (drug therapy)
• Drug Resistance, Viral (genetics)
• Foscarnet (therapeutic use)
• Ganciclovir (pharmacology, therapeutic use)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Mutation
• Phosphotransferases (Alcohol Group Acceptor) (genetics, therapeutic use)