Antiviral drug resistance in cytomegalovirus complicating hematopoietic stem cell transplantation: prevalence, genotypic analysis and novel UL97/UL54 variants.

IF 2.1 4区 医学 Q3 INFECTIOUS DISEASES
Journal of Chemotherapy Pub Date : 2026-10-01 Epub Date: 2026-03-15 DOI:10.1080/1120009X.2026.2643053
Şerife Çevik, Selma Gökahmetoğlu, Ömür Mustafa Parkan, Leylagül Kaynar, Musa Karakükçü, Mariam Kabirun
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引用次数: 0

Abstract

This study investigated antiviral resistance by sequencing UL97 and UL54 in cytomegalovirus (CMV) strains from haematology and hematopoietic stem cell transplant (HSCT) patients. Fifty-one samples from 48 patients (21 paediatric and 27 adult) with CMV DNA ≥1000 IU/mL and persistent viremia despite therapy were analysed. Resistance-associated mutations were identified in 6/48 patients (12.5%), all HSCT recipients - three paediatric and three adults. Detected mutations included UL97 (A591V, E596G and C603W), combined UL97 (M460I and C592G) and UL54 (F412L) mutations, and a UL54 (L957F) mutation. Additionally, 28 patients harboured 11 previously reported variants not associated with resistance. Novel UL97 (n = 18) and UL54 (n = 20) variants were also identified. In conclusion, prevalence of CMV antiviral resistance was 14.2% in CMV-infected HSCT recipients, slightly higher in paediatric patients. Detection of known and novel UL97/UL54 mutations highlights the importance of monitoring and the need for studies to assess the clinical impact of novel variants.

巨细胞病毒并发造血干细胞移植的抗病毒耐药性:患病率、基因型分析和新的UL97/UL54变异
本研究通过对来自血液学和造血干细胞移植(HSCT)患者的巨细胞病毒(CMV)毒株UL97和UL54进行测序,研究其抗病毒耐药性。分析了48例CMV DNA≥1000 IU/mL且经治疗后仍存在病毒血症的患者(21例儿童和27例成人)的51份样本。在6/48例(12.5%)HSCT受者(3名儿童和3名成人)中鉴定出耐药性相关突变。检测到的突变包括UL97 (A591V、E596G和C603W)、UL97 (M460I和C592G)和UL54 (F412L)联合突变以及UL54 (L957F)突变。此外,28名患者携带了11种先前报道的与耐药性无关的变异。新的UL97 (n = 18)和UL54 (n = 20)变异也被发现。总之,CMV感染的HSCT受者的CMV抗病毒药物耐药性患病率为14.2%,在儿科患者中略高。已知和新型UL97/UL54突变的检测突出了监测的重要性和研究评估新型变异临床影响的必要性。
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来源期刊
Journal of Chemotherapy
Journal of Chemotherapy 医学-药学
CiteScore
3.70
自引率
0.00%
发文量
144
审稿时长
6-12 weeks
期刊介绍: The Journal of Chemotherapy is an international multidisciplinary journal committed to the rapid publication of high quality, peer-reviewed, original research on all aspects of antimicrobial and antitumor chemotherapy. The Journal publishes original experimental and clinical research articles, state-of-the-art reviews, brief communications and letters on all aspects of chemotherapy, providing coverage of the pathogenesis, diagnosis, treatment, and control of infection, as well as the use of anticancer and immunomodulating drugs. Specific areas of focus include, but are not limited to: · Antibacterial, antiviral, antifungal, antiparasitic, and antiprotozoal agents; · Anticancer classical and targeted chemotherapeutic agents, biological agents, hormonal drugs, immunomodulatory drugs, cell therapy and gene therapy; · Pharmacokinetic and pharmacodynamic properties of antimicrobial and anticancer agents; · The efficacy, safety and toxicology profiles of antimicrobial and anticancer drugs; · Drug interactions in single or combined applications; · Drug resistance to antimicrobial and anticancer drugs; · Research and development of novel antimicrobial and anticancer drugs, including preclinical, translational and clinical research; · Biomarkers of sensitivity and/or resistance for antimicrobial and anticancer drugs; · Pharmacogenetics and pharmacogenomics; · Precision medicine in infectious disease therapy and in cancer therapy; · Pharmacoeconomics of antimicrobial and anticancer therapies and the implications to patients, health services, and the pharmaceutical industry.
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