Investigation of Ganciclovir Resistance in CMV UL54 and UL97 Gene Regions in lmmunocompromised Patients Receiving Gancyclovir Treatment


Delice S. , GÖKAHMETOĞLU S. , KAYNAR L. , KARAKÜKCÜ M.

MIKROBIYOLOJI BULTENI, cilt.49, ss.393-402, 2015 (SCI İndekslerine Giren Dergi) identifier

  • Cilt numarası: 49 Konu: 3
  • Basım Tarihi: 2015
  • Dergi Adı: MIKROBIYOLOJI BULTENI
  • Sayfa Sayıları: ss.393-402

Özet

Cytomegalovirus (CMV) is a main cause of severe morbidity and mortality in immunocompromised patients. Ganciclovir (GCV) is used for both prophylaxis and treatment of CMV disease with successful results, however GCV resistance has been increasingly reported. The aim of this study was to investigate the GCV resistance in patients whose viral loads did not decline VI 000 copies/mL) despite of receiving GCV treatment, by using sequence analysis method. A total of 30 patients, 25 of them were bone marrow transplant (BMT) and five who were followed in hematology clinics (non-Hodgkin lymphoma, lung cancer, diffuse large B cell lymphoma, combined immune deficiency, chronic lymphocytic leukemia) were included in the study. CMV-DNA levels were monitored by real-time polymerase chain reaction (QIAsymphony, Artus (R) CMV QS-RGQ kit, Qiagen, Germany), and DNA sequence analysis (ABI 310 Genetic Analyzer, Applied Biosystems, USA) was performed to detect the mutations leading to CMV antiviral drug resistance in following gene regions: 420-664 codons in UL97 gene region and 261 to 588 and 740 to 987 codons in UL54 gene region. Of 30 patients included, M460V mutation in CMV UL97 gene region was detected in one (3.3%) (1st case) and L802M mutation in UL54 gene region, in addition to P887S and S897L variant sequences in another patient (3.3%) (2nd case). The first patient was a 20-year-old male with acute myeloid leukemia who underwent BMT. The blood sample for the investigation of antiviral drug resistance was taken on the 117th day of transplantation (with simultaneous viral load 4470 copies/mL) and the patient has been using GCV for 70 days when the sample was taken. Valganciclovir (VGCV) and foscarnet (FOS) were used for the therapy of the first patient and monitored. The second patient was a 19-year-old male with acute lymphoblastic leukemia who underwent BMT. The blood sample for the investigation of antiviral drug resistance was taken on the 109th day of transplantation (with simultaneous viral load 4830 copies/mL) and the patient received GCV for 26 days and VGCV for 40 days when the sample was taken. FOS and cidofovir were used for the therapy of the second patient but the patient was lost due to the underlying diseases. In conclusion, mutations responsible for GCV resistance was detected in 6.6% (2/30) of immunocompromised patients receiving GCV, indicating that the determination of CMV antiviral drug resistance may help clinicians for planning the antiviral therapy.