Isada C M, Yen-Lieberman B, Lurain N S, Schilz R, Kohn D, Longworth D L, Taege A J, Mossad S B, Maurer J, Flechner S M, Mawhorter S D, Braun W, Gordon S M, Schmitt S K, Goldman M, Long J, Haug M, Avery R K
Department of Infectious Diseases, Cleveland Clinic Foundation, Cleveland, Ohio, USA.
Transpl Infect Dis. 2002 Dec;4(4):189-94. doi: 10.1034/j.1399-3062.2002.t01-1-02008.x.
Ganciclovir-resistant (GCV-R) cytomegalovirus (CMV) is now being reported with increasing frequency in solid organ transplant recipients.
To describe the clinical characteristics and outcomes of all solid organ transplant patients with GCV-R CMV seen between 1990 and 2000 at a single center.
Patients with clinically suspected GCV resistance had viral isolates subjected to phenotypic analysis by plaque reduction assay, and also genotypic analysis. Medical records of the 13 patients with GCV-R CMV were reviewed for demographic, microbiologic, clinical, and pathologic data.
Thirteen patients were identified, including 5 kidney, 1 heart, and 7 lung transplant recipients. All but one patient (92%) were CMV donor seropositive, recipient negative (D+/R-), and 11/13 (85%) had tissue-invasive CMV. CMV viremia was recurrent in 9/13 (69%); in 2 others, the first CMV episode was fatal. Overall, 9/13 (69%) of patients have died, all of CMV or its complications. Of the 10 who received foscarnet, only one survived. All patients had received GCV-based prophylactic regimens; 8/13 patients (62%) had received CMV hyperimmune globulin (CMVIG) as part of prophylaxis, 6/13 (46%) had received oral ganciclovir, and 5/13 (38%) had received intermittent (3 x/week) IV ganciclovir for prophylaxis.
GCV-R CMV is associated with CMV D+/R- status, tissue-invasive disease, and high mortality even with foscarnet therapy. Exposure to less than fully therapeutic levels of GCV, in the form of oral or intermittent IV GCV, is common. The use of CMVIG in prophylaxis does not appear to prevent resistance. Further work remains to be done to elucidate the risk factors and optimal mode of prophylaxis and treatment for GCV-R CMV.
耐更昔洛韦（GCV-R）的巨细胞病毒（CMV）在实体器官移植受者中的报道频率日益增加。
描述1990年至2000年间在单一中心就诊的所有患有GCV-R CMV的实体器官移植患者的临床特征及转归。
临床怀疑GCV耐药的患者，其病毒分离株通过蚀斑减少试验进行表型分析，并进行基因型分析。回顾了13例GCV-R CMV患者的病历，以获取人口统计学、微生物学、临床和病理学数据。
共识别出13例患者，包括5例肾移植受者、1例心脏移植受者和7例肺移植受者。除1例患者外（92%），所有患者均为CMV供体血清学阳性、受体血清学阴性（D+/R-），且11/13（85%）患有组织侵袭性CMV。9/13（69%）的患者CMV病毒血症复发；另外2例患者中，首次CMV发作是致命的。总体而言，9/13（69%）的患者死亡，均死于CMV或其并发症。在接受膦甲酸钠治疗的10例患者中，仅1例存活。所有患者均接受了基于GCV的预防方案；8/13例患者（62%）接受了CMV高效价免疫球蛋白（CMVIG）作为预防措施的一部分，6/13（46%）接受了口服更昔洛韦，5/13（38%）接受了间歇性（每周3次）静脉注射更昔洛韦进行预防。
GCV-R CMV与CMV D+/R-状态、组织侵袭性疾病相关，即使采用膦甲酸钠治疗，死亡率也很高。以口服或间歇性静脉注射GCV形式暴露于未达到完全治疗水平的情况很常见。预防性使用CMVIG似乎无法预防耐药。仍需进一步开展工作以阐明GCV-R CMV的危险因素以及预防和治疗的最佳模式。
