Division of Infectious Diseases, Department of Medicine, Johns Hopkins, Baltimore, MD, USA.
Pueblo Infectious Diseases, PLLC, Pueblo, CO, USA.
Transpl Infect Dis. 2021 Jun;23(3):e13521. doi: 10.1111/tid.13521. Epub 2020 Dec 2.
Treatment of ganciclovir-resistant (GCV-R)/refractory cytomegalovirus (CMV) infections in blood/marrow transplant (BMT) and solid organ transplant (SOT) recipients remains suboptimal. Cidofovir (CDV), a nucleotide analogue with anti-CMV activity, is nephrotoxic and oculotoxic.
We retrospectively evaluated the outcomes of SOT and BMT patients with GCV-R/refractory CMV treated with CDV between 1/1/2008 and 12/31/2017.
baseline demographics, CMV serostatus, clinical and virologic presentations and outcomes, UL97 and UL54 genotype mutations, drug toxicities, and cause of death. Descriptive statistics were used.
16 patients received CDV for treatment of CMV: six BMT and 10 SOT. Seven (47%) of the patients had high-risk donor/recipient serostatus: six (60%) SOT were D+/R-; one (16.7%) BMT was D-/R+. Median time to CMV DNAemia was 131 days post-transplant (IQR, 37.5-230.3). Proven tissue invasive disease was present in three patients (18.8%). Twelve (75%) had genotype testing; 10 (83.3%) of those had antiviral resistance mutations. While on CDV, six (37.5%) developed nephrotoxicity, and four (25%) developed uveitis (two had both uveitis and nephrotoxicity). Eight (50%) had failure to clear CMV DNAemia despite CDV treatment. Eight (50%) of the patients died; median time to death, after initiation of CDV, was 33.5 days [IQR22-988].
In the absence of good therapeutic alternatives, CDV is used in GCV-R/refractory CMV infection. However, it is associated with a substantial risk of toxicity and failure to clear CMV DNAemia, highlighting the need for development of newer and less toxic therapies. The high mortality in this group of patients underscores the severity of illness in this population.
造血干细胞移植（BMT）和实体器官移植（SOT）受者中更昔洛韦耐药（GCV-R）/难治性巨细胞病毒（CMV）感染的治疗仍不尽人意。西多福韦（CDV）是一种具有抗 CMV 活性的核苷酸类似物，具有肾毒性和眼毒性。
我们回顾性评估了 2008 年 1 月 1 日至 2017 年 12 月 31 日期间接受 CDV 治疗的 GCV-R/难治性 CMV 感染的 SOT 和 BMT 患者的结局。
基线人口统计学、CMV 血清状态、临床和病毒学表现和结局、UL97 和 UL54 基因型突变、药物毒性和死亡原因。采用描述性统计。
16 例患者接受 CDV 治疗 CMV：6 例 BMT 和 10 例 SOT。7 例（47%）患者具有高危供体/受体血清状态：6 例（60%）SOT 为 D+/R-；1 例（16.7%）BMT 为 D-/R+。移植后 131 天（IQR，37.5-230.3）中位时间出现 CMV DNA 血症。3 例（18.8%）患者存在明确的组织侵袭性疾病。12 例（75%）进行了基因型检测；10 例（83.3%）存在抗病毒耐药突变。在接受 CDV 治疗期间，6 例（37.5%）发生肾毒性，4 例（25%）发生虹膜炎（2 例同时发生虹膜炎和肾毒性）。8 例（50%）尽管接受 CDV 治疗，但 CMV DNA 血症仍未清除。8 例（50%）患者死亡；CDV 治疗开始后中位死亡时间为 33.5 天[IQR22-988]。
在缺乏良好治疗选择的情况下，CDV 用于 GCV-R/难治性 CMV 感染。然而，它与毒性和 CMV DNA 血症清除失败的风险显著相关，突出了开发新型、毒性较小的治疗方法的必要性。该组患者的高死亡率突出了该人群疾病的严重程度。
