Li Fanny, Kenyon Kenneth W, Kirby Katharine A, Fishbein Daniel P, Boeckh Michael, Limaye Ajit P
Department of Pharmacy Services, University of Washington, Seattle, WA 98195, USA.
Clin Infect Dis. 2007 Aug 15;45(4):439-47. doi: 10.1086/519941. Epub 2007 Jul 10.
The incidence and clinical and virologic aspects of ganciclovir-resistant cytomegalovirus (CMV) disease have not been well-characterized in heart transplant recipients.
We retrospectively analyzed all patients who underwent their first heart transplantation during the period from 1 January 1995 through 30 June 2005 at a single health care center. Cox proportional hazard regression was used to assess the relationship between clinical variables and CMV disease. Portions of the UL97 gene were sequenced in patients with slow clinical and/or virologic response to ganciclovir therapy.
Cytomegalovirus disease developed in 32 (11.7%) of 274 patients at a median of 4.2 months after transplantation (range, 1.8-11.6 months after transplantation) and was independently associated with donor-seropositive/recipient-seronegative (D+/R-) serostatus (adjusted hazard ratio, 6.93; P<.001). The incidence of ganciclovir-resistant CMV disease was 1.5% overall (4 of 274 patients), 5% among D+/R- serostatus recipients (4 of 80 patients), and 12.5% among patients who developed CMV disease (4 of 32 patients). Ganciclovir-resistant CMV disease was significantly associated with D+/R- serostatus (4 [5%] of 80 vs. 0 [0%] of 153 patients; P=.02), greater prior exposure to ganciclovir (median duration of exposure, 150 vs. 69 days; P=.003), and substantial morbidity, including prolonged CMV-associated hospitalization (median duration of hospitalization, 66 vs. 0 days; P<.01).
CMV disease, including ganciclovir-resistant disease, is an important clinical problem in D+/R- heart transplant recipients who receive antiviral prophylaxis. Strategies specifically designed to reduce the incidence and impact of CMV disease in this population are warranted.
在心脏移植受者中,耐更昔洛韦的巨细胞病毒(CMV)疾病的发病率、临床及病毒学特征尚未得到充分描述。
我们回顾性分析了1995年1月1日至2005年6月30日期间在单一医疗中心接受首次心脏移植的所有患者。采用Cox比例风险回归分析评估临床变量与CMV疾病之间的关系。对更昔洛韦治疗临床和/或病毒学反应缓慢的患者,对其UL97基因部分进行测序。
274例患者中有32例(11.7%)发生CMV疾病,发生时间中位数为移植后4.2个月(范围为移植后1.8 - 11.6个月),且与供体血清学阳性/受体血清学阴性(D+/R-)血清状态独立相关(校正风险比为6.93;P<0.001)。耐更昔洛韦的CMV疾病总体发病率为1.5%(274例患者中的4例),在D+/R-血清状态的受者中为5%(80例患者中的4例),在发生CMV疾病的患者中为12.5%(32例患者中的4例)。耐更昔洛韦的CMV疾病与D+/R-血清状态显著相关(80例中的4例[5%] vs. 153例中的0例[0%];P = 0.02),既往更昔洛韦暴露时间更长(暴露时间中位数为150天 vs. 69天;P = 0.003),以及包括CMV相关住院时间延长在内的严重发病率(住院时间中位数为66天 vs. 0天;P<0.01)。
CMV疾病,包括耐更昔洛韦的疾病,是接受抗病毒预防的D+/R-心脏移植受者中的一个重要临床问题。有必要制定专门策略以降低该人群中CMV疾病的发病率和影响。