Oral Valganciclovir Is Noninferior to Intravenous Ganciclovir for the Treatment of Cytomegalovirus Disease in Solid Organ Transplant Recipients

Intravenous ganciclovir is the standard treatment for cytomegalovirus disease in solid organ transplant recipients. Oral valganciclovir is a more convenient alternative. In a randomized, international trial, recipients with cytomegalovirus disease were treated with either 900 mg oral valganciclovir or 5 mg/kg i.v. ganciclovir twice daily for 21 days, followed by 900 mg daily valganciclovir for 28 days. A total of 321 patients were evaluated (valganciclovir [n = 164]; i.v. ganciclovir [n = 157]). The success rate of viremia eradication at Day 21 was 45.1% for valganciclovir and 48.4% for ganciclovir (95% CI -14.0% to +8.0%), and at Day 49; 67.1% and 70.1%, respectively (p = NS). Treatment success, as assessed by investigators, was 77.4% versus 80.3% at Day 21 and 85.4% versus 84.1% at Day 49 (p = NS). Baseline viral loads were not different between groups and decreased exponentially with similar half-lives and median time to eradication (21 vs. 19 days, p = 0.076). Side-effects and discontinuations of assigned treatment (18 of 321 patients) were comparable. Oral valganciclovir shows comparable safety and is not inferior to i.v. ganciclovir for treatment of cytomegalovirus disease in organ transplant recipients and provides a simpler treatment strategy, but care should be taken in extrapolating to organ transplant recipients not properly represented in the present study.     

人巨细胞病毒被膜磷蛋白pp65的检测及其在肾移植的临床应用

目的建立一种快速、简便诊断肾移植受者人巨细胞病毒（human cytomegalovirus,HCMV）活动性感染的方法。方法运用免疫组织化学的催化信号扩增法检测外周血白细胞中的人巨细胞病毒磷蛋白（phosphoprotein,pp65）,并与抗HCMV-IgM检测法、巨细胞病毒信使核糖核酸（pp67-mRNA）检测法作比较。结果检测53例肾移植受者中,HCMVpp65抗原阳性26例,IgM抗体阳性17例,pp67-mRNA检测阳性27例,pp65抗原阳性细胞指数为（71±45）个／2×10^5个白细胞（WBC）,而有症状的CMV病16例,抗原阳性细胞指数为（83±46）个／2×10^5个WBC。pp65的敏感性、特异性、阳性预测值与阴性预测值分别是100％、73．0％、61．5％和100％。结论该法敏感,简便,可作为肾移植术后HCMV病的早期诊断,并可指导抗病毒治疗。     

病理性黄疸新生儿巨细胞病毒感染的临床研究

目的 分析病理性黄疸患儿巨细胞病毒(CMV)感染情况,探讨母乳CMV-DNA检测的临床意义。方法 选取庆阳市人民医院住院的病理性黄疸新生儿300例,用FQ-PCR方法检测患儿血浆、外周血单个核细胞(PBMC)、尿液和母乳的CMV-DNA,ELISA法检测患儿血清CMV-IgM和IgG,分析CMV感染患儿的临床数据。结果 300例病理性黄疸新生儿中,CMV感染的阳性率为13.33%(40例),其中患儿血清CMV-IgM阳性率为4.33%(13例),CMV-IgG阳性率为80.85%(228例)。母乳CMV-DNA阳性率为46.00%(138例),患儿血浆CMV-DNA阳性率为4.00%(12例),PBMC CMV-DNA阳性率为6.67%(20例),患儿尿液CMV-DNA阳性率为10.00%(30例)。患儿尿液CMV-DNA的阳性率与乳汁CMV-DNA的阳性率有显著相关性(P<0.01)。40例CMV感染患儿中,婴儿肝炎综合症为13例(32.50%),新生儿肺炎12例(30.00%),缺血缺氧性脑病6例(15.00%),听力损伤5例(12.50%),腹股沟斜疝2例(5.00%)。结论 CMV感染是新生儿病理性黄疸主要原因之一;检测产妇母乳中CMV-DNA对母乳喂养具有临床指导意义,有助于预防CMV感染。     

Clinical Utility of Cytomegalovirus Viral Load Testing for Predicting CMV Disease in D+/R- Solid Organ Transplant Recipients

Despite prophylaxis, cytomegalovirus (CMV) disease is common in donor seropositive (D+)/recipient seronegative (R-) transplant patients after cessation of prophylaxis. Early detection of CMV may allow for pre-emptive therapy to prevent active disease. The clinical utility of quantitative plasma viral load measurements for predicting CMV disease was determined in 364 D+/R- organ transplant patients receiving prophylaxis (100 d of valganciclovir or oral ganciclovir). Measurements were performed every 2 weeks until day 100 and at months 4, 4.5, 5, 6, 8 and 12 post-transplant. CMV disease occurred in 64 (17.6%) patients by 12 months. Using a positive cut-off value of >400 copies/mL, sensitivity was 38%, specificity 60%, positive predictive value 17%, and negative predictive value 82% for prediction of CMV disease. Therefore, routine monitoring would have predicted disease in only 24/64 (38%) patients. The test characteristics were not improved by changing the viral load cut-off point for defining a positive result. Similarly, single time point measures at the end of prophylaxis or month 4 had low sensitivity for disease prediction. Overall, regular CMV plasma viral load measurements were only of modest value in predicting CMV disease.     

肾移植术后肺炎48例诊治分析

目的总结肾移植术后肺炎的诊治经验。方法回顾性分析48例肾移植术后肺炎患者的临床资料。结果 48例肾移植术后肺炎患者的发病时间为术后7d～2年3个月,其中术后1～4个月发病占75%(36/48)。重症肺炎12例(25%),4例(8%)在发病后迅速发展为急性呼吸窘迫综合征(ARDS)。肺炎患者早期临床症状不突出,发热是最早或主要表现,有时是唯一的表现,部分病例有干咳、咯黄白色黏液痰,混合细菌或真菌感染时痰量增多。肺部体征多不明显。移植3个月内以巨细胞病毒(CMV)肺炎为主,并常混合其他微生物感染,3个月后以细菌感染为主。影像学检查结果主要表现为间质性肺炎。2007年6月至2008年6月发生感染的患者,只给予麦考酚吗乙酯(MMF)或钙调磷酸酶抑制剂(CNI)减量。2008年6月以后,诊断肺部感染的患者,确诊后完全停用MMF和CNI减量。3例患者使用免疫球蛋白500mg/(kg.d)。酌情使用甲泼尼龙20mg或40mg,每日2次。在无确切临床病原学资料时,给予广谱抗生素、抗病毒联合治疗。病原学明确后,给予针对性抗感染治疗。43例(90%)治疗有效,3例转外院,1例并发脑出血放弃治疗,1例死于急性呼吸衰竭。结论肾移植受者肺炎起病大多隐匿,病程进展快。病原体以CMV和细菌为主,多表现为多重感染及重症肺炎。肾移植术后第1～4个月是肺炎发生和死亡的危险时期。及时调整机体免疫抑制状态,明确肺部感染的病原体,采用针对性抗感染治疗,有助于提高肾移植术后肺炎治愈率和降低病死率。     

Cytomegalovirus Disease in High-Risk Transplant Recipients Despite Ganciclovir or Valganciclovir Prophylaxis

The clinical patterns and predictors of cytomegalovirus (CMV) disease in kidney and/or pancreas transplant patients on ganciclovir (1.0 g po t.i.d.) or valganciclovir (450 mg po q.d.) prophylaxis were studied. This is a retrospective analysis of 129 transplant recipients. Median follow up was 12 months (range, 6-18 months). The overall incidence of CMV disease at 1-year post-transplant was 14% (4% tissue-invasive, 10% noninvasive). Seventeen of 18 patients were diagnosed with CMV after completion of 3 months' prophylaxis (median 8 weeks, range, 2-28 weeks). Induction treatment with thymoglobulin, and Donor +/Recipient - CMV status were the strongest predictors for the development of CMV disease. Cytomegalovirus incidence was not different between patients treated with ganciclovir or valganciclovir (15 vs. 17%, respectively). Valganciclovir (450 mg q.d.) is as effective as oral ganciclovir in CMV prophylaxis. High-risk individuals might require higher doses or longer duration of valganciclovir treatment.     

Increased risk of PTLD in lung transplant recipients with cystic fibrosis

Background

Post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following lung transplantation. Recipients with cystic fibrosis (CF) may have an increased risk of PTLD although the literature is limited to single center cohorts. Our primary aim is to examine PTLD in an adult lung transplant population by utilizing the International Society for Heart and Lung Transplantation Registry.

Human herpes viruses in burn patients: A systematic review

Objective

The contribution of human herpes viruses, including herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV) to morbidity and mortality after burns remains controversial. This systematic review was undertaken to assess evidence of herpes virus-related morbidity and mortality in burns.

巨细胞病毒感染对肾移植受者的影响及其危险因素分析

目的 探讨巨细胞病毒（CMV）感染对肾移植受者的影响以及引起巨细胞病毒感染的危险因素。 方法 回顾性分析2000年1月至2004年12月892例肾移植的资料。按术后是否有巨细胞病毒感染分为病例组和对照组。应用Log-Rank检验比较两组1、3、5年人和肾存活率的差异；比较两组术后各种并发症发病率以及应用免疫抑制剂和抗病毒药物的差异。应用Logistic回归分析探讨巨细胞病毒感染的独立影响因素。 结果 病例组1、3、5年人存活率分别为81.3％、72.8％和54.8％，而对照组分别为96.4％、91.4％和79.9％，前者显著低于后者（Log-Rank值＝49.62，P < 0.01）。病例组1、3、5年移植肾存活率分别为71.0％、66.2％和46.1%，而对照组分别为91.5％、86.6％和74.5％，两者差异也有统计学意义（Log-Rank值44.87，P < 0.01）。病例组急性排斥发生率为24.9%，对照组为13.9%，前者显著高于后者（χ2＝14.49，P < 0.01）。Logistic回归分析表明，急性排斥、霉酚酸酯用量>2 g、应用抗胸腺细胞球蛋白（ATG）、抗淋巴细胞球蛋白（ALG）或OKT3是巨细胞感染的独立危险因素（OR值分别为1.464、3.097和2.837，P < 0.05)；应用更昔洛韦是巨细胞病毒感染的保护因素(OR值为0.234，P < 0.01)。 结论 巨细胞病毒感染显著降低了肾移植长期人和肾存活率。急性排斥、霉酚酸酯用量过大和应用抗淋巴细胞抗体是引起巨细胞病毒感染的独立危险因素。术后预防性应用更昔洛韦，可以有效减少巨细胞病毒感染。     

优先治疗和普遍预防两种方案在肾移植术后巨细胞病毒感染中的疗效比较

目的 对比分析优先治疗和普遍预防两种方案在预防和治疗肾移植术后巨细胞病毒(CMV)感染中的疗效.方法 将64例肾移植受者随机分为优先治疗组(31例)和普遍预防组(33例).两组受者肾移植术后均接受14 d预防CMV感染的基础治疗(静脉滴注更昔洛韦250 mg/d).随后,普遍预防组受者继续口服更昔洛韦至术后90 d.优先治疗组中的高危受者继续口服更昔洛韦,直至术后90d;中危受者中仅CMV pp65抗原阳性受者静脉滴注更昔洛韦,至CMV pp65抗原转阴后停药,低危受者在基础治疗后不再使用更昔洛韦.研究期为6个月,此期间监测两组受者血清CMV pp65抗原和CMV DNA,以及血常规、尿常规、肝功能、肾功能和排斥反应发生情况.结果 普遍预防组15例(45.5%)出现CMV抗原血症,有5例(15.2%)的CMV DNA负荷量持续升高,其中3例(9.1%)发展成为CMV病.优先治疗组13例(41.9%)出现CMV抗原血症,有4例(12.9%)的CMV DNA负荷量持续升高,其中2例(6.5%)发展为CMV病.普遍预防组和优先治疗组急性排斥反应发生率分别为9.1%(3/33)和9.7%(3/31);其他感染总的发生率分别为15.2%(5/33)和19.4%(6/31),差异均无统计学意义(P>0.05).两组受者移植6个月时的存活率分别为97%和100%,其血肌酐的差异也无统计学意义(P>0.05).结论 根据受者CMV感染的风险状态采取优先治疗方案能有效预防和治疗肾移植术后CMV感染,其效果与普遍预防方案相当.