Wiita A P, Roubinian N, Khan Y, Chin-Hong P V, Singer J P, Golden J A, Miller S
Department of Laboratory Medicine, University of California, San Francisco, California 94107, USA.
Transpl Infect Dis. 2012 Jun;14(3):248-58. doi: 10.1111/j.1399-3062.2012.00723.x. Epub 2012 Mar 5.
The optimal method of both predicting and preventing cytomegalovirus (CMV) disease in lung transplant recipients remains unclear. In particular, the most appropriate duration of CMV prophylaxis post transplant is unresolved. We report herein our experience with a planned indefinite regimen of valganciclovir prophylaxis and monitoring of quantitative CMV load in bronchoalveolar lavage (BAL) fluid.
We performed a single-center observational study with both prospective and retrospective components. The included patients (n = 128) received a planned regimen of indefinite valganciclovir prophylaxis post transplant, regardless of donor (D)/recipient (R) CMV serostatus. Real-time polymerase chain reaction assay for detection of CMV in BAL was prospectively performed over a 1-year period. Clinical data were reviewed retrospectively; median follow-up was 24.8 months (range 1-93 months).
Sixty-five patients (50.6%) discontinued valganciclovir prophylaxis, either temporarily or permanently, with a primary cause of mild leukopenia. Six cases of CMV disease were identified (4.7%), with no significant difference between those who were on continuous prophylaxis or not (4.6% vs. 4.9%; P = non-significant [ns]). However, those who discontinued prophylaxis showed an increased incidence of laboratory-detected CMV infection (40.7% vs. 12.7%; P = 0.001). High-risk D+/R- patients did not demonstrate a significantly increased incidence of CMV disease (8.1% vs. 3.3% other serotypes; P = ns). Three patients (2.3%) developed valganciclovir-resistant CMV disease. Molecular detection of CMV in BAL fluid was significantly more sensitive than shell vial culture. However, BAL CMV viral load was not predictive of subsequent disease development.
Extended valganciclovir prophylaxis for all lung transplant recipients led to a low incidence of CMV disease and resistance. In such low-incidence populations, routine quantitation of CMV in BAL did not confer significant clinical benefit over non-quantitative methods in prediction of CMV disease onset.
预测和预防肺移植受者巨细胞病毒（CMV）疾病的最佳方法仍不明确。特别是，移植后CMV预防的最合适持续时间尚未解决。我们在此报告我们使用缬更昔洛韦进行计划性无限期预防方案以及监测支气管肺泡灌洗（BAL）液中CMV定量载量的经验。
我们进行了一项包含前瞻性和回顾性成分的单中心观察性研究。纳入的患者（n = 128）移植后接受计划性无限期缬更昔洛韦预防方案，无论供体（D）/受体（R）CMV血清学状态如何。在1年期间前瞻性地进行实时聚合酶链反应检测BAL中的CMV。回顾性审查临床数据；中位随访时间为24.8个月（范围1 - 93个月）。
65例患者（50.6%）暂时或永久停用缬更昔洛韦预防，主要原因是轻度白细胞减少。确定了6例CMV疾病（4.7%），持续预防和未持续预防的患者之间无显著差异（4.6%对4.9%；P = 无显著差异[ns]）。然而，停用预防的患者实验室检测到的CMV感染发生率增加（40.7%对12.7%；P = 0.001）。高危D + /R - 患者的CMV疾病发生率未显著增加（8.1%对其他血清型的3.3%；P = ns）。3例患者（2.3%）发生了缬更昔洛韦耐药的CMV疾病。BAL液中CMV的分子检测比空斑试验培养显著更敏感。然而，BAL中CMV病毒载量不能预测随后的疾病发展。
对所有肺移植受者延长缬更昔洛韦预防导致CMV疾病和耐药的发生率较低。在这种低发病率人群中，BAL中CMV的常规定量在预测CMV疾病发作方面与非定量方法相比未带来显著的临床益处。
