Transp Infect Dis：抗病毒药物的耐药性或更易于发生在囊性纤维化患者机体中

  一种名为更昔洛韦的药物常用于肺部移植患者，作用是保护患者免于受到移植后致死性病毒的感染；对34名患者研究发现，更昔洛韦可以降低3%-6%的患者死亡率，但有5%-10%患者机体中的病毒对更昔洛韦产生耐药性。

  近日，刊登在国际杂志Transplant Infectious Disease上的一篇研究论文中，来自芝加哥罗耀拉大学医学中心(Loyola University Medical Center)的研究人员通过研究发现，这种耐药性或许在囊性纤维化患者机体中更为频繁，这些患者机体血液中更昔洛韦的水平并不充足，这就使得病人机体的病毒更易于复制，进而增加病毒突变的发生以及药物耐受性的产生。 研究者James Gagermeier博士表示，囊性纤维化病人需要被监护来确保其机体中更昔洛韦的治疗水平，文章中我们记录了51名肺部移植患者的医疗记录，其中21名病人为巨细胞病毒感染患者，这些感染者中有10名患者对更昔洛韦反应较好，这就意味着病毒在患者机体中14天内都可以被消灭；在剩下的11名患者中，6名更昔洛韦水平充足的病人发生了延迟，但其对药物并无反应，5名患者机体中更昔洛韦水平不足的患者对药物不能产生反应，这5名患者均产生了耐药性的巨细胞病毒。

  在5名对更昔洛韦无反应的患者中有4名患者都患有囊性纤维化，对药物产生反应的16位患者中仅有2名患者患有囊性纤维化。囊性纤维化患者机体中缺失可以促进食物和药物消化的胰腺酶类；本文研究显示，那些进行肺部移植的囊性纤维化患者往往需要密切监护来确保其机体中含有足量的更昔洛韦水平。（转化医学网360zhyx.com）

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Subtherapeutic ganciclovir (GCV) levels and GCV-resistant cytomegalovirus in lung transplant recipients
Transplant Infectious Disease DOI: 10.1111/tid.12317
J.P. Gagermeier1,*, J.D. Rusinak1, N.S. Lurain2, C.G. Alex1,3, D.F. Dilling1, C.H. Wigfield4 andR.B. Love5
Background
Cytomegalovirus (CMV) infection results in significant morbidity and mortality in lung transplant recipients. Ganciclovir (GCV) has dramatically reduced complications caused by CMV infections. Unfortunately, GCV resistance is identified in 5–10% of CMV-infected patients. Mismatched CMV status and ongoing replication due to immunosuppression are risk factors for drug resistance. Whether subtherapeutic GCV levels contribute to resistance remains unknown.
Methods
A retrospective review was conducted in all 51 patients who underwent lung transplantation between March 2007 and June 2008 at Loyola University Medical Center. GCV resistance and outcome data of CMV-infected patients were analyzed to identify variables that may contribute to suboptimal response to CMV infection.
Results
During the 16-month period, CMV infection was identified in 21 of 51 lung transplant recipients. Ten of 21 patients (47.6%) had CMV infection with early response to GCV, and 11 patients (52.4%) had CMV infection with suboptimal response to GCV. GCV levels were obtained in the 11 CMV-infected patients with suboptimal response. In 6 patients, GCV levels were therapeutic; all 6 had delayed response to GCV. In 5 patients, GCV levels were subtherapeutic; each had persistent suboptimal response to GCV. Genotyping documented GCV-resistant (GCV-R) CMV in all 5 patients. Cystic fibrosis as the diagnosis requiring lung transplantation was associated with GCV-R CMV infection (P = 0.01).
Conclusion
In our lung transplant recipient cohort, GCV levels were subtherapeutic in all patients with persistent suboptimal response to GCV, each of whom had GCV-R CMV infection. In contrast, GCV levels were therapeutic in CMV-infected patients with delayed GCV response.