Reddy Anita J, Zaas Aimee K, Hanson Kimberly E, Palmer Scott M
Division of Pulmonary, Allergy and Critical Care Medicine, Duke University Medical Center, Durham, North Carolina, USA.
J Heart Lung Transplant. 2007 Dec;26(12):1286-92. doi: 10.1016/j.healun.2007.09.012. Epub 2007 Nov 19.
Cytomegalovirus (CMV) disease is a major cause of morbidity and mortality after lung transplantation despite ganciclovir prophylaxis. The emergence of ganciclovir-resistant CMV in lung transplant patients has been reported, although the optimal strategy for the management of these infections remains uncertain. A review of the results of glanciclovir susceptibility testing in lung transplant recipients was performed.
We found 54% (113 of 210) of lung transplant patients developed CMV infection over a 4-year study period with ganciclovir-resistant CMV infection occurring in >5% of patients (6 of 113). The demographic and clinical characteristics of patients who developed ganciclovir-resistant vs -sensitive CMV infection were similar, although 50% (3 of 6) patients who developed resistance were CMV mismatched (D(+)/R(-) serology). All patients' CMV isolates had mutations in the UL97 gene. In addition, the 3 mismatch patients also had CMV with mutations in the UL54 gene.
Treatment with a combination of foscarnet and ganciclovir or foscarnet alone for ganciclovir-resistant infection led to a significant reduction in virologic load in all patients (p = 0.03), although transient increases in viremia were observed in some patients early after treatment. Renal function worsened after treatment, but overall it was not significantly different from pre-treatment values (p = 0.07).
Single or combination therapy with foscarnet is effective for treatment of ganciclovir-resistant isolates and excessive concern regarding toxicity should not preclude consideration of these treatments when clinically indicated.
尽管使用更昔洛韦进行预防,巨细胞病毒(CMV)疾病仍是肺移植后发病和死亡的主要原因。已有报道肺移植患者中出现了对更昔洛韦耐药的CMV,尽管这些感染的最佳管理策略仍不确定。我们对肺移植受者更昔洛韦敏感性检测结果进行了综述。
在一项为期4年的研究中,我们发现54%(210例中的113例)的肺移植患者发生了CMV感染,其中超过5%(113例中的6例)的患者发生了对更昔洛韦耐药的CMV感染。发生对更昔洛韦耐药与敏感CMV感染的患者的人口统计学和临床特征相似,不过50%(6例中的3例)发生耐药的患者为CMV血清学不匹配(D(+)/R(-))。所有患者的CMV分离株在UL97基因中均有突变。此外,3例血清学不匹配的患者其CMV的UL54基因也有突变。
对于耐更昔洛韦感染,使用膦甲酸钠和更昔洛韦联合治疗或单独使用膦甲酸钠治疗均使所有患者的病毒载量显著降低(p = 0.03),不过在治疗后的早期,一些患者出现了病毒血症的短暂升高。治疗后肾功能恶化,但总体与治疗前的值无显著差异(p = 0.07)。
膦甲酸钠单药治疗或联合治疗对耐更昔洛韦的分离株有效,在临床有指征时,不应因过度担心毒性而不考虑这些治疗方法。