BACKGROUND Cytomegalovirus (CMV) infection causes significant morbidity and mortality in transplant recipients. Ganciclovir and valganciclovir have proven efficacy but are limited by resistance and toxicity, whereas foscarnet typically retains activity when CMV has become resistant to other antivirals. Foscarnet dosing used in practice may be discordant with what is recommended in product labeling, as the result of an unconventional dosing nomogram or prescriber preference; however, it is unknown how discordant foscarnet dosing affects outcomes. OBJECTIVE Our purpose was to characterize the relationship between initial foscarnet dosing intensity (relative to product labeling) and key effectiveness and safety endpoints. STUDY DESIGN This single-center, retrospective study included immunosuppressed adults with CMV viremia who received foscarnet between January 2012-July 2017. Subjects were divided into low dose (LD) and non-low dose (NLD) groups, according to foscarnet dose intensity. The primary endpoint was time-to-CMV eradication. Secondary endpoints included time-to-CMV clearance, acute kidney injury, hematologic toxicity, and mortality. RESULTS Of 87 subjects, 38 met inclusion. Primary immunosuppression reasons were solid organ (63%) or hematopoietic cell transplant (29%). Seventeen and 21 subjects were in the LD and NLD groups, respectively. Median time-to-CMV eradication was 17 days (LD group) versus 13 days (NLD group), p = 0.823. Median time-to-CMV clearance was also non-significant (p = 0.505). There was no association between initial foscarnet dosing intensity and acute kidney injury, hematologic toxicity, or mortality (24% in both groups). CONCLUSIONS These findings suggest outcomes may be sensitive to other factors and underscore the need for further studies to improve understanding of foscarnet dosing in immunosuppressed patients.

中文翻译：

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推荐的膦甲酸酯剂量与巨细胞病毒挽救疗法的改善结局无关。

背景技术巨细胞病毒（CMV）感染在移植受体中引起明显的发病率和死亡率。更昔洛韦和缬更昔洛韦已被证明具有疗效，但受到耐药性和毒性的限制，而当CMV对其他抗病毒药产生耐药性时，膦甲酸通常保持活性。由于非常规的剂量诺模图或处方者的偏爱，实践中使用的膦甲酸酯剂量可能与产品标签中推荐的剂量不一致。然而，未知的膦甲酸酯剂量如何影响疗效。目的我们的目的是表征初始膦甲酸酯剂量（相对于产品标签）与关键有效性和安全性终点之间的关系。研究设计这种单中心的 回顾性研究包括在2012年1月至2017年7月之间接受了膦甲酸保护的免疫抑制的CMV病毒成年成年人。根据膦甲酸的剂量强度，将受试者分为低剂量（LD）组和非低剂量（NLD）组。主要终点是消除CMV的时间。次要终点包括清除CMV的时间，急性肾损伤，血液学毒性和死亡率。结果在87名受试者中，有38名被纳入研究。主要的免疫抑制原因是实体器官（63％）或造血细胞移植（29％）。LD和NLD组分别有17名和21名受试者。根除CMV所需的时间中位数为17天（LD组），而13天（NLD组），p = 0.823。到CMV清除的时间中位数也不显着（p = 0.505）。初始膦甲酸酯剂量与急性肾损伤之间没有关联，血液毒性或死亡率（两组均为24％）。结论这些发现提示预后可能对其他因素敏感，并强调需要进一步研究以提高对免疫抑制患者对膦甲酸酯剂量的了解。