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肾移植患者疱疹感染的预防,特别关注巨细胞病毒。

Prophylaxis against herpes infections in kidney transplant patients with special emphasis on CMV.

作者信息

Birkeland S A, Andersen H K, Gahrn-Hansen B

机构信息

Department of Nephrology, Odense University Hospital, Denmark.

出版信息

Scand J Infect Dis. 1998;30(3):221-6. doi: 10.1080/00365549850160837.

Abstract

METHOD

Since 1990, we have treated all kidney transplanted patients with cyclosporin (CsA)+ an initial 10 d antilymphocyte globulin (ALG) course, from September 1995 supplemented with mycophenolate mofetil (MMF). In 170 consecutive transplantations from June 1992 to the end of 1996, aciclovir 3200 mg/d (adjusted for kidney function and in children to age) was given prophylactically for 3 months post-transplantation (Tx), monitored with systematic and frequent tests for HSV and CMV. In case of CMV infection, we gave ganciclovir intravenously (oral ganciclovir from 1996) in doses according to kidney function for 3 months, followed by a further 3 months observation and monitoring period. In case of acute cellular rejection, ganciclovir was given during the 10-d OKT3 course and 1 week further. In case of delayed graft function combined with aciclovir side effects, ganciclovir was given until aciclovir could be reintroduced.

RESULTS

39% were HSV seronegative at Tx. There were no seroconversions or reactivations within the observation period. No mucocutaneous HSV infections was observed. No resistant strains developed. 26% were both HSV and CMV negative at Tx. 52% were CMV negative at Tx. 30% experienced a CMV infection post-transplant. The patients were grouped according to CMV status in the donor (D) and recipient (R) before Tx. We found approximately the same number of patients in the 4 CMV groups D-/R-, D+/R-, D-/R+ and D+/R+. Most infections occurred in the D+/R- group compared to D-/R- (p = 0.009). A significant increase in the number of CMV infections occurred in this subgroup when we gave reduced doses in case of delayed graft function (p = 0.015), from 1994. We observed only 1 CMV disease (in 1992). Serological EBV testing were performed concomitantly. No correlation was seen between CMV and EBV infections. From September 1995 we have treated all transplanted patients (n = 40) with CsA/ALG/MMF. We found no significant increase in CMV infections in this group.

CONCLUSIONS

Prophylaxis with aciclovir (combined with ganciclovir during acute rejections and in case of delayed graft function with aciclovir side effects) gives a good protection against HSV and CMV infections and prevents CMV disease effectively. High-dose aciclovir post-transplantation (or shift to ganciclovir) seems to be important to obtain effective prophylaxis. Better immunosuppression with MMF does not result in more CMV infections.

摘要

方法

自1990年起,我们对所有肾移植患者采用环孢素(CsA)加初始10天抗淋巴细胞球蛋白(ALG)疗程进行治疗,从1995年9月起加用霉酚酸酯(MMF)。在1992年6月至1996年底连续进行的170例移植手术中,移植后(Tx)预防性给予阿昔洛韦3200mg/d(根据肾功能及儿童年龄调整剂量),持续3个月,并通过系统且频繁的检测监测单纯疱疹病毒(HSV)和巨细胞病毒(CMV)。若发生CMV感染,根据肾功能给予静脉用更昔洛韦(1996年起为口服更昔洛韦),持续3个月,随后再进行3个月的观察和监测期。若发生急性细胞排斥反应,在10天的OKT3疗程及之后1周给予更昔洛韦。若出现移植肾功能延迟恢复并伴有阿昔洛韦副作用,则持续给予更昔洛韦直至可重新使用阿昔洛韦。

结果

移植时39%的患者HSV血清学阴性。观察期内未出现血清转化或再激活情况。未观察到皮肤黏膜HSV感染。未出现耐药菌株。移植时26%的患者HSV和CMV均为阴性。移植时52%的患者CMV阴性。30%的患者移植后发生CMV感染。根据移植前供体(D)和受体(R)的CMV状态对患者进行分组。我们发现4个CMV组D - /R - 、D + /R - 、D - /R + 和D + /R + 中的患者数量大致相同。与D - /R - 组相比,大多数感染发生在D + /R - 组(p = 0.009)。从1994年起,当出现移植肾功能延迟恢复时给予较低剂量药物,该亚组中CMV感染数量显著增加(p = 0.015)。我们仅观察到1例CMV疾病(在1992年)。同时进行了EB病毒(EBV)血清学检测。未发现CMV和EBV感染之间存在相关性。自1995年9月起,我们对所有移植患者(n = 40)采用CsA/ALG/MMF治疗。我们发现该组中CMV感染无显著增加。

结论

阿昔洛韦预防(在急性排斥反应期间及出现移植肾功能延迟恢复并伴有阿昔洛韦副作用时联合更昔洛韦)可有效预防HSV和CMV感染,并有效预防CMV疾病。移植后高剂量阿昔洛韦(或改用更昔洛韦)对于获得有效的预防似乎很重要。使用MMF进行更好的免疫抑制不会导致更多的CMV感染。

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