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更昔洛韦与膦甲酸钠联合治疗获得性免疫缺陷综合征患者临床耐药性巨细胞病毒性视网膜炎

Combination ganciclovir and foscarnet in the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

作者信息

Kuppermann B D, Flores-Aguilar M, Quiceno J I, Rickman L S, Freeman W R

机构信息

Department of Ophthalmology, University of California, San Diego.

出版信息

Arch Ophthalmol. 1993 Oct;111(10):1359-66. doi: 10.1001/archopht.1993.01090100067029.

Abstract

OBJECTIVE

To assess the clinical response and patient tolerance to daily infusions of both ganciclovir sodium and foscarnet sodium for the treatment of clinically resistant cytomegalovirus retinitis in patients with acquired immunodeficiency syndrome.

DESIGN AND PATIENTS

Nine patients with clinically resistant cytomegalovirus retinitis who had shown progression of retinitis despite extended intravenous induction single-drug therapy or alternating therapy with induction doses of ganciclovir or foscarnet at 6 weeks were subsequently treated with a combination of ganciclovir and foscarnet. The dosing regimen for induction combination therapy was ganciclovir at 5 mg/kg every 12 hours and foscarnet at 60 mg/kg every 8 hours. Maintenance combination therapy was ganciclovir at 5 mg/kg every 12 to 24 hours and foscarnet at 90 to 120 mg/kg every day. Patients were observed closely for signs of a toxic effect or intolerance to the drug regimen.

RESULTS

All patients exhibited a favorable response to combination therapy, with complete healing of retinitis in 12 of 14 eyes and partial healing of retinitis with decreased border activity and a cessation of border advancement in two of 14 eyes. Two of the nine patients stopped receiving combination therapy before completion of the study owing to their dissatisfaction with the time commitment. The regimen was otherwise well tolerated, with no significant medical toxic effects attributable to the drugs requiring cessation of therapy.

CONCLUSIONS

Combination anticytomegalovirus therapy should be considered in those patients who have shown a poor clinical response to sustained single-drug induction therapy and alternating drug therapy. As survival time for patients with cytomegalovirus retinitis continues to improve, clinical resistance may become more common. Further work to delineate the optimal dosing and indications for combination therapy will be important.

摘要

目的

评估每日输注更昔洛韦钠和膦甲酸钠治疗获得性免疫缺陷综合征患者临床耐药性巨细胞病毒性视网膜炎的临床反应和患者耐受性。

设计与患者

9例临床耐药性巨细胞病毒性视网膜炎患者,尽管接受了延长的静脉诱导单药治疗或6周时使用诱导剂量的更昔洛韦或膦甲酸钠交替治疗,视网膜炎仍有进展,随后接受更昔洛韦和膦甲酸钠联合治疗。诱导联合治疗的给药方案为更昔洛韦5mg/kg,每12小时1次,膦甲酸钠60mg/kg,每8小时1次。维持联合治疗为更昔洛韦5mg/kg,每12至24小时1次,膦甲酸钠90至120mg/kg,每天1次。密切观察患者是否有药物治疗的毒性作用或不耐受迹象。

结果

所有患者对联合治疗均表现出良好反应,14只眼中12只视网膜炎完全愈合,14只眼中2只视网膜炎部分愈合,边界活动度降低且边界进展停止。9例患者中有2例因对时间投入不满意在研究完成前停止接受联合治疗。该方案耐受性良好,没有因药物导致需要停止治疗的明显医学毒性作用。

结论

对于持续单药诱导治疗和交替药物治疗临床反应不佳的患者,应考虑联合抗巨细胞病毒治疗。随着巨细胞病毒性视网膜炎患者生存时间的持续改善,临床耐药可能会变得更加常见。进一步明确联合治疗的最佳给药剂量和适应证的工作将很重要。

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