Vora Surabhi B, Brothers Adam W, Waghmare Alpana, Englund Janet A
Division of Infectious Diseases, Department of Pediatrics, University of Washington, Seattle, WA, USA.
Seattle Children's Hospital, Seattle, WA, USA.
Antivir Ther. 2018;23(6):505-511. doi: 10.3851/IMP3238.
Cytomegalovirus (CMV) infection is a major risk factor for mortality in infants with severe combined immunodeficiency (SCID) and other profound immune defects. Specific antiviral therapy must be initiated early and aggressively because of the potential for antiviral resistance, rapid dissemination and poor transplant outcomes. Combination antiviral therapy is routinely administered for some viral infections, but the value of this approach for the treatment of CMV is unclear. Here we explore a strategy of initial combination therapy for high-risk infants with CMV infection.
We reviewed medical records of infants ≤6 months of age hospitalized between 2007-2015 who received ganciclovir (GCV) or foscarnet (FOS) monotherapy or initial combination GCV + FOS for CMV disease. The combination therapy group consisted of severely immunocompromised infants being considered for haematopoietic cell transplantation (HCT).
Four patients received initial combination antiviral therapy and 26 patients received initial monotherapy during the study period. Combination antiviral recipients demonstrated initial improvement in viraemia and two of three who continued with this therapy survived the infection. Clinically significant resistance mutations did not emerge. Toxicity was common; neutropenia, thrombocytopenia and electrolyte abnormalities were the most frequent adverse events in both groups. Creatinine elevation was uncommon in both groups.
Combination GCV + FOS therapy may be a safe alternative to monotherapy in high-risk infants, especially those who are pre-transplant with primary immune deficiency syndromes and high viral loads.
巨细胞病毒(CMV)感染是严重联合免疫缺陷(SCID)及其他严重免疫缺陷婴儿死亡的主要危险因素。由于存在抗病毒耐药、病毒快速播散及移植预后不佳的可能性,必须尽早积极启动特异性抗病毒治疗。对于某些病毒感染常规采用联合抗病毒治疗,但这种方法治疗CMV的价值尚不清楚。在此,我们探讨针对高危CMV感染婴儿的初始联合治疗策略。
我们回顾了2007年至2015年间住院的≤6月龄婴儿的病历,这些婴儿接受了更昔洛韦(GCV)或膦甲酸钠(FOS)单药治疗或GCV + FOS初始联合治疗以治疗CMV疾病。联合治疗组包括考虑进行造血细胞移植(HCT)的严重免疫功能低下婴儿。
在研究期间,4例患者接受了初始联合抗病毒治疗,26例患者接受了初始单药治疗。联合抗病毒治疗的患者病毒血症最初有所改善,继续接受该治疗的3例患者中有2例在感染中存活。未出现具有临床意义的耐药突变。毒性反应常见;两组中最常见的不良事件是中性粒细胞减少、血小板减少和电解质异常。两组中肌酐升高均不常见。
对于高危婴儿,尤其是那些患有原发性免疫缺陷综合征且病毒载量高的移植前婴儿,GCV + FOS联合治疗可能是单药治疗的安全替代方案。