Hall C B, Dolin R, Gala C L, Markovitz D M, Zhang Y Q, Madore P H, Disney F A, Talpey W B, Green J L, Francis A B
Pediatrics. 1987 Aug;80(2):275-82.
Treatment with rimantadine of influenza in children and the potential development of resistance in clinical isolates associated with therapy have not been previously studied. We compared rimantadine to acetaminophen therapy in a controlled, double-blind study of 91 children with influenza-like illness. Of 69 children with proven influenza A/H3N2 infection, 37 received rimantadine and 32 received acetaminophen for five days. Children receiving rimantadine showed significantly greater reduction in fever and improvement in daily scores for symptoms and severity of illness during the first three days. Viral shedding also diminished significantly during the first two days but subsequently increased such that by days 6 and 7 the proportion of children shedding virus, as well as the quantity of virus shed, was significantly greater in the rimantadine group. During the seven-day study, of the 22 children in the rimantadine group with serial isolates tested, ten (45.5%) had resistant isolates compared with two (12.5%) of those with serial isolates in the acetaminophen group (P less than .03). Thus, of the total 37 children in the rimantadine group, 27% were found to have resistant isolated compared with 6% in the total group receiving acetaminophen (P less than .04). Furthermore, the mean inhibitory concentration of rimantadine increased with time in the rimantadine group (r = .4, P = .002) but not in the acetaminophen group. Rimantadine therapy, thus, appears to be significantly more effective than acetaminophen in ameliorating the clinical signs and symptoms of influenza in children. Treatment with rimantadine was also associated with increased viral shedding after the medication was discontinued and with the development of resistance in the clinical isolates, the significance of which is unknown.
以前尚未研究过金刚烷胺治疗儿童流感以及与治疗相关的临床分离株中耐药性的潜在发展情况。在一项对91名患有流感样疾病儿童的对照双盲研究中，我们将金刚烷胺与对乙酰氨基酚疗法进行了比较。在69名经证实感染甲型H3N2流感的儿童中，37名接受了金刚烷胺治疗，32名接受了对乙酰氨基酚治疗，为期五天。接受金刚烷胺治疗的儿童在头三天发热明显减轻，症状和疾病严重程度的每日评分有所改善。在前两天病毒排泄也显著减少，但随后增加，以至于在第6天和第7天，金刚烷胺组中排出病毒的儿童比例以及排出的病毒量都显著更高。在为期七天的研究中，金刚烷胺组22名接受连续分离株检测的儿童中有10名（45.5%）有耐药分离株，而对乙酰氨基酚组接受连续分离株检测的儿童中有2名（12.5%）有耐药分离株（P小于0.03）。因此，在金刚烷胺组的37名儿童中，发现27%有耐药分离株，而接受对乙酰氨基酚治疗的总组中这一比例为6%（P小于0.04）。此外，金刚烷胺组中金刚烷胺的平均抑制浓度随时间增加（r = 0.4，P = 0.002），而对乙酰氨基酚组则没有。因此，金刚烷胺疗法在改善儿童流感的临床体征和症状方面似乎明显比对乙酰氨基酚更有效。金刚烷胺治疗还与停药后病毒排泄增加以及临床分离株中耐药性的产生有关，其意义尚不清楚。
