Houck P, Hemphill M, LaCroix S, Hirsh D, Cox N
Health Care Financing Administration, Region X, Seattle, Wash.
Arch Intern Med. 1995 Mar 13;155(5):533-7.
Amantadine hydrochloride and rimantadine hydrochloride have been used for treatment and prevention of influenza A infection in nursing home residents. Outbreaks of influenza A (H3N2) virus infection occurred in three nursing homes in Yakima County, Washington, during January 1992. Amantadine was used for case treatment and prophylaxis in all three nursing homes.
Ten influenza A (H3N2) viruses isolated during the outbreaks were examined for resistance to amantadine and rimantadine by means of an enzyme immunoassay and by sequencing of the viral nucleic acid that encodes the transmembrane domain of the M2 protein.
Five of the outbreak strains were resistant and had the same mutation (position 31, serine to asparagine) in the M2 protein. The resistant viruses included one that had been recovered prior to any use of amantadine and another that was recovered within 48 hours of the first drug administration.
To our knowledge, this is the first report of influenza A virus with RNA sequence-documented resistance to amantadine and rimantadine without exposure to either drug, and the shortest reported period between institution of amantadine therapy and isolation of a resistant influenza A virus strain. These results suggest that surveillance for amantadine- and rimantadine-resistant influenza A is needed, because use of these drugs will probably increase.
盐酸金刚烷胺和盐酸金刚乙胺已被用于疗养院居民甲型流感感染的治疗和预防。1992年1月,华盛顿州亚基马县的三家疗养院发生了甲型(H3N2)病毒感染疫情。在所有三家疗养院中,均使用金刚烷胺进行病例治疗和预防。
通过酶免疫测定法以及对编码M2蛋白跨膜结构域的病毒核酸进行测序,对疫情期间分离出的10株甲型(H3N2)病毒进行了金刚烷胺和金刚乙胺耐药性检测。
5株疫情毒株具有耐药性,且M2蛋白存在相同突变(第31位,丝氨酸突变为天冬酰胺)。耐药病毒包括一株在未使用任何金刚烷胺之前分离出的毒株,以及另一株在首次用药后48小时内分离出的毒株。
据我们所知,这是首次报告未经接触任何一种药物即对金刚烷胺和金刚乙胺具有RNA序列记录耐药性的甲型流感病毒,也是报告中金刚烷胺治疗开始至耐药甲型流感病毒株分离的最短时间。这些结果表明,鉴于这些药物的使用可能会增加,有必要对耐金刚烷胺和耐金刚乙胺的甲型流感进行监测。