Amantadine-resistant influenza A in nursing homes. Identification of a resistant virus prior to drug use.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Houck
P
P
Health Care Financing Administration, Region X, Seattle, Wash.
Hemphill
M
M
LaCroix
S
S
Hirsh
D
D
Cox
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000547:Amantadine / Q000627:therapeutic use*; D001483:Base Sequence; D004196:Disease Outbreaks; D004352:Drug Resistance, Microbial; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009735:Nursing Homes; D012299:Rimantadine / Q000627:therapeutic use*; D017211:Treatment Failure; D014861:Washington / Q000453:epidemiology
D012299:Rimantadine; D000547:Amantadine