Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine.
Amantadine- and rimantadine-resistant viruses have been recovered from approximately 30% of patients treated for acute H3N2 subtype influenza and less often from their close contacts receiving drug prophylaxis. The limited data suggest that resistant viruses can emerge rapidly during drug therapy, as early as 2-3 days into treatment. These viruses retain their resistance phenotype during multiple passages in the laboratory and appear to be genetically stable in this regard. Studies in families and in nursing homes indicate that resistant isolates appear to be transmissible from treated patients and cause typical influenza in contacts receiving drug prophylaxis. It is unknown whether resistant human viruses are capable of competing with wild-type ones during multiple cycles of infection in the absence of the drug. These viruses appear to be pathogenic, and no evidence indicates that they differ from wild-type strains. Thus, these viruses clearly possess the biologic properties that are associated with clinically important drug resistance. However, limited information is available to assess their actual impact. It is unknown what degree of selective drug pressure would be required to cause substantial transmission of resistant viruses during community outbreaks. Natural selection of antigenic variants and disappearance of previous variants may prevent the emergence of viruses that have been altered in the genes coding both for the surface glycoproteins and for the M2 protein. However, the emergence of drug-resistant influenza viruses appears to pose potential clinical problems in certain epidemiologic situations involving close contact with treated patients.
Hayden
F G
FG
Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville.
Hay
A J
AJ
D000547:Amantadine / Q000494:pharmacology; D000818:Animals; D004352:Drug Resistance, Microbial / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity; D007251:Influenza, Human / Q000188:drug therapy / Q000382:microbiology / Q000635:transmission; D012299:Rimantadine / Q000494:pharmacology; D014774:Virulence
D012299:Rimantadine; D000547:Amantadine