Recovery of drug-resistant influenza A virus during therapeutic use of rimantadine

Abstract

The therapeutic activity of rimantadine and its relationship to the shedding of drug-resistant influenza A virus were assessed in two randomized, double-blind, placebo-controlled trials involving patients with laboratory-documented influenza A virus (H3N2 subtype) illness of 2 days' duration or less. In a family-based study, rimantadine treatment for 10 days (24 children and adults) was associated with significant decreases in the number of days to a 50% reduction in symptoms (mean difference, 2.5 days), days of fever (1.6 days), and days of restricted activity (1.5 days) compared with the results obtained with placebo-treated patients (32 children and adults). Drug-resistant virus was recovered from eight (33%) of the rimantadine recipients on day 5. No differences in patient demographics or illness severity at the time of enrollment in the study were apparent between those who shed resistant virus and those who did not. Illness resolution tended to be slower in those who shed resistant virus compared with that in those who did not. In a study of adults treated for 5 days (six treated with rimantadine, six treated with placebo), resistant virus was recovered in three rimantadine recipients by day 3 of treatment. The results indicate that drug-resistant influenza A virus (H3N2) can be recovered from rimantadine-treated children and adults as early as 2 days after starting treatment, but that rimantadine retains a net therapeutic benefit compared with that of placebo.

Incidence of Amantadine‐Resistant Influenza A Viruses in Sentinel Surveillance Sites and Nursing Homes in Niigata, Japan

“…However, only one of them was obtained from a patient who had received amantadine against influenza virus. Up to approximately one-third of the patients shed resistant viruses when amantadine or rimantadine is used for therapy (7,10,12). Transmission of drug-resistant viruses to close, sensitive contacts in families and other semi-closed settings has been described (5,6,9,12,14,(20)(21)(22).…”

Influenza virus neuraminidase: Structure, antibodies, and inhibitors

“…Furthermore, drug-resistant virus can be isolated from humans as early as 2 days from the beginning of treatment with rimantadine (Hayden et al, 1991). Despite the rapid apThe next level of assay is in tissue culture, where the capacpearance of resistance, the drug displays a positive therapeutic ity of the inhibitors to stop multicycle replication of virus can benefit compared to placebo.…”

Recurrence and Persistence of Fever in Children Who Developed Amantadine-Resistant Influenza Viruses after Treatment

“…In an earlier study (Hall et al 1987), illness severity which scored late in therapy tended to be higher in rimantadine-treated children who shed resistant viruses compared to those who did not, but statistical signifi cance was not demonstrated. Furthermore, another study (Hayden et al 1991) indicated that average temperatures did not differ between the rimantadine groups over the fi rst 4 days of treatment, but a non-signifi cant elevation of temperature appeared that shed resistant virus on treatment day 5. Thus, the present study is the fi rst to show signifi cant recurrence and persistence of fever in children who shed resistant infl uenza viruses after treatment.…”

“…In order to determine the clinical signifi cance of drug-resistant virus from treated patients, reduction of fever and improvement of daily scores for symptoms and severity of illness was used in the previous studies (Hall et al 1987;Thompson et al 1987;Hayden et al 1989Hayden et al , 1991. For this paper, only temperature data but not other symptoms was analyzed since it was the only objective measurement that was not affected by biases from doctors' or participants' feelings or judgments.…”

“…However, patients treated with amantadine or rimantadine shed drug-resistant viruses later (Hayden et al 1989(Hayden et al , 1991Suzuki et al 2003), especially after 5-7 days of therapy (Hall et al 1987). Approximately, one-third of the patients develop such resistance (Hayden and Hay 1992;Saito et al 2002).…”