tetano
Editor, Senior Moderator
J Infect Dis. 2017 Nov 25. doi: 10.1093/infdis/jix606. [Epub ahead of print]
[h=1]Combination Therapy with Neuraminidase and Polymerase Inhibitors in Nude Mice Infected with Influenza Virus.[/h] Kiso M[SUP]1[/SUP], Lopes TJS[SUP]1,[/SUP][SUP]2[/SUP], Yamayoshi S[SUP]1[/SUP], Ito M[SUP]1[/SUP], Yamashita M[SUP]1[/SUP], Nakajima N[SUP]3[/SUP], Hasegawa H[SUP]3[/SUP], Neumann G[SUP]2[/SUP], Kawaoka Y[SUP]1,[/SUP][SUP]2,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Treatment of immunocompromised, influenza virus-infected patients with the viral neuraminidase inhibitor oseltamivir often leads to the emergence of drug-resistant variants. Combination therapy with compounds that target different steps in the viral life cycle may improve treatment outcomes and reduce the emergence of drug-resistant variants. Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or combinations thereof. Combination therapy for 28-days increased survival times compared with monotherapy, but the animals died after treatment was terminated. Mono- and combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor-resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors. Collectively, our data demonstrate that combination therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor-resistant variants.
[h=4]KEYWORDS:[/h] Influenza; combination therapy; drug resistance; neuraminidase inhibitor; polymerase inhibitor
PMID: 29186472 DOI: 10.1093/infdis/jix606
[h=1]Combination Therapy with Neuraminidase and Polymerase Inhibitors in Nude Mice Infected with Influenza Virus.[/h] Kiso M[SUP]1[/SUP], Lopes TJS[SUP]1,[/SUP][SUP]2[/SUP], Yamayoshi S[SUP]1[/SUP], Ito M[SUP]1[/SUP], Yamashita M[SUP]1[/SUP], Nakajima N[SUP]3[/SUP], Hasegawa H[SUP]3[/SUP], Neumann G[SUP]2[/SUP], Kawaoka Y[SUP]1,[/SUP][SUP]2,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Treatment of immunocompromised, influenza virus-infected patients with the viral neuraminidase inhibitor oseltamivir often leads to the emergence of drug-resistant variants. Combination therapy with compounds that target different steps in the viral life cycle may improve treatment outcomes and reduce the emergence of drug-resistant variants. Here, we infected immunocompromised nude mice with an influenza A virus and treated them with neuraminidase (oseltamivir, laninamivir) or viral polymerase (favipiravir) inhibitors, or combinations thereof. Combination therapy for 28-days increased survival times compared with monotherapy, but the animals died after treatment was terminated. Mono- and combination therapies did not consistently reduce lung virus titers. Prolonged viral replication led to the emergence of neuraminidase inhibitor-resistant variants, although viruses remained sensitive to favipiravir. Overall, favipiravir provided greater benefit than neuraminidase inhibitors. Collectively, our data demonstrate that combination therapy in immunocompromised hosts increases survival times, but does not suppress the emergence of neuraminidase inhibitor-resistant variants.
[h=4]KEYWORDS:[/h] Influenza; combination therapy; drug resistance; neuraminidase inhibitor; polymerase inhibitor
PMID: 29186472 DOI: 10.1093/infdis/jix606