Intravenous peramivir inhibits viral replication, and leads to bacterial clearance and prevention of mortality during murine bacterial co-infection caused by influenza A(H1N1)pdm09 virus and Streptococcus pneumoniae.
BACKGROUND
Influenza virus infection increases susceptibility to bacterial infection and mortality in humans. Although the efficacy of approved intravenous peramivir, a neuraminidase (NA) inhibitor, against influenza virus infection has been reported, its efficacy against bacterial co-infection, which occurs during the period of viral shedding, was not fully investigated. To further understand the significance of treatment with peramivir, we assessed the efficacy of peramivir against a bacterial co-infection model in mice caused by clinically isolated influenza A(H1N1)pdm09 virus and Streptococcus pneumoniae.


METHODS
Mice were infected with influenza A(H1N1)pdm09. Peramivir was intravenously administered after the viral infection. At 2days post viral infection, the mice were infected with S. pneumoniae. Peramivir efficacy was measured by the survival rates and viral titers, bacterial titers, or proinflammatory cytokine concentrations in lung homogenates.


RESULTS
Peramivir treatment reduced the mortality of mice infected with influenza virus and S. pneumoniae. The survival rate in the peramivir-treated group was significantly higher than that in the oseltamivir-treated group. Viral titers and proinflammatory cytokine responses in the peramivir-treated group were significantly lower than those in the oseltamivir-treated group until at 2days post viral infection. Bacterial titer was significantly lower in the peramivir-treated group than in the oseltamivir-treated group at 4days post viral infection.


CONCLUSIONS
These results demonstrated that peramivir inhibits viral replication, consequently leading to bacterial clearance and prevention of mortality during severe murine bacterial co-infection, which occurs during the period of viral shedding, with the efficacy of peramivir being superior to that of oseltamivir.
Infectious Diseases, Discovery Research Laboratory for Core Therapeutic Area, Shionogi & Co., Ltd., Osaka, Japan. Electronic address: motoyasu.oonishi@shionogi.co.jp.
Motoyasu
M
Onishi
Infectious Diseases, Discovery Research Laboratory for Core Therapeutic Area, Shionogi & Co., Ltd., Osaka, Japan.
Mitsutaka
M
Kitano
Infectious Diseases, Discovery Research Laboratory for Core Therapeutic Area, Shionogi & Co., Ltd., Osaka, Japan.
Keiichi
K
Taniguchi
Infectious Diseases, Discovery Research Laboratory for Core Therapeutic Area, Shionogi & Co., Ltd., Osaka, Japan.
Tomoyuki
T
Homma
Infectious Diseases, Discovery Research Laboratory for Core Therapeutic Area, Shionogi & Co., Ltd., Osaka, Japan.
Masanori
M
Kobayashi
Infectious Diseases, Discovery Research Laboratory for Core Therapeutic Area, Shionogi & Co., Ltd., Osaka, Japan.
Tomokazu
T
Yoshinaga
Infectious Diseases, Discovery Research Laboratory for Core Therapeutic Area, Shionogi & Co., Ltd., Osaka, Japan.
Akira
A
Naito
Infectious Diseases, Discovery Research Laboratory for Core Therapeutic Area, Shionogi & Co., Ltd., Osaka, Japan.
Akihiko
A
Sato
D000146:Acids, Carbocyclic; D061605:Administration, Intravenous; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D058491:Bacterial Load / Q000187:drug effects; D060085:Coinfection / Q000188:drug therapy* / Q000401:mortality; D003517:Cyclopentanes / Q000008:administration & dosage*; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004285:Dogs; D006146:Guanidines / Q000008:administration & dosage*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000188:drug therapy* / Q000401:mortality; D053139:Oseltamivir / Q000008:administration & dosage; D011008:Pneumococcal Infections / Q000150:complications* / Q000401:mortality; D013296:Streptococcus pneumoniae / Q000187:drug effects*; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D003517:Cyclopentanes; D016207:Cytokines; D006146:Guanidines; D053139:Oseltamivir; C414210:peramivir
Bacterial co-infection; Influenza virus; Neuraminidase inhibitor; Peramivir; Streptococcus pneumoniae