title: The effect of intravenous peramivir, compared with oral oseltamivir, on the outcome of post-influenza pneumococcal pneumonia in mice.
abstract: BACKGROUND
  Pneumococcal pneumonia often occurs secondary to influenza infection and accounts for a large proportion of the morbidity and mortality associated with seasonal and pandemic influenza outbreaks. Peramivir is a novel, intravenous neuraminidase inhibitor that exhibits potent antiviral activity against influenza A and B viruses. We investigated the efficacy of peramivir for modulating the severity of secondary pneumococcal pneumonia.
  
  
  METHODS
  CBA/JNCrlj mice, infected with influenza virus and superinfected with Streptococcus pneumoniae, were treated with either intravenous peramivir (single or multiple doses of 60 mg/kg/day) or oral oseltamivir at doses of 10 or 40 mg/kg/day in divided doses. The survival rate, viable bacterial count and virus titre in the lungs, as well as cytokine/chemokine concentration and histopathological findings were compared between both groups.
  
  
  RESULTS
  The median duration of survival of coinfected mice was significantly prolonged by treatment with multiple doses of peramivir, relative to mice treated with oseltamivir at either dose. Viable bacterial counts and virus titres in the lungs were significantly reduced by intravenous peramivir treatment compared with no treatment or oral oseltamivir treatment. The production of inflammatory cytokines/chemokines was also significantly suppressed by multiple dosing of peramivir compared with oseltamivir. Increased survival appeared to be mediated by decreased inflammation, manifested as lower levels of inflammatory cells and proinflammatory cytokines in the lungs and less severe histopathological findings. The lungs of mice treated with multiple doses of peramivir showed mild inflammatory changes compared to oseltamivir.
  
  
  CONCLUSIONS
  This study demonstrated that a multiple-dose regimen of intravenous peramivir was more efficacious than a single peramivir dose or multiple doses of oseltamivir for improving outcomes in pneumococcal pneumonia following influenza virus infection in mice.
authors: Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Akitaka
authors: A
authors: Tanaka
authors: Shigeki
authors: S
authors: Nakamura
authors: Masafumi
authors: M
authors: Seki
authors: Naoki
authors: N
authors: Iwanaga
authors: Toshiki
authors: T
authors: Kajihara
authors: Mitsutaka
authors: M
authors: Kitano
authors: Tomoyuki
authors: T
authors: Homma
authors: Shintaro
authors: S
authors: Kurihara
authors: Yoshifumi
authors: Y
authors: Imamura
authors: Taiga
authors: T
authors: Miyazaki
authors: Koichi
authors: K
authors: Izumikawa
authors: Hiroshi
authors: H
authors: Kakeya
authors: Katsunori
authors: K
authors: Yanagihara
authors: Shigeru
authors: S
authors: Kohno
mesh_terms: D000146:Acids, Carbocyclic; D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D054426:Chemokine CXCL2 / Q000096:biosynthesis / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology; D060085:Coinfection; D003517:Cyclopentanes / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000821:virology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D053139:Oseltamivir / Q000494:pharmacology*; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000382:microbiology / Q000401:mortality*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000276:immunology; D016019:Survival Analysis; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000146:Acids, Carbocyclic; D000998:Antiviral Agents; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D003517:Cyclopentanes; D006146:Guanidines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C074302:keratinocyte-derived chemokines; D053139:Oseltamivir; D007371:Interferon-gamma; C414210:peramivir