3.1 Pneumococcal superinfection The infectious agent most often complicating influenza is Streptococcus pneumoniae. In a superinfection model, pneumococcal pneumonia after influenza virus infection was established in six-week old mice using sublethal doses of both microbes (Hayashi et al., 2006). S. pneumoniae was inoculated intranasally 7 days after exposure to influenza virus and death in the presence of both agents only began at day 4 post bacterial exposure. The efficacy of several quinolones against bacteria-induced pneumonia in this model was evaluated, with gatifloxacin used successfully to treat the pneumococcal infection. In another model of secondary pneumococcal pneumonia during influenza A virus infection, the pathology and immunology that led to fatal disease was studied by specifically looking at cytokine profiles (Smith et al., 2007). Influenza-infected mice challenged with each of 3 serotypes of S. pneumoniae developed a severe, necrotic pneumonia, characterized by markedly elevated levels of both pro- and anti-inflammatory molecules in the lungs, accompanied by a massive influx of neutrophils. Death was associated with the development of pneumonia and lung inflammation, but not with bacteremia. Thus, this model may be used to delineate factors associated with the pathogenesis of severe mixed lung infections.