ABSTRACT
Studies with animal models have demonstrated that viral respiratory tract infections suppress bacterial clearance processes in the lung and that this alteration in host defenses appears to explain the excessive mortality from bacterial pneumonia during influenza epidemics. However, since the pathogenesis of postinfluenza pneumonia and other pneumonias probably involves the aspiration of normal nasopharyngeal flora, injury to major airways associated with influenza infections could also contribute to the development of bacterial pneumonia by increasing bacterial deposition in the peripheral lung. We investigated this possibility by evaluating tracheal clearance processes and spontaneous changes in the tracheal flora in a murine model for acute influenza. During fine-particle aerosol exposures to Staphylococcus aureus, influenza-infected mice retained the same number of bacteria on their proximal tracheal surfaces as did control mice, and the relative adherence of the staphylococci to the trachea was similar in both groups of mice. However, the clearance of viable staphylococci from the trachea was significantly delayed in influenza-infected mice. Control and influenza-infected mice were also evaluated for changes in their normal tracheal flora. Mice with established influenza infections had more frequent spontaneous colonization with gram-negative bacteria, more bacterial isolates per animal, and higher bacterial concentrations in tracheal homogenates than control mice. These changes in tracheal flora were most pronounced on day 7 after virus inoculation and persisted after virus titers were undetectable, but eventually resolved by day 14 after virus infection. Tetracycline therapy started 2 days after virus inoculation prevented the increased colonization. This impaired clearance function and increased spontaneous colonization were associated with morphological evidence of mucosal regeneration. We conclude that spontaneous changes in tracheal flora occur during influenza infections, that these changes reflect, in part, impaired clearance functions, and that such changes could contribute to the development of pneumonia regardless of the clearance capacity of the lung parenchyma.
