Animal models of chronic bacterial airway
infections are limited in relevance to human
infection, not only because of limitations present in all animal models (e.g., abnormal sequence of pathologic events, artificial imposition of
infection involving large inocula, dissimilar host pharmacokinetic attributes), but especially because underlying
disease (chronic obstructive pulmonary disease, or
COPD) is usually absent. A major problem in establishing chronic lung
infection models is the rapid clearance of bacteria instilled into the drugs; this can be overcome by encasing bacteria into
agar beads to restrict phagocytosis. Despite these limitations, animal models based upon
agar bead-encased inocula have provided
persistent infections resulting in lung pathology and high humoral immune responses similar to that observed in patients with
COPD. Such models have illuminated some aspects of the virulence of the bacteria, the involvement of bacterial exoenzymes in promoting lung damage, the potential of vaccination to restrict infectious exacerbations, and the activity of subminimal inhibitory concentrations of
antibiotics in reducing lung damage by inhibiting exoenzyme release. Animal models have also shown that anti-inflammatory
therapy may be effective in reducing
inflammation-associated lung damage. Despite the limitations of chronic lung
infection models, they may provide insight into pathologic events and positive therapeutic intervention for lung
infections of patients with
COPD.