Understanding the Host Inflammatory Response to Wound Infection: An In Vivo Study of Klebsiella pneumoniae in a Rabbit Ear Wound Model

Wound infection development is critically dependent on the complex interactions between bacteria and host. Klebsiella pneumoniae has become an increasingly common wound pathogen, but its natural history within wounds has never been studied. Using a validated, in vivo rabbit ear model, wounds were inoculated with K. pneumoniae at different concentrations 10exp2-10exp7 colony-forming units with measurement of viable and nonviable bacterial counts, histological wound-healing parameters, and host inflammatory gene expression at multiple time points postin-oculation 48, 96, and 240 hours. Bacteria and wound morphologies were evaluated with scanning electron microscopy. Comparable experiments were performed in ischemic ears to model immune response impairment. All wounds, despite different inoculants, equilibrated to similar bacterial concentrations by 96 hours. With a 10exp 6 colony-forming units inoculant, wounds at 240 hours showed decreased bacterial counts p less than 0.01, with a corresponding improvement in healing p less than 0.01 and a decrease in inflammatory response p less than 0.05. In contrast, ischemic wounds revealed impaired inflammatory gene expression p less than 0.05 resulting in higher steady-state bacterial concentrations p less than 0.01, impaired healing p less than 0.05, and biofilm formation on scanning electron microscopy. We conclude that a normal inflammatory response can effectively stabilize and overcome a K. pneumoniae wound infection. An impaired host cannot control this bacterial burden, preventing adequate healing while allowing bacteria to establish a chronic presence. Our novel study quantitatively validates the host immune response as integral to wound infection dynamics.