Published ahead of print on July 13, 2005, doi:10.1165/rcmb.2005-0053OC
© 2005 American Thoracic Society DOI: 10.1165/rcmb.2005-0053OC Dynamics of Intrapulmonary Bacterial Growth in a Murine Model of Repeated MicroaspirationDepartments of Emergency Medicine and Mathematics, University of Michigan, Ann Arbor, Michigan Correspondence and requests for reprints should be addressed to John G. Younger, Department of Emergency Medicine, 7679 Kresge Research Building I, 200 Zina Pitcher Place, Ann Arbor, MI 48109. E-mail: jyounger{at}umich.edu To study the change in intrapulmonary bacterial growth rate over time during Gram-negative pneumonia, a two-hit model of recurrent bacterial aspiration was developed in mice. A mutant of Klebsiella pneumoniae was isolated that could be distinguished from the wild type when cultured on appropriate media. These strains were intranasally administered, 4 h apart, to mice whose lungs were quantitatively cultured 24 h later. The relative burden of each aspirated inoculum was determined, and, using the administered dose and the number of bacteria from each inoculum present at the end of the experiment, first-order growth constants for each inoculum were calculated. Results indicate that after an initial aspiration of this organism, subsequently aspirated bacteria proliferate more slowly. When two aspirations occurred 4 h apart, the bacteria aspirated first represented 96% of total lung burden at 24 h. The growth constant of the second inoculum was related to the magnitude of the first inoculum in an inverse, nonlinear fashion. When parallel experiments were performed in complement C3-deficient mice, no suppression of the second inoculum was noted, suggesting that early upregulation of antibacterial activity in the lung is a C3-mediated event.
Key Words: pneumonia • mathematical models • complement • Klebsiella pneumoniae This article has been cited by other articles:
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