Susceptibility of irradiated B6D2F1/J mice to Klebsiella pneumoniae administered intratracheally: a pulmonary infection model in an immunocompromised host.

ABSTRACT

Bacteria such as Klebsiella pneumoniae can invade and colonize an immunocompromised host and complicate clinical recovery. In the study reported here, an experimental model of induced pneumonia was developed in 60Co gamma-photon-irradiated mice for the purpose of evaluating efficacy of therapeutic agents. The model was characterized by use of probit analysis of bacterial dose, and microbiologic, and histopathologic results. Bacterial colony-forming-unit (CFU) values producing 50% mortality within 30 days (LD50/30) and their 95% confidence intervals were 4.0 x 10(4) [1.7 x 10(4) - 8.9 x 10(4)] for 0-Gray (Gy)-irradiated mice, 1.9 x 10(4) [7.0 x 10(3) - 4.8 x 10(4)] for 5-Gy-irradiated mice, and 1.0 x 10(3) [2.8 x 10(2) - 3.3 x 10(3)] for 7-Gy-irradiated mice. Probit regression line fits calculated by use of an iterative, weighted least-squares fit, were used to assess a dose-modifying factor (DMF). The DMFs for mortality, compared with that for the 0-Gy dose, with their 95% confidence intervals, were 2.2 [0.63 - 7.7] for the 5-Gy and 38.9 [9.6 -165.0] for 7-Gy doses. The 5-Gy probit line did not significantly differ (P = 0.21) from the 0-Gy probit line (dose ratios did not significantly differ from 1), whereas the 7-Gy probit line differed significantly from the 0-Gy probit line (P < 0.001). These results demonstrate that 7-Gy 60Co gamma-photon radiation in combination with intratracheal K. pneumoniae challenge induces a valid pulmonary infection model in immunocompromised female B6D2F1/J mice.