Correlation between the in vitro and in vivo Effects of Fourteen Beta-Lactam Compounds in Mice with Systemic Infection.

Tsuji, Akiyoshi; Kaneko, Yasuko; Yamaguchi, Keizo; Goto, Sachiko

The in vivo effect of 14 β-lactam compounds was compared with the in vitro effect in mice systemically infected with Pseudomonas aeruginosa E7 or Klebsiella pneumoniae 3K-25. The microorganisms were inoculated intraperitoneally, and the in vivo effect of the drug was expressed as the median effective dose (ED50) determined by subcutaneous administration of the drug 1 h after the inoculation. In the mice infected with P. aeruginosa, the ability of the drug to kill the bacteria in a short time (killing activity) was markedly correlated with the ED50 (r = -0.704), but there was no correlation with the maximum concentration, half-life or area under the curve of the drug. The coefficient of multiple correlation of the ED50 with killing activity + time above the minimum bactericidal concentration (MBC) was 0.824 (contribution rate, 67.9%). In the mice infected with K pneumoniae, the killing activity was highly correlated with MBC (r = 0.899), and the coefficient of multiple correlations with MBC + time above MBC was 0.919 (contribution rate, 84.4%). These results suggest that β-lactam compounds have strong bactericidal activity in mice with systemic infection and that drugs with a long time above MBC are effective for this condition. Copyright © 1994 S. Karger AG, Basel

Chemotherapy (0009-3157), 1994, Vol 40, Issue 5, p324

0009-3157

Academic Journal

10.1159/000239214