LIPOSOMAL CEFOXITIN IN A PORCINE MODEL OF INTRAABDOMINAL SEPSIS - BACTERICIDAL EFFICACY

The bactericidal effect of free versus liposomal cefoxitin was evaluat ed in the major reticuloendothelial organs in a porcine model of intra -abdominal sepsis. Yorkshire Landrace pigs were inoculated with 3.2 X 10(10) (n = 5) or 1.4 x 10(11) (n = 7) cfu of Escherichia coli mixed i n sterile feces/animal. Two treatment groups inoculated with 1.4 x 10( 11) cfu were established: free cefoxitin (n = 9) and liposomal cefoxit in (n = 9). All animals were maintained under anesthesia and euthanize d after 24 h. The number of E. coli recovered in the liver, lungs, and spleen was significantly affected by inoculum size (p <.05). The live r had significantly higher numbers of bacteria (p <.05) compared with the other organs, regardless of the inoculum size. The liver and the l ung of the liposomal cefoxitin-treated group showed significantly lowe r numbers of E. coli (5.0 x 10(4) and 6.3 x 10(2), respectively) compa red with the untreated (liver, 6.3 x 10(7); lung, 2.0 x 10(6)) and fre e cefoxitin (liver, 5.0 x 10(6); lung, 7.9 x 10(4))-treated groups (p <.05). At 2 h following the injection of free and liposomal cefoxitin, the decrease of E. coli in peritoneal fluid compared with the nontrea ted septic group was significant (p <.05). No growth was observed from blood cultures taken 24 h after sepsis induction. All control experim ents yielded negative cultures. The results of these experiments demon strated that liposomal cefoxitin exerts an enhanced bactericidal effec t in liver and lungs during Gram-negative sepsis.