Liposomal cefoxitin in a porcine model of intra-abdominal sepsis: bactericidal efficacy.
The bactericidal effect of free versus liposomal cefoxitin was evaluated 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 in sterile feces/animal. Two treatment groups inoculated with 1.4 x 10(11) cfu were established: free cefoxitin (n = 9) and liposomal cefoxitin (n = 9). All animals were maintained under anesthesia and euthanized after 24 h. The number of E. coli recovered in the liver, lungs, and spleen was significantly affected by inoculum size (p < .05). The liver had significantly higher numbers of bacteria (p < .05) compared with the other organs, regardless of the inoculum size. The liver and the lung of the liposomal cefoxitin-treated group showed significantly lower numbers of E. coli (5.0 x 10(4) and 6.3 x 10(2), respectively) compared with the untreated (liver, 6.3 x 10(7); lung, 2.0 x 10(6)) and free 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 nontreated septic group was significant (p < .05). No growth was observed from blood cultures taken 24 h after sepsis induction. All control experiments yielded negative cultures. The results of these experiments demonstrated that liposomal cefoxitin exerts an enhanced bactericidal effect in liver and lungs during Gram-negative sepsis.
Soltes
S
S
Center for Infection and Biomaterials Research, Toronto Hospital, Ontario, Canada.
Mustard
R A
RA
Shek
P N
PN
Florio
E
E
Bohnen
J M
JM
Mittelman
M W
MW
D000704:Analysis of Variance; D000818:Animals; D002440:Cefoxitin / Q000008:administration & dosage / Q000494:pharmacology*; D002513:Cephamycins / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000187:drug effects* / Q000302:isolation & purification; D008081:Liposomes; D008297:Male; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013552:Swine
D002513:Cephamycins; D008081:Liposomes; D002440:Cefoxitin