Liposomal cefoxitin in a porcine model of intra-abdominal sepsis: hemodynamic changes.
The effects of free versus liposomal cefoxitin on various physiological parameters in a porcine model of Gram-negative intra-abdominal sepsis were evaluated. Four different doses of Escherichia coli inoculum mixed with sterile pig feces were used (10(8), 10(9), 10(10), and 10(11) cfu/animal), and the most consistent hemodynamic changes were observed with an inoculum of approximately 10(11) bacteria/20 kg animal. Two treatment groups were established as follows: free cefoxitin (n = 9) and liposomal cefoxitin (n = 9). All animals were maintained under anesthesia for the duration of the study, and then euthanized 24 h following intra-abdominal inoculation. The inoculated and nontreated animals showed increases in heart rate, mean pulmonary arterial pressure, systemic and pulmonary vascular resistance, and decreases in mean systemic arterial pressure and cardiac index. These changes were significant (p < .05) compared with a control group injected with normal saline. Liposomal cefoxitin-treated animals showed significantly lower decreases in mean systemic arterial pressure and increases in heart rate (p < .05) compared with both the inoculated nontreated and free cefoxitin-treated groups. Both liposomal and free cefoxitin significantly modulated the mean pulmonary arterial pressure compared with the inoculated nontreated animals (p < .05). Acidosis that developed during intra-abdominal infection diminished 6 h following the first dose of liposomal cefoxitin (p < .05). The results of these experiments demonstrate that liposomal cefoxitin exerts a beneficial modulation of some of the hemodynamic disturbances during intra-abdominal Gram-negative sepsis.
Soltes
S
S
Centre for Infection and Biomaterials Research, Toronto Hospital, Ontario, Canada.
Shek
P N
PN
Mustard
R A
RA
Soric
I
I
Bohnen
J M
JM
Mittelman
M W
MW
D000005:Abdomen; D000818:Animals; D016470:Bacteremia / Q000188:drug therapy* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002440:Cefoxitin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004337:Drug Carriers; D004927:Escherichia coli Infections / Q000188:drug therapy* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008081:Liposomes; D008297:Male; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects
D004337:Drug Carriers; D008081:Liposomes; D002440:Cefoxitin