Distribution of free and liposomal cefoxitin in plasma and peritoneal fluid in a porcine intra-abdominal sepsis model.

The plasma and peritoneal fluid pharmacokinetic parameters obtained after the intravenous administration of free and liposomal cefoxitin were studied in a porcine model of intraabdominal sepsis. No prior assumptions were made to predict the number of compartments pertaining to drug clearance from the administration of either cefoxitin formulation. The experimental data obtained were applied to fit mathematical models of multiexponential drug clearance and the pharmacokinetic data were found to best fit a two-compartment open model. Liposomal encapsulation significantly altered the plasma drug distribution pattern resulting in changes in the magnitude of a number of pharmacokinetic parameters examined. The mean post-distributive half-life of liposomal cefoxitin was substantially longer than that of free cefoxitin by at least 3 times. The peritoneal cavity appeared to provide a reservoir for the initial distributive phase of rapid drug clearance from the plasma compartment followed by a less-rapid post-distributive phase. The cumulative drug level, as determined by the area under the concentration curve (AUC) as a function of time, in the plasma of animals treated with liposomal cefoxitin was about 3-4 fold as high as that of animals treated with free cefoxitin. The differences in pharmacokinetic parameters appeared to account for the improved therapeutic efficacy of liposomal cefoxitin in this animal model.

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.

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.

The otolaryngologic manifestations of malignant lymphoma with a high content of epithelioid histiocytes (Lennert's lymphoma).

Malignant lymphoma with a high content of epithelioid histiocytes is a rare non-Hodgkin lymphoma first described by Lennert and Mestdagh (Lennert's lymphoma) in 1968. Distinguishing characteristics include frequent involvement of the nasopharynx, Waldeyer's ring, and cervical lymph nodes. Of the four patients included in this report, three had Waldeyer's ring involvement and four had cervical lymphadenopathy. Our experience and that of others demonstrate the unpredictable and variable course of the disease, as well as the inconsistent response to various therapeutic modalities; especially interesting is the remission obtained in one patient treated with corticosteroids alone, in contrast to the others who followed a rapid downhill course to death in spite of (or as a complication of) chemotherapy and radiation. The role of the otolaryngologist in the diagnosis and management of the disease is emphasized.