Antibiotic-induced release of endotoxin in chronically bacteriuric patients

Abstract

A novel in vivo model for the study of antibiotic-induced release of endotoxin from gram-negative bacteria is described. The model uses the chronically colonized urinary tracts of patients whose spinal cords have been injured. At baseline, the organisms were present in the range of 1 x i03 to 2 x i07 CFU/ml, and the concentration of endotoxin ranged from 2 x 10-1 to 1 x 103 ng/ml in 44 studies. tion. The intention of the studies was to develop a novel model for the study of antibiotic action in vivo, with the purpose of comparing antibiotics which differ in their modes of antibacterial activity. In each study, the effects on endotoxin concentration, which were determined by using a novel kinetic Limulus amoebocyte lysate (LAL) assay (16-18) and bacterial viability, were monitored. The reason for performing these studies in patients with spinal cord injuries is that because of their neurogenic injury, their urinary tracts are dilated and, hence, could be expected to resemble the chemostat culture apparatus. MATERIALS AND METHODSStudy design. The Austin Hospital, where these studies were performed, is a referral center for patients with spinal injuries for southeastern Australia. The study was approved by the Austin Hospital Ethics Review Committee.A total of 44, studies were performed on 11 volunteer patients who had given informed consent. Each study consisted of repeated samplings of urine for up to 3 h after administration of 6 mg of furosemide intramuscularly at time -20 min, followed by antibiotic (or no treatment) at time zero. In each patient, the individual studies were separated by a minimum interval of 3 days and a maximum interval of 14 days.Volunteer patients were selected from the spinal cord injury rehabilitation ward by the following criteria: an indwelling urinary catheter was present, the most recent routine weekly catheter urine culture revealed the growth of not more than two different gram-negative bacteria, and in the previous 7 days the patient had not been treated with either antibiotics or urinary antiseptics. The study period lasted for up to 4 weeks. Patients were suspended from the study if, during that time, therapy with antibiotics or urinary antiseptics was commenced.

Antibiotic-Induced Lipopolysaccharide (LPS) Release fromSalmonella typhi: Delay between Killing by Ceftazidime and Imipenem and Release of LPS

“…The remaining question is whether and to what extent antibiotic-induced LPS release and subsequent induction of cytokine production aggravate the clinical symptoms of septic shock. A number of clinical studies have addressed this issue but have yielded contradictory results (4,10,16,20). In this respect, it is important to realize that the endotoxin concentration in blood is not the only factor determining the severity of septic shock caused by gram-negative bacteria.…”