Effects of Different Types and Combinations of Antimicrobial Agents on Endotoxin Release from Gram-negative Bacteria: An In-Vitro and In-Vivo Study

Abstract

Total and free endotoxin release in time from cultures of Escherichia coli by different antibiotics was studied in vitro for 4 h in relation to the antibiotic effect on viable counts and morphological features of the test cultures. The most rapid fall in viable counts was seen after treatment with imipenem or the combination of imipenem with tobramycin, accompanied by an early, but minimal increase (1.8-fold) of the total (free plus cell-bound) endotoxin level at 1 h. Total endotoxin levels increased approximately 5-fold upon incubation with ceftazidime, tobramycin or the combination of tobramycin with cefuroxime, whereas incubation with cefuroxime or aztreonam alone caused a late 22-and 49-fold increase in total endotoxin, respectively, at 4 h. In chloramphenicol treated cultures there was still an increase in viable counts during therapy, resulting in an ultimately 78-fold increase of mean levels of total endotoxin. Free endotoxin levels increased approximately 6-fold within 1 h upon treatment with imipenem, alone or in combination with tobramycin, or ceftazidime as the result of rapid lysis of bacteria. Treatment with cefuroxime or aztreonam induced a relatively late but much higher release of free endotoxin (118-and 222-fold, respectively), which was due to the formation of long filamentous structures during the first 2 h of incubation and eventually cell lysis. Both tobramycin and the combination of tobramycin with cefuroxime caused a more gradual rise in free endotoxin, with a +/- 15-fold increase in free endotoxin at 4 h. In chloramphenicol treated cultures, as in the control cultures, the level of free endotoxin remained proportional to the amount of viable organisms. We also studied plasma endotoxin levels in 20 patients with septic shock. 10 out of these 20 patients had a detectable endotoxemia (greater than 5 ng/l) on admission. We describe the patterns of plasma endotoxin in these patients during the first 24 h of antibiotic treatment. We conclude that, in the in-vitro study, values of total endotoxin, free endotoxin, and the rate of release of endotoxin varies with the antibiotic used. We also demonstrate that in patients under treatment for septic shock endotoxin release can be related to the administration of antibiotics.

TLR4 Signaling Is Coupled to SRC Family Kinase Activation, Tyrosine Phosphorylation of Zonula Adherens Proteins, and Opening of the Paracellular Pathway in Human Lung Microvascular Endothelia

“…Since LPS associates with circulating lipoproteins (54), is rapidly cleared by the reticuloendothelial system (55), and nonspecifically inserts itself into lipid membranes, these levels may understate the levels of LPS presented to the host. LPS is continuously shed from the outer membranes of rapidly proliferating bacteria, and this release can be further increased up to ϳ200-fold through antibiotic-induced bacterial lysis (56,57). During endotoxemia, the endothelium responds not only to LPS itself but, simultaneously, to numerous endogenous mediators, such as TNF-␣, interleukin (IL)-1␤, interferons, and others (8 -10).…”

Antibiotic‐induced endotoxemia in a patient with endogenous endophthalmitis

“…5). Dofferhoff et al (1991) and Jackson et al (1992) have reported the effects of antibiotic treatment on the release of endotoxin by gram-negative bacteria. They have reported that the high levels of endotoxin with treatment with b-lactamase inhibitors of cephem antibiotics are the result of the formation of long filaments with late lysis, because these antibiotics bind to both penicillin-binding proteins (PBP)-1 and PBP-3 and produce lysis as well as filamentous changes.…”

The physico‐chemical characteristics of the phosphocholine‐containing glycoglycerolipid MfGL‐II govern the permeability properties of Mycoplasma fermentans

“…These results indicate that the samples form a gel phase at 25 and 35 8C and a lamellar liquid crystalline (L a ) phase at 45 and 55 8C (see below). 31 P NMR spectra recorded from samples with water contents of 50, 70, 90, and 95% (w/w) also indicate that a transition between a gel phase and an L a phase occurs between approximately 35 8C and 45 8C. In addition, these spectra exhibit two narrow signals which originate from lipid aggregates undergoing isotropic motional averaging (Fig.…”

“…31 P NMR spectra were obtained at 162.13 MHz using a Hahn echo pulse sequence with extended phase cycling [12]. Protons were decoupled during the data acquisition using the WALTZ decoupling scheme [13].…”