Summary auto-generated
This in vitro study examined how four antibiotics affect endotoxin (lipopolysaccharide) release from gram-negative bacteria Enterobacter cloacae and Escherichia coli. Researchers exposed bacterial cultures to cefotaxime, ciprofloxacin, piperacillin, and tobramycin at bactericidal concentrations, then measured endotoxin release using a limulus amoebocyte lysate assay and confirmed results with silver-stained SDS-PAGE analysis. They also examined bacterial morphology using scanning electron microscopy. Cefotaxime, ciprofloxacin, and piperacillin caused significant endotoxin release within 1-2 hours, correlating with visible cell wall damage including filamentation and lysis. In contrast, tobramycin produced minimal endotoxin release with no observable morphological changes. The findings suggest that different antibiotics have markedly different effects on endotoxin release. This has clinical implications for sepsis treatment, as excessive endotoxin release during antibiotic therapy could worsen endotoxin-related shock. The study concludes that tobramycin may be preferable for treating gram-negative sepsis due to its bactericidal activity combined with its lack of propensity to trigger dangerous endotoxin release.
Key findings
- Cefotaxime, ciprofloxacin, and piperacillin caused rapid and significant endotoxin release from E. cloacae and E. coli, reaching approximately 400 EU/ml within 3 hours
- Tobramycin did not significantly increase endotoxin release compared to untreated control cultures despite equivalent bactericidal activity
- Endotoxin release correlated with antibiotic-induced morphological changes: filamentation and cell lysis with beta-lactams and fluoroquinolones, but no morphological changes with tobramycin
- Tobramycin's lack of cell wall destructive effects appears to retain endotoxin within the bacterial cell rather than releasing it into the medium
- These findings suggest tobramycin may be the preferred antibiotic for treating gram-negative sepsis to avoid exacerbating endotoxin-mediated shock
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Abstract
The ability of cefotaxime, ciprofloxacin, piperacillin and tobramycin to cause release of endotoxin was examined in vitro with cultures of Enterobacter cloacae and Escherichia coli. Endotoxin was measured by a quantitative limulus amoebocyte lysate assay and its presence was confirmed by silver staining of the lipopolysaccharide moiety following SDS-PAGE. The morphology of the bacteria during antibiotic exposure was examined by scanning electronmicroscopy. Cefotaxime, ciprofloxacin and piperacillin caused significant endotoxin release, correlating with their ability to affect cell-wall morphology, causing filamentation, wall breakage and cell lysis. In contrast, little endotoxin was released when bacteria were exposed to tobramycin and no morphological changes were observed when bacteria were exposed to bactericidal concentrations of this aminoglycoside. Its antimicrobial spectrum and bactericidal activity make tobramycin an appropriate agent for treatment of sepsis caused by gram-negative bacteria and its lack of propensity to elicit excessive release of endotoxin may avoid exacerbation of endotoxin-related shock in sepsis.