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Antibiotic-induced release of endotoxin: in-vitro comparison of meropenem and other antibiotics
M Trautmann1, R Zick, T Rukavina
1Department of Medical Microbiology and Hygiene, University of Ulm, Germany.
Abstract:
The influence of meropenem, a new carbapenem antibiotic, on cell morphology and in-vitro lipopolysaccharide (LPS) release from Escherichia coli was compared with that of imipenem, ceftazidime, tobramycin and ciprofloxacin. Free and cell-associated LPS was quantified by means of a capture ELISA method based on the recognition of E. coli LPS by monoclonal antibodies. Microscopically, meropenem was found to induce spheroplast formation similar to that seen with imipenem, while ceftazidime and ciprofloxacin induced filament formation. Free and cell-associated LPS levels were low in the presence of meropenem, imipenem, ciprofloxacin and tobramycin, but high in the presence of ceftazidime. Reduced endotoxin release appears to be a common property of carbapenem antibiotics. Morphological changes in bacteria in the presence of antibiotics do not predict their LPS-liberating effect since ciprofloxacin induced low levels of LPS despite causing filament formation.
Insights
Meropenem and imipenem, carbapenem antibiotics, reduced bacterial lipopolysaccharide (LPS) release and caused spheroplast formation in Escherichia coli. This contrasts with ceftazidime, which increased LPS release.
Area of Science:
- Microbiology
- Pharmacology
- Immunology
Background:
- Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria, acting as an endotoxin.
- Antibiotic-induced bacterial lysis can release LPS, potentially exacerbating inflammatory responses.
- Carbapenem antibiotics are broad-spectrum agents with varying effects on bacterial structure and LPS release.
Purpose of the Study:
- To investigate the impact of meropenem on Escherichia coli cell morphology and LPS release.
- To compare meropenem's effects with other antibiotics: imipenem, ceftazidime, tobramycin, and ciprofloxacin.
- To determine if morphological changes correlate with LPS liberation.
Main Methods:
- Escherichia coli cultures were treated with meropenem, imipenem, ceftazidime, tobramycin, or ciprofloxacin.
- Bacterial cell morphology was assessed microscopically.
- Free and cell-associated LPS levels were quantified using a capture ELISA with monoclonal antibodies.
Main Results:
- Meropenem and imipenem induced spheroplast formation in E. coli.
- Ceftazidime and ciprofloxacin induced filament formation.
- Meropenem, imipenem, ciprofloxacin, and tobramycin resulted in low LPS levels, while ceftazidime showed high LPS levels.
Conclusions:
- Reduced endotoxin (LPS) release is a characteristic property of carbapenem antibiotics like meropenem.
- Antibiotic-induced morphological changes do not reliably predict LPS release; ciprofloxacin caused filamentation but low LPS release.
- Meropenem demonstrates a favorable profile regarding LPS liberation compared to ceftazidime.