Related Experiment Video
Updated: Mar 24, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
Published on: August 30, 2018
Low-dose polymyxin: an option for therapy of Gram-negative sepsis
Stephan Harm1, Franz Gabor2, Jens Hartmann3
1Department for Health Sciences and Biomedicine, Danube University Krems, Krems, Austria Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria stephan.harm@donau-uni.ac.at.
Abstract:
Endotoxins are the major components of the outer membrane of most Gram-negative bacteria and are one of the main targets in inflammatory diseases. The presence of endotoxins in blood can provoke septic shock in case of pronounced immune response. Here we show in vitro inactivation of endotoxins by polymyxin B (PMB). The inflammatory activity of the LPS-PMB complex in blood was examined in vitro in freshly drawn blood samples. Plasma protein binding of PMB was determined by ultracentrifugation using membranes with different molecular cut-offs, and PMB clearance during dialysis was calculated after in vitro experiments using the AV1000S filter. The formed LPS-PMB complex has lower inflammatory activity in blood, which results in highly reduced cytokine secretion. According to in vitro measurements, the appropriate plasma level of PMB for LPS inactivation is between 100 and 200 ng/ml. Furthermore, the combination of cytokine removal by adsorbent treatment with LPS inactivation by PMB dosage leads to strong suppression of inflammatory effects in blood in an in vitro model. Inactivation of endotoxins by low-dose intravenous PMB infusion or infusion into the extracorporeal circuit during blood purification can be applied to overcome the urgent need for endotoxin elimination not only in treatment of sepsis, but also in liver failure.
Insights
Polymyxin B (PMB) effectively inactivates endotoxins (lipopolysaccharides) in vitro, reducing their inflammatory potential in blood. This endotoxin inactivation, combined with cytokine removal, shows promise for treating sepsis and liver failure.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Endotoxins, components of Gram-negative bacteria, trigger severe immune responses like septic shock.
- Current treatments for endotoxin-related conditions are limited.
Purpose of the Study:
- To investigate the in vitro inactivation of endotoxins by polymyxin B (PMB).
- To assess the inflammatory activity of the lipopolysaccharide-PMB complex in blood.
- To determine optimal PMB levels for endotoxin inactivation.
Main Methods:
- In vitro inactivation of endotoxins using PMB.
- Examination of LPS-PMB complex inflammatory activity in human blood.
- Measurement of PMB plasma protein binding and clearance during dialysis.
- Assessment of cytokine secretion and inflammatory markers.
Main Results:
- The LPS-PMB complex exhibited significantly reduced inflammatory activity in vitro.
- Optimal plasma PMB levels for endotoxin inactivation were determined to be 100-200 ng/ml.
- Combined PMB treatment and cytokine removal strongly suppressed inflammatory effects in an in vitro model.
Conclusions:
- PMB effectively inactivates endotoxins, reducing their inflammatory impact in blood.
- Low-dose intravenous PMB or extracorporeal infusion shows potential for endotoxin elimination in sepsis and liver failure.
- Combining endotoxin inactivation with cytokine removal offers a potent strategy against inflammatory diseases.
More Related Videos
Related Concept Videos
Acute Pyelonephritis II: Diagnostic Studies and Management
Inhibitors of Gram-positive Cell Wall Synthesis
Pharmaceutical Alternatives: Stability-Related Therapeutic Nonequivalence
Inhibitors of Bacterial Protein Synthesis
Combined Effects of Drugs: Synergism
Such synergistic combinations...
Determination of Multiple Dosing Parameters: Steady-State, Minimum and Maximum Concentrations

