Endotoxin Testing

Testing Within ANSI/AAMI ST108:2023 and Beyond 

Endotoxins are the lipid A component of lipopolysaccharides (LPS) found in the cell wall outer membrane of Gram-negative bacteria.  It is typically shed by the bacterium during periods of rapid growth or as a byproduct of death and cell lysis.  Endotoxins are not a pathogen, but a component of a bacterium that when present in the body are recognized by TLR4 receptors on host immune cells and trigger a rapid protective inflammatory response in the host against an invading pathogen.  These inflammatory steps are also linked to the more targeted specific immune response against the pathogen, ensuring rapid and complete elimination of the threat.   Because the inflammatory processes can be damaging to the host, the steps in triggering inflammation are usually  tightly controlled against over-reaction and are rapidly down-regulated once the threat has been neutralized.

The magnitude and time-course (i.e. acute vs chronic) of an inflammatory response varies depending on the endotoxin chemistry, the pathogenic properties of the bacteria from where it originated, the size of bacterial population, and the location of the infection (i.e. local in the tissue vs. systemic in the bloodstream).  Bloodstream infections with bacteria are the most serious threat, and often result in an over-reaction by the body, triggering systemic inflammation in the bloodstream where high inflammation is poorly tolerated.  Severe bloodstream (systemic) inflammation leads to a life-threatening sepsis and endotoxin shock, causing a body-wide capillary bed vasodilation with increased vascular permeability, and associated with a rapid drop in blood pressure, disseminated intravascular coagulation with amputations, multi-organ failure, and death.   However, even low levels of endotoxins can trigger acute inflammation in patients, thus the need for the ST108 water quality standard for these applicable clinical situations.

It is important to understand that gram-negative bacteria and their endotoxins can be present in a potable water system (whether from the facility’s utility water or reverse osmosis systems).  Some of these microorganisms can form biofilms that promote endotoxin shedding into systems and offer protection from biocides. Controlling these microorganisms and potential biofilm formation is an important factor in reducing endotoxin exposure. The Association of the Advancement of Medical Instrumentation (AAMI) in conjunction with the ISO have developed the following guidelines for medical device reprocessing and dialysis water: