Antimicrobial-induced endotoxin and cytokine activity in an in vitro model of septicemia in foals.

This research article investigates which antimicrobials minimally induce endotoxin release and inflammatory mediators when treating neonatal foals with septicemia caused by Escherichia coli. It finds that Aminoglycosides, such as Amikacin, induce less endotoxemia and TNF-alpha synthesis during treatment compared to beta-lactam antimicrobials.

Study Design and Methodology

• The study included blood samples from 10 healthy foals with Escherichia coli isolates A and B that were collected from two septicemic foals. They tested for the minimal inhibitory concentrations (MIC) of nine different types of antimicrobials.
• Five of these antimicrobials were further tested in vitro (in a controlled environment outside a living organism) at two and twenty times their respective MIC levels.
• The blood samples or mononuclear cells were grown in tissue-culture media along with 105 colony-forming units of E. coli and each antimicrobial or a saline solution.
• After incubation for six hours, the viable bacteria remaining were counted, and the endotoxin, as well as tumor necrosis, activity in the supernatant was then tested.

Results

• The testing of whole blood was complicated due to the bactericidal effects already present in the blood samples.
• In the mononuclear cell suspensions used, all tested antimicrobials effectively reduced the number of viable bacteria to low or virtually undetectable amounts. There was no significant difference in the bactericidal efficacy of the tested antimicrobials.
• Amikacin, whether used alone or combined with ampicillin, resulted in significantly less endotoxin activity than did ampicillin, imipenem, or ceftiofur when used independently.
• A correlational relationship was observed between TNF-alpha (a cell signalling protein involved in systemic inflammation) and endotoxin activity.

Conclusions

• The study concluded that Aminoglycosides, such as Amikacin, were less likely to induce endotoxemia (the presence of endotoxins in the blood which can cause a catastrophic immune response) and TNF-alpha synthesis during the bactericidal treatment of E. coli septicemia.
• This suggests that beta-lactam antimicrobials such as ampicillin, imipenem, or ceftiofur could potentially induce more endotoxemia and should therefore be used in conjunction with appropriate treatments for endotoxemia when treating septicemic neonatal foals.