Endotoxin-neutralising effect and anti-inflammatory properites of tobramycin and ceftazidime in porcine endotoxic shock

Introduction

Administration of antibiotics represents a cornerstone in the treatment of severe bacterial infections. In addition to their antibacterial effect, antibiotics have been shown to cause other effects on the inflammatory response. Aminoglycosides have been considered to neutralise endotoxin and ceftazidime to modulate the inflammatory response by an antioxidative effect.

The primary aim of this study was to investigate whether endotoxin given as an infusion in a porcine model could be neutralised by the addition of tobramycin. The secondary endpoint was to study whether ceftazidime could affect the inflammatory response by modifying the cytokine release during the end of the study period.

Methods

Fourteen pigs were exposed to an endotoxin infusion of 4 μg/kg during 30 min followed by 1 μg/kg during the rest of the 6 hour experiment. Five of the animals were randomised to receive tobramycin 6 mg/kg, five were given ceftazidime 40 mg/kg, and four received saline solution.

Results

The endotoxin levels remained stable after 1 hour of the experiment and there was no difference between the treatment groups, thus indicating that there were no neutralising effects by any of the antibiotics. The plasma TNF-α levels reached peak values 1 hour after starting the endotoxin infusion, median value 7265 ng/l (2492–10,625 ng/l), and there were no significant differences in peak TNF-α or elimination rate between the treatment groups. Plasma IL-6 levels peaked after 2–3 hours with a median maximum IL-6 value of 2509 ng/l (1544–7854 ng/l). A significantly greater reduction of IL-6 was seen in the animals treated with ceftazidime or tobramycin compared with those receiving saline (P < 0.05). In the ceftazidime group also, absolute values obtained at 6 hours were significantly lower than the corresponding values in the saline group (P < 0.05).

Conclusion

Endotoxin was not neutralised by tobramycin or ceftazidime in this porcine model. However, data indicate a slight anti-inflammatory effect of ceftazidime and perhaps also of tobramycin as measured by the reduction in IL-6.