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Antibiotic-related acute effects within the intestinal microcirculation in experimental sepsis

Introduction

Although the benefit of antibiotic therapy in infectious inflammatory diseases remains unquestioned [1], little is known about the effects of these antibiotics on the inflamed microcirculation independent of their antimicrobial property. The aim of this study was to evaluate acute effects related to antibiotics administration upon the intestinal microcirculation, which plays a crucial role in the pathogenesis of sepsis and subsequent multiorgan failure [2, 3].

Methods

Experimental sepsis was induced in 50 Lewis rats using the colon ascendens stent peritonitis model [4]. Four frequently used antibiotics were included in the study (20 mg/kg imipenem/cilastatin (IMI), 25 mg/kg tobramycin (TOB), 70 mg/kg vancomycin (VAN), 5 mg/kg erythromycin (ERY)). The antibiotics were administered as a single intravenous bolus following 16 hours of observation time. The intestinal functional capillary density and leukocyte–endothelial interactions were evaluated using intravital microscopy 1 hour following antibiotic treatment. Additional experiments were performed in an abacterial setting with comparable microcirculatory disturbances (2 hours endotoxemia; n = 50).

Results

Acute IMI or TOB administration, respectively, did not affect the intestinal microcirculation. VAN treatment aggravated the leukocyte rolling behavior in this acute setting. In contrast, ERY administration significantly reduced leukocyte activation and improved the functional capillary density within the intestinal microcirculation during experimental sepsis. These effects could be confirmed during endotoxemia, suggesting that ERY exerts anti-inflammatory effects in addition to its antibacterial action.

Conclusion

When choosing antimicrobial agents in septic conditions, possible effects of the antibiotics within the pathogenetically important intestinal microcirculation should be considered. In conjunction with microbial sensitivity tests, the results of such studies assist in selecting the appropriate antibiotic therapy.

References

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Lehmann, C., Bac, V., Richter, J. et al. Antibiotic-related acute effects within the intestinal microcirculation in experimental sepsis. Crit Care 12, P56 (2008). https://doi.org/10.1186/cc6277

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Keywords

  • Vancomycin
  • Tobramycin
  • Intravital Microscopy
  • Leukocyte Rolling
  • Functional Capillary Density