Acute administration of antibiotics modulates intestinal capillary perfusion and leukocyte adherence during experimental sepsis

Abstract

Antibiotic treatment represents a mainstay of therapy for clinical sepsis. Distinct from their antimicrobial effects, antibiotics may impact the inflammatory process in sepsis, e.g. within the intestinal microcirculation. The impact of seven antibiotics relevant to clinical sepsis on intestinal leukocyte recruitment and capillary perfusion was studied in rats with colon ascendens stent peritonitis (CASP)-induced sepsis or after endotoxin [lipopolysaccharide (LPS)] challenge. The following antibiotics were included: daptomycin; erythromycin; imipenem; linezolid; tigecycline; tobramycin; and vancomycin. The number of rolling and adherent leukocytes in intestinal submucosal venules and the functional capillary density (FCD) in three layers of the intestinal wall were assessed using intravital microscopy. CASP-induced sepsis reduces the intestinal FCD by 30-50%. Single administration of daptomycin, tigecycline or linezolid increased the intestinal FCD. CASP sepsis increased the number of rolling leukocytes by 4.5-fold, which was reduced by erythromycin but increased by vancomycin. The number of adherent leukocytes increased 3-fold in rats with CASP sepsis. It was reduced following administration of daptomycin, tigecycline (in V1 and V3 venules), erythromycin and linezolid (in V1 venules). However, following tobramycin and vancomycin, leukocyte adhesion was further enhanced. Administration of tigecycline and linezolid reduced the LPS-induced increase in the number of adherent leukocytes by 50%. However, imipenem did not affect leukocyte adherence. In conclusion, this work highlights the beneficial impact of the antibiotics daptomycin, tigecycline, erythromycin and linezolid in that they improve intestinal capillary perfusion and/or reduce leukocyte recruitment, whilst the antibiotics imipenem, tobramycin and vancomycin do not exert these properties.