Tag Archives: FD-1080

He effects of metronidazole (MET), imipenem (IMI), tobramycin (TOB) and vancomycin

He effects of metronidazole (MET), imipenem (IMI), tobramycin (TOB) and vancomycin (VAN) on the intestinal microcirculation in septic rats using intravital microscopy (IVM), on the release of the cytokines TNF-, IL-1, IL-6 and IL-10, and on the in-vitro reactivity of the rat aorta. Methods We induced sepsis in the animals (Lewis rats) using the Colon Ascendens Stent Peritonitis (CASP) model. MET (10 mg/kg), IMI (20 mg/kg), TOB (25 mg/kg) and VAN (70 mg/KG) were given intravenously 16 hours following sepsis induction. Intravital microscopic examination was performed 2 hours later. Cytokine release was estimated at the end of the experiments. Direct effects of the antibiotics on vascular tonus were studied in normal rat aortal rings in-vitro precontracted either with phenylephrine (PE) (5 ?10? M) or 20/40 mM KCl. Results In the CASP model we observed a reduced functional capillary density in the muscular and mucosal layers of the intestine and an increased number of temporary and firmly adhering leukocytes in submucosal venules. Acute treatment with MET attenuated this response. TNF- release in untreated CASP animals was twice as high as compared with MET-treated animals. In vitro, higher concentrations (up to 10? M) of some antibiotics produced moderate relaxation: TOB 47 (PE), VAN 44 (PE), MET 48 (20 mM KCl). Conclusion Antibiotics may exert, in addition to their antimicrobial action, effects on the microcirculation, PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/2805811 and potentially could influence vascular (hypo)reactivity in septic conditions.production of mediators of the systemic inflammatory response syndrome [1]. Previous studies suggested an association of TNF and LTA SNPs and the incidence of sepsis among ICU patients [2-4]. By examining several candidate genes (TNF, PAI-1, IL-1, IL-6), previously reported to be associated with sepsis outcome in our cohort [5,6], we now report that genetic variation in TNF and/or LTA is predictive for the development of sepsis in multiple trauma patients with a low prevalence of other clinically confounding factors. Patients and methods One hundred and fifty-nine multiple trauma patients were included prospectively following admission to the ICU with an ISS of 12 points or more after complete assessment of injuries. We genotyped all known SNPs including those in the 5 region of the TNF gene, including LTA, with a reported allele frequency of the rare allele of greater than 5 in Caucasians (n = 9 SNPs). Univariate analysis and multivariate logistic regression analysis were performed. Results Seventy-two patients (45.3 ) fulfilled the criteria for sepsis after severe trauma and 32 PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/16266907 (38.9 ) patients died from a sepsis leading to MOF. Allele distributions were according to the HW equilibrium. A significant association for the incidence of sepsis after multiple trauma was observed for the TNF ?08A allele (OR 7.14; 95 CI, 3.1?6.45; P < 0.0001), and the completely linked LTA +252G allele (OR 1.96; 95 CI, 1.02?.78; P < 0.042). Additionally, both alleles showed BNTA significant association with death after severe trauma (TNF ?08A: OR 7.65; 95 CI, 13.27?7.93; P < 0.0001; LTA +252G: OR 5.58; 95 CI, 2.02?5.44; P < 0.0002). Conclusion The presence of one or two copies of the TNF ?08A, LTA +252G haplotype is strongly predictive for the incidence of sepsis and death in multiple trauma patients. References 1. Menges et al.: Crit Care Med 1999, 27:733-740. 2. Mira et al.: JAMA 1999, 282:561-568. 3. Rauchschwalbe et al.: J Trauma 2004, 56:815-822. 4. Stuber et.