Microbial metabolites in the blood of patients with sepsis

1. Microbial metabolites in the blood of patients with sepsis SEPSIS 2007Paris, France September 27-29, 2007 P 5 A. Khodakova, N. Beloborodova Bakoulev Scientific Center for Cardiovascular Surgery, Moscow, Russia Background Molecular mechanisms of pathophysiology of sepsis are remained unknown. Preliminary results allow to suppose that investigation of biological effects of microbial metabolites, particularly aromatic acids, is one of the most promising way in elucidation of the problem [1, 2].The aim was to assess the comparative level of aromatic acids in serum of cardiosurgical patients (pts.) with documentary sepsis and to clarify in vitro metabolic profile of aromatic acids in spent growth medium of main clinical blood isolates. Materials and Methods Serum samples were collected from 83 adult subjects (mean age 52 (42-58) years). The main group was consisted of 12 cardiosurgical pts. with documentary sepsis, with mortality 42% (5/12). The comparison groups were: 16 clinically healthy volunteers, 36 pts. with acquired heart diseases before surgery, 9 pts. with smooth recovery on the 3d day after surgery, 10 pts. with pneumonia after surgery. The cultures (n=32) of S.aureus, S.epidermidis, E.faecalis, K.pneumonia, S.marcesceus, E.coli, E.cloacae, A.baumanii, P.aeruginosa, C.albicans, C.parapsilosis were isolated from the blood of cardiosurgical pts. and identificated. Concentrations of aromatic acids were determined by gas chromatography-mass spectrometry (GC-MS, Agilent 6890/5973, AgilentTechnologies, USA). Data were compared by Mann-Whitney U-test, p-values less than 0.05 were considered significant. Results Significant differences were observed among the groups. 3-Phenylpropionic and 1-indolacetic acids were found to be prevalent in groups of healthy volunteers and pts. before surgery. Increased levels of phenyllactic (PLA), p-hydroxyphenylacetic (HPAA), p-hydroxyphenyllactic (HPLA) and 3-indolacetic acids (3IAA) were revealed in group of sepsis compared with other groups (Table 1). Moreover, the highest concentrations of PLA, HPAA, HPLA were in serum of non-survivors compared to survivors. p=0.02 p=0.005 p=0.02 Concentrations of PLA, HPAA, HPLA in serum of survivors and non-survivors pts. with sepsis Table 1. Concentration of aromatic acids in serum sepsis patients and subjects of comparison groups. Commentary: 1. Data are given as median (range of 25th and 75th percentiles); 2. * p<0.05; ** p<0.001; *** p<0.0001 compared with sepsis patients. GC-MS analysis of spent growth medium showed that gram(-) enterobacteria produced increased amount of PLA and HPLA. The culture of gram(+) cocci produced increased level of the same acids, except for E.faecalis, which had the only PLA=6r.u. (r.u. - the ratio of substance content in sample to uninoculated media). Gram(-) non-fermented bacteria produced increased levels of 3IAA. The level of aromatic acids in the medium after cultivation of fungi was equal to control. Conclusions Increased level of PLA, HPAA, HPLA in serum pts. with sepsis, especially with fatal outcome, are associated with development of infectious complication. These compounds are produced by clinically important bacteria, such as K. pneumonia> E. coli> S.aureus> S.marcesceus, E.cloacae, S.epidermidis, but not by fungi. The results can denote biological activity of these microbial metabolites and their influence on pathogenesis of sepsis. • References • Beloborodova N.V., Arkhipova A.S.et al - Chromatographic mass spectrometric determination of low-molecular-weight aromatic compounds of microbial origin in the serum from patients with sepsis. - Klin Lab Diagn. - 2006 Feb;(2):3-6. • Scalbert A. et al. - Dietary polyphenols and the prevention of diseases. - Crit Rev Food Sci Nutr. - 2005;45(4):287-306