Volume 11 Supplement 4

Sepsis 2007

Open Access

Microbial metabolites in the blood of patients with sepsis

  • Anastasia Khodakova1 and
  • Natalia Beloborodova1
Critical Care200711(Suppl 4):P5

https://doi.org/10.1186/cc5984

Published: 26 September 2007

Background

Molecular mechanisms of the pathophysiology of sepsis remain unknown. Preliminary results allow one to suppose that investigation of biological effects of microbial metabolites, particularly aromatic acids, is one of the most promising methods in elucidation of the problem. These compounds can be produced during microbial fermentation of aromatic amino acids. But little is known of which microorganisms participate in such processes. The aim was to assess the comparative level of aromatic acids in serum of cardiosurgical patients with documentary sepsis and to clarify the 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 of investigation consisted of 12 cardiosurgical patients with documentary sepsis, with mortality of 42% (5/12). The comparison groups were: 16 clinically healthy volunteers, 36 patients with acquired heart diseases before surgery, nine patients with smooth recovery on the third day after surgery, 10 patients 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 and C. parapsilosis were isolated from the blood of cardiosurgical patients and identified. Concentrations of aromatic acids were determined by gas chromatography–mass spectrometry. Data were compared by Mann–Whitney U-test, P < 0.05 considered significant.

Results

Significant differences were observed among the groups (Table 1). 3-Phenylpropionic and 1-indolacetic acids were found to be prevalent in groups of healthy volunteers and patients before surgery. Increased levels of phenyllactic acid (PLA), p-hydroxyphenylacetic acid (HPAA), p-hydroxyphenyllactic acid (HPLA) and 3-indolacetic acid were revealed in the group of sepsis compared with other groups. Moreover, the highest concentrations of PLA, HPAA and HPLA were in serum of nonsurvivors (n = 5) compared with survivors (n = 7): PLA, 1,651 (656–1,959) versus 233 (122–360) ng/ml, P = 0.02; HPAA, 5,976 (2,689–6,667) versus 1,108 (461–2,121) ng/ml, P = 0.02; HPLA, 3,313 (2,409–6,098) versus 564 (446–718) ng/ml, P = 0.005. Gas chromatography–mass spectrometry analysis of spent growth medium showed that Gram-negative enterobacteria produced increased amounts of PLA and HPLA acids. Particularly, K. pneumonia had the highest level of acids PLA = 100 r.u. (r.u. – the ratio of substance content in sample to uninoculated media) and HPLA = 60 r.u., E. coli had PLA = 35 r.u. and HPLA = 20 r.u., and S. marcesceus and E. cloacae had PLA = 4 r.u. and HPLA = 6 r.u. The culture of Gram-positive cocci produced increased level of the same acids, for S. aureus PLA = 20 r.u. and HPLA = 17 r.u., and for S. epidermidis PLA = 6 r.u. and HPLA = 3 r.u., except for E. faecalis, which had the only PLA = 6 r.u. Gram-negative nonfermented bacteria produced increased levels of 1-indolacetic acid and 3-indolacetic acid, but no PLA and HPLA. The level of aromatic acids in the medium after cultivation of fungi was equal to control.
Table 1

Concentration of aromatic acids in serum sepsis patients and subjects of comparison groups

Aromatic acid (ng/ml)

Patients with sepsis (n = 12)

Volunteers (n = 16)

Patients before surgery (n = 36)

Patients with smooth recovery (n = 9)

Patients with pneumonia (n = 10)

p-Hydroxyphenylacetic acid

2,140 (631–3,516)

72 (62–93)***

114 (53–220)***

263 (109–313)**

456 (344–667)*

3-Phenylpropionic acid

0

35 (20–54)**

4 (0–29)

0

0 (0–3)

Phenyllactic acid

367 (217–1,098)

47 (37–64)**

58 (37–93)**

89 (68–126)*

112 (89–177)*

p-Hydroxyphenyllactic acid

1,543 (564–2,731)

195 (159–371)***

254 (134–373)***

288 (269–772)*

465 (314–836)

1-Indolacetic acid

0

262 (113–385)***

47 (0–218)*

275 (228–499)***

0 (0–27)

3-Indolacetic acid

246 (183–628)

93 (56–141)*

181 (60–542)

57(30–74)*

231 (149–375)

Data presented as median (25th–75th percentile range). *P < 0.05, **P < 0.001, ***P < 0.0001, compared with sepsis patients.

Conclusion

Increased levels of PLA, HPAA and HPLA in serum patients with sepsis, especially with fatal outcome, are associated with development of infectious complications. 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.

Authors’ Affiliations

(1)
Bakulev Scientific Center for Cardiovascular Surgery

Copyright

© BioMed Central Ltd 2007

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