Are phenylcarboxylic acids really markers in severe sepsis?

Introduction

Laboratory diagnostics of sepsis need to be improved. There is no evidence in the literature whether microbial metabolites could be used as sepsis markers. As a result of large-scale screening of microbial compounds we showed that levels of some phenylcarboxylic acids (PCAs) were increased in blood of septic patients. The content of p-hydroxyphenyllactic acid (HPLA), phenyllactic acid (PLA) and p-hydroxyphenylacetic acid (HPAA) was significantly higher in blood of patients with severe sepsis compared with control groups. The aim of the present study is to evaluate the sensitivity and specificity of PLA, HPLA and HPAA as markers for severe sepsis diagnostics.

Methods

In total, 264 blood samples from 200 adults were included to research. All persons were divided into groups with infectious complications after cardiosurgery (35 severe sepsis, 35 local infection complication) and others (33 non-infection complication after surgery, 30 smooth recovery after surgery, 42 before surgery and 25 healthy volunteers). Clinical characteristics and procalcitonin (PCT) a well established biomarker of sepsis were assessed in all patients. Severe sepsis was diagnosed according to consensus criteria, also a level of PCT ≥2 ng/ml was an additional criterion. Blood concentrations of PCAs were determined by gas chromatography-mass spectrometry.

Results

The levels of PCA in two control groups (healthy people and patients before surgery) were HPAA 0.4 to 0.8 × 10^-6 M, HPLA 1.2 to 1.5 × 10^-6 M, PLA 0.3 to 0.4 × 10^-6 M and were not significantly different. Otherwise the levels of HPAA, HPLA and PLA as 11.6 (3.3 to 33.6) × 10^-6 M, 7.5 (3.0 to 14.4) × 10^-6 M and 1.8 (1.1 to 4.9) × 10^-6 M in all severe sepsis patients were significantly increased versus control groups and versus all other groups (P < 0.0001). In addition the levels of PCAs from surviving and nonsurviving severe sepsis patients were compared with each other. Nonsurviving sepsis patients had a significantly higher content of PLA (3.6 (1.5 to 6.4) × 10^-6 M vs. 1.2 (0.8 to 1.6) × 10^-6 M for survivors); the same trend was observed for HPLA (12.5 (5.6 to 34.7) × 10^-6 M vs. 2.8 (2.2 to 5.0) × 10^-6 M correspondingly), but not for HPAA.

Conclusion

The following levels of PCAs are appropriate for diagnostic of sepsis: HPAA 8 × 10^-6 M (sensitivity 64.3%, specificity 88.9%), HPLA 3 × 10^-6 M (sensitivity 75%, specificity 66.4%), PLA 1 × 10^-6 M (sensitivity 75%, specificity 71.6%). Obtained data indicate that quantitative measurement of PLA, HPLA and HPAA in blood could be used for sepsis diagnostics in clinical practice and also as a predictor of outcome in high-risk surgery.