Table 1.
Potential biomarkers for diagnosis of P. aeruginosa sepsis
| Pathway or source/metabolite | Relative peak intensities | P value ≤ 0.05 | AUC ≥ 0.96a | Included in the set of 26 | |
|---|---|---|---|---|---|
| B–I (Pa-sepsis) | B–NI (niSIRS) | B–I:B–NI | |||
| Purine metabolism | |||||
| Uric acid | 0.893 ± 0.15 | − 0.277 ± 0.37 | 0.0042** | 0.93 | No |
| Pyrimidine metabolism | |||||
| 3-Ureidopropionate – RPI | 1.090 ± 0.17 | − 0.367 ± 0.65 | ns | 1 | Follow-upb |
| 3-Ureidopropionate – PI | 3969 ± 550.8 | 1809 ± 618.4 | 0.0314* | 1 | Yes |
| Thymidine | 1.330 ± 0.225 | − 0.687 ± 0.27 | 0.0074** | 1 | Yes |
| Thymine | 1.350 ± 0.21 | − 0.857 ± 0.525 | 0.0040** | 1 | Yes |
| Uracil | 1.250 ± 0.04 | − 0.780 ± 0.08 | < 0.0001**** | 1 | Yes |
| Uridine | 1.327 ± 0.20 | − 0.430 ± 0.345 | 0.0288* | 1 | Yes |
| Fatty acid and lipid metabolism | |||||
| Cholesterol | 1.017 ± 0.04 | − 0.110 ± 0.25 | 0.0301* | 1 | Yes |
| Glycerol-3-galactoside | − 0.953 ± 0.19 | 0.393 ± 0.52 | 0.0258* | 0.96 | Yes |
| Nonadecanoic acid | − 0.830 ± 0.11 | 0.357 ± 0.15 | 0.0007*** | 1 | Yes |
| Amino acid and protein metabolism | |||||
| 5-Oxoproline | 0.880 ± 0.08 | − 0.160 ± 0.22 | 0.0049** | 1 | Yes |
| Creatinine | 1.250 ± 0.21 | 0.087 ± 0.11 | 0.0098** | 1 | Yes |
| Hippurate | − 1.333 ± 0.53 | − 0.037 ± 0.27 | 0.0377* | 1 | Yes |
| Indole-3-acetate | − 1.220 ± 0.43 | 0.023 ± 0.23 | 0.0256* | 1 | Yes |
| Indole-3-propionate | − 1.583 ± 0.75 | 0.287 ± 0.12 | 0.0235* | 1 | Yes |
| Leucine | − 0.283 ± 0.24 | 0.710 ± 0.11 | 0.0351* | 0.81 | No |
| Methionine | − 1.033 ± 0.18 | 0.730 ± 0.41 | 0.0044** | 1 | Yes |
| Taurine | 1.190 ± 0.18 | − 0.770 ± 0.77 | 0.291* | 1 | Yes |
| trans-4-Hydroxyproline | 0.967 ± 0.06 | − 0.410 ± 0.16 | < 0.0001**** | 1 | Yes |
| Tyrosine | − 0.863 ± 0.28 | − 0.030 ± 0.29 | 0.0448* | 0.96 | Yes |
| TCA cycle | |||||
| Malate | 1.127 ± 0.27 | − 0.593 ± 0.07 | 0.0016** | 1 | Yes |
| Succinate | 1.280 ± 0.31 | − 0.433 ± 0.14 | 0.0015** | 1 | Yes |
| Glycolysis and gluconeogenesis | |||||
| 3,6-Anhydro-D-galactose | − 0.990 ± 0.23 | 0.340 ± 0.07 | 0.0005*** | 1 | Noc |
| 3-Phosphoglycerate | 1.767 ± 0.25 | − 0.267 ± 0.53 | 0.0055** | 1 | Yes |
| Fructose | − 0.807 ± 0.45 | 0.297 ± 0.26 | 0.0422* | 0.96 | Yes |
| Fructose-6-phosphate | 1.640 ± 0.45 | − 0.240 ± 0.30 | 0.0012** | 1 | Yes |
| Gluconate | 0.510 ± 0.36 | − 0.743 ± 0.49 | 0.0488* | 0.78 | Yes |
| Glucose | − 1.103 0.13 | 0.103 ± 0.21 | 0.0015** | 1 | Yes |
| Glucose-6-phosphate | 2.270 ± 0.23 | − 0.397 0.26 | < 0.0001**** | 1 | Yes |
| Lactate | 0.593 ± 0.16 | − 0.653 ± 0.37 | 0.0101* | 0.85 | No |
| Mannitol | − 0.497 ± 0.14 | 0.237 ± 0.13 | 0.0331* | 0.89 | No |
| Mannose | 0.850 ± 0.06 | − 0.273 ± 0.11 | 0.0023* | 1 | Yes |
| Phosphoenolpyruvate | 1.000 ± 0.11 | 0.070 ± 0.33 | 0.0219* | 0.96 | Yes |
| Vitamins and derivatives | |||||
| Oxalate | 0.553 ± 0.25 | − 0.113 ± 0.07 | 0.0474* | 0.85 | No |
| Xenobiotics | |||||
| 4-Methylbenzenesulfonamide | 0.813 ± 0.38 | − 0.407 ± 0.22 | 0.0169* | 1 | Noc |
| Conduritol-β-epoxide | − 0.573 ± 0.46 | 0.553 ± 0.17 | 0.0037** | 0.89 | Noc |
| Raffinose | − 0.880 ± 0.07 | 0.990 ± 0.66 | 0.0334* | 0.89 | No |
AUC area under the curve; RPI relative peak intensity; PI peak intensity; ns no significance; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001
aFor AUC, the cut-off for diagnostic discrimination was set at ≥ 0.96
b3-Ureidopropionate was selected in the first and second rounds of analyses and failed the third; as the AUC was 1.0, evaluation of the peak intensity values was done
cMetabolite has not been reported in humans; information obtained from the Human Metabolome Database (https://www.hmdb.ca/; accessed 12 Feb 2020) (Wishart et al. 2007)