TREM-1 is a recently discovered member of the immunoglobulin superfamily of receptors that is specifically expressed on the surfaces of neutrophils and monocytes. sTREM-1 is a soluble form of TREM-1 and is released into bodily fluids when TREM-1 is upregulated. Many studies have indicated that sTREM-1 could be a valuable diagnostic biomarker for various infectious diseases [21
]. Dynamic changes in sTREM-1 levels could predict survival and mortality of patients at the early stage of sepsis [28
]. PCT expression is related to the severity of bacterial infection; hence, it is one of the biomarkers for infection [31
]. PCT measurements along with other clinical tests for infection might be valuable for determining the prognosis of patients [33
]. CRP is a biomarker involved in variety of inflammatory diseases. Although the majority of hospitals can widely implement CRP analysis in sepsis diagnosis and prognosis [35
], whether CRP is a good biomarker for early diagnosis of sepsis or bacteremia is still controversial [37
]. Our study found that sTREM-1, PCT, and CRP levels indicate infection, while sTREM-1 and PCT levels predict prognosis. However, none of these parameters brings to light the cause of new fever. Moreover, sTREM-1 is the best indicator for diagnosis of sepsis and assessment of prognosis of blood culture-positive bacteremia.
Rivera-Chavaz et al.
] performed a study involving 93 patients in the ICU with SIRS symptoms and suspected infection. The patients were classified as having SIRS (no infection; n
37) or sepsis (n
56) according to the diagnosis of the physician in charge and clinical evidence. Patients with sepsis had significantly higher sTREM-1 levels than did those with SIRS. At a cut-off of 30
pg/mL, sTREM-1 correctly identified patients suffering from infection with 96% sensitivity and 91% specificity. Porfyridis et al
] enrolled 68 patients with acute respiratory illness. A total of 34 patients were diagnosed with community-acquired bacterial pneumonia and 34 with nonbacterial pulmonary disease. sTREM-1 levels were significantly higher in the pneumonia group than in the nonbacterial pulmonary disease group, and this analysis was more sensitive and specific than analysis with CRP levels. Yong J et al.
] performed a meta-analysis of 13 clinical studies that fulfilled the inclusion criteria (980 patients; 557 patients with bacterial and 423 with nonbacterial infections). They found that sTREM-1 level for the diagnosis of infection in the AUC of the summary ROC was 0.86, with a sensitivity of 0.82 and specificity of 0.86. This finding confirmed that sTREM-1 is a reliable biomarker for bacterial infection. However, other studies argue that sTREM-1 is of no value for infection diagnosis [42
]. Some experts have suggested that CRP and PCT levels are more sensitive than sTREM-1 as biomarkers for the diagnosis of bacterial infection [45
]. Our study, on the other hand, found that on the day of ICU admission, the sepsis group had higher sTREM-1, PCT, and CRP levels and APACHE II scores than did the SIRS group. The indicators above, to different degrees, have values in sepsis identification or diagnosis, of which sTREM-1 proves most efficient. Data obtained through our study are quite similar to those previously reported.
There have been numerous studies on PCT. Stefan et al.
] enrolled 295 patients whose blood culture samples were collected at the emergency department. Based on the blood culture results, the patients were categorized into blood culture-positive, blood culture-negative, and blood culture-contaminated groups. The results indicated that PCT is the most valuable biomarker for the diagnosis of sepsis and bacteremia for patients in the emergency department. Kim et al.
] and Lai et al
] also arrived at the same conclusion: that PCT levels are the most meaningful parameter for bacteremia diagnosis and for patients with bacteremia and a high fever in the emergency department. On the contrary, CRP levels have no value for diagnosis of patients with bacteremia and a high fever in the emergency department. However, Blijlevens et al.
] questioned the value of PCT levels in sepsis diagnosis. Ruiz-Gonzalez et al.
] recently suggested that sTREM-1 levels are valuable for diagnosing bacteremia with community-acquired pneumonia. Because fewer studies have shown the value of sTREM-1 in the diagnosis of bacteremia, we divided ICU patients with fever into blood culture-positive bacteremia and blood culture-negative groups based on their blood culture results. We found that sTREM-1 and PCT levels in the two groups were very comparable. Interestingly, CRP levels were significantly higher in the blood culture-negative group than in the bacteremia group (P
0.033). We speculate that this occurred because of the rise in CRP reactivity rather than because of the bacteremia itself. Our study implies that sTREM-1, CRP, and PCT levels may possess no clinical value in determining whether a given septic patient is complicated with bacteremia on the grounds of a new fever.
Gibot et al
] studied sTREM-1 levels in 63 patients with severe sepsis and found that decreased sTREM-1 plasma levels were positively correlated with a better prognosis. Thus, sTREM-1 is an excellent biomarker for the prognosis of sepsis. Furthermore, our previous studies and Gibot S et al
] found that compared with PCT and CRP levels, dynamic changes in sTREM-1 levels better predict the prognosis of sepsis. However, no studies have reported whether sTREM-1, PCT, or CRP levels are good parameters for the prognosis of bacteremia. We herein showed that sTREM-1 and PCT levels were useful for the prognosis of blood culture-positive bacteremia. For example, within the bacteremia group, sTREM-1 and PCT levels were significantly higher in nonsurvivors than in survivors. However, we failed to find any prognostic value of sTREM-1 or PCT for blood culture-negative sepsis. Moreover, according to the ROC curves of sTREM-1 and PCT levels, sTREM-1 is a more ideal predictor for the prognosis of blood culture-positive bacteremia. Thus, physicians are expected to pay close attention to patients with high levels of sTREM-1.
Our study was, however, limited by the following factors. (1) The study involved a small sample size; only 33 patients with a positive blood culture were enrolled. (2) Only those who developed a new fever (>38.3°C) in the ICU were enrolled. Therefore, we cannot exclude the possibility that patients who did not have a high fever also had bacteremia; unfortunately, however, no such patients were involved in our analyses. (3) The incidence of opportunistic infections is higher in the ICU, and many pathogens circulate in the wards. Consequently, the possibility of false-positive blood cultures could not be excluded. Furthermore, the patients received regular antibiotic treatments, and side effects of such a long-term treatment should not have been ignored. (4) It is well known that more than two-thirds of patients with severe bacterial sepsis have negative blood cultures [52
], but this fact (blood culture negative bacteremia) was not properly addressed in the study.