In the present study we attempted to evaluate whether MR-proADM and PCT could play a relevant role in decision making for the disposition of the febrile patients in the ED. We tried to understand the real diagnostic and prognostic weight of the two biomarkers for the emergency physician in taking care of a critical febrile patient.
First we tested the diagnostic relevance of infection for the two biomarkers, comparing the values detected in patients with those of healthy control individuals. According to literature [6
], our data confirmed higher values of both biomarkers in febrile patients compared to healthy controls (Table b).
PCT added diagnostic value to the currently routine variables (CRP, WBC count) for the identification of infection in patients with fever. A negative value of PCT should be of relevance in ruling out the presence of infections, which is helpful when choosing the admitting ward and/or antibiotic treatment [14
Concerning the prognostic role of MR-proADM and PCT, we evaluated the ability of MR-proADM and PCT in predicting the subsequent hospitalization of patients who arrived at the ED complaining of fever. Our data demonstrated a better predictive value, even slightly, for PCT than MR-proADM (AUC of 0.763 and a p =0, 0001 versus an AUC of 0.694 and a p =0, 0002, respectively). The hospitalization’s predictive value rose if the two biomarkers were used together (AUC of 0.79 and p =0, 0001 – Figure ).
Focusing on data emerging from this study, we can highlight that MR-pro ADM and PCT levels are elevated in critically ill febrile patients, and that they seem to have a prognostic value similar to the APACHE II score, providing an additional margin of safety. Thus, we evaluated the potential correlation between the two molecules and the APACHE II score, to determine the possible additional value of PCT and MR-proADM in predicting the outcome of the febrile patient attending the ED [14
]. The APACHE II score has been expressed in predicted mortality percentage.
The Apache II score was grouped into quartiles and compared with levels of MR-proADM and PCT. MR-proADM and PCT levels were significantly stepwise increased in accordance with the Apache II quartiles with a p
respectively (Figure a, b), proving that a higher value of MR-proADM and of PCT corresponds to a higher APACHE II score.
A positive correlation between the APACHE II score and both biomarkers was found in all patients, considered in their globality, with a p <0.0001 for MR-proADM and a p =0.003 for PCT.
Although a direct correlation between MR-proADM and PCT and mortality cannot be shown, the correlation between the two biomarkers and the APACHE II score seems to assert their prognostic role in the febrile patient attending the ED, suggesting that MR-proADM may predict mortality in a larger number of clinical conditions, compared to PCT. Moreover, we found a stepwise increase of MR-proADM levels with PCT values (P<0.0001
- Figure ).
To date, PCT is described as a marker of bacterial infection, but it has also been proposed and identified as a mortality predictor in patients with community-acquired pneumonia, in critically ill patients with sepsis, and in those with ventilator associated pneumonia [19
]. In order to support this, several studies have demonstrated the diagnostic role of PCT in detecting bacterial infection and sepsis [14
], and further papers have investigated its prognostic value [27
]. In this perspective, our data suggest that the positive correlation between PCT and the APACHE II score in febrile patients who arrive in the ED correspond to the prognostic value of the APACHE II score [34
]. Moreover our data show that higher levels of PCT are related to more-severe infections and worse prognosis, as evidenced by the following division of the patients into 5 groups based on the clinical diagnosis made in the ED: respiratory infections group, urinary infections group, sepsis and septic shock group, unspecified fever group, and “other” group (Table ). In patients so grouped, a positive correlation between the APACHE II score and MR-proADM was found in the respiratory infections group (r
0.0002), in the urinary infections group (r
0.001) and in the sepsis and septic shock group (r
0.02). For PCT, the positive correlation with the APACHE II score was found only in the sepsis and septic shock group (r
We can also suggest that the use of these biomarkers in the febrile patient could not only improve diagnostic and prognostic accuracy, but could also promote a rational use of antibiotics, in terms of reduction of antibiotic overconsumption and adverse events as shown in recent studies that point to the effectiveness of PCT in safely reducing the number of unnecessary antibiotic prescriptions [2