Circulating inflammatory mediators in patients with fever: Predicting bloodstream infection

The systemic host response to microbial infection involves clinical signs a nd symptoms of infection, including fever and elevated white blood cell (WB C) counts. In addition, inflammatory mediators are released, including acti vated complement product C3a, interleukin 6 (IL-6), and the acute-phase rea ctant secretory phospholipase A(2) (sPLA(2)). To compare the value of the l atter with the former in predicting (the degree of) microbial infection at the bedside, we determined clinical variables and took blood samples daily for 3 consecutive days in 300 patients with a new fever (>38.0 degreesC rec tally or >38.3 degreesC axillary). Microbiological culture results for 7 da ys after inclusion were collected. Patients were divided into clinical and microbial categories: those without and with a clinical focus of infection and those with negative cultures, with positive local cultures or specific stains for fungal (n = 13) or tuberculous infections (n = 1), and with posi tive blood cultures, including one patient with malaria parasitemia. The ar ea under the curve (AUC) of the receiver operating characteristic (ROC) for prediction of positive cultures was 0.60 (P < 0.005) for peak temperature and 0.59 (P < 0.01) for peak WBC count, 0.60 (P < 0.005) for peak C3a, 0.63 (P < 0.001) for peak IL-6, and 0.61 (P < 0.001) for peak sPLA(2). The AUC under the ROC curve for prediction of positive blood cultures was 0.68 (P < 0.001) for peak temperature and 0.56 for peak WBC count (P < 0.05). The AU C for peak C3a was 0.69, that for peak IL-6 was 0.70, and that for sPLA(2) was 0.67 (for all, P < 0.001). The degree of microbial invasion is thus a m ajor determinant of the clinical and inflammatory host response in patients with fever. Moreover, circulating inflammatory mediators such as C3a and I L-6 may help to predict positive blood cultures, together with clinical sig ns and symptoms of the host response to microbial infection, even before cu lture results are available. This may help in the designing of entry criter ia for therapeutic intervention studies.