Circulating Inflammatory Mediators in Patients with Fever: Predicting Bloodstream Infection

Abstract

The systemic host response to microbial infection involves clinical signs and symptoms of infection, including fever and elevated white blood cell (WBC) counts. In addition, inflammatory mediators are released, including activated complement product C3a, interleukin 6 (IL-6), and the acute-phase reactant secretory phospholipase A 2 (sPLA 2 ). To compare the value of the latter 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°C rectally or >38.3°C axillary). Microbiological culture results for 7 days 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 positive blood cultures, including one patient with malaria parasitemia. The area 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 AUC 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 major determinant of the clinical and inflammatory host response in patients with fever. Moreover, circulating inflammatory mediators such as C3a and IL-6 may help to predict positive blood cultures, together with clinical signs and symptoms of the host response to microbial infection, even before culture results are available. This may help in the designing of entry criteria for therapeutic intervention studies.

Diagnosis of infection in sepsis: An evidence-based review

“…These include chills, hypoalbuminemia, the development of renal failure, and a diagnosis of urinary tract infection (17,18); other criteria are new fever, hypothermia, leukocytosis and left shift of neutrophils, neutropenia, and signs of hemodynamic compromise (19). Peaking fever appears to be more sensitive than leukocytosis to predict bacteremia (20); however, fever and low-grade bacteremia can be continuous, such as in endocarditis.…”

Circulating Granzymes are associated with Bloodstream Infection and Death in Febrile Medical Patients

“…The patients included in this study participated in a protocol in which 300 consecutive patients with newly onset fever (body temperature >38 °C axillary or 38.3 °C rectally), admitted to the Department of Internal medicine in an University Hospital, were included, as described elsewhere [19] . For the present study plasma samples from 284 patients were available.…”

Mannan binding lectin in febrile adults: no correlation with microbial infection and complement activation

“…Some of the data collected in this cohort have been published previously. 9 We now report on the 177 patients in whom it was possible to determine MBL at inclusion into our study. The study was approved by the local committee on ethics.…”

“…9 Supplementary blood cultures were taken when clinically indicated. Local specimens for culture were collected by the attending physician, depending on the clinical situation; that is, when a focus of infection was suspected.…”

“…9 Results were expressed as nmol/litre. Normal values in healthy volunteers are less than or equal to 5 nmol/litre.…”