C-reactive protein, procalcitonin and interleukin-8 in the primary diagnosis of infections in cancer patients

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Abstract

The diagnostic utility of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-8 (IL-8) were studied in 66 cancer patients with suspected infection (39 with definite foci of infection, 17 with antibiotic responses without foci and 10 with neoplastic fever without infection) and 26 patients scheduled for chemotherapy. The infection group (n=56) had higher median CRP (91 versus 19 mg/l, P<0.001), PCT (0.28 versus 0.12 ng/ml, P<0.001) and IL-8 values (27.7 versus 16.9 pg/ml, P=0.032) than the non-infection group (n=36). In patients with suspected infection, only PCT was a good marker to discriminate bacteraemia with an area under the receiver operating characteristics curve of 0.92 (95% confidence interval (CI), 0.77–1.0), but even PCT was less well able to differentiate between non-bacteraemic infections and neoplastic fever (0.56; 95% CI, 0.35–0.77). In conclusion, PCT was a good indicator for bacteraemia, but none of the three markers were reliable indicators for minor infections in non-neutropenic cancer patients.

Introduction

Procalcitonin (PCT), a 116 amino acid propeptide of calcitonin, has been proposed as a new diagnostic marker of severe infections [1], such as neonatal infections 2, 3, septic shock 4, 5 and bacterial meningitis [6] as well as pyelonephritis amongst children [7]. In normal individuals, calcitonin and PCT are produced by C-cells of the thyroid gland, but the reason for increased PCT secretion in patients with severe infections is not known [1]. Enhanced production of calcitonin-like peptides or calcitonin-precursor peptides is also seen in patients with different malignancies [8] PCT has been shown to be a promising indicator for bacteraemia, even in neutropenic patients with haematological malignancies 9, 10, 11.

Interleukin-8 (IL-8) is an important chemotactic regulator of neutrophil function in vivo 12, 13. Its concentration increases during different infections, such as bacteraemia [14] and meningococcal disease [15]. High IL-8 concentrations have also been demonstrated in association with malignancies 16, 17. In neutropenic patients, enhanced IL-8 production has been demonstrated comparable with PCT in predicting bacteraemia [11].

C-reactive protein (CRP) is the most widely used marker of ongoing infection in clinical practice 18, 19. The use of CRP values to diagnose infection in cancer patients is often difficult, because the underlying malignancy also induces CRP production in hepatocytes 19, 20. Actually, the activation of an acute-phase response is regarded as prognostic in oncology 21, 22, 23.

The purpose of our prospective study was to assess whether PCT and IL-8 are more useful than CRP to identify infection in non-neutropenic cancer patients, which would help to avoid unnecessary antibiotic treatment as well as hospitalisation.

Section snippets

Study design for the identification of study groups

The study protocol was approved by the Ethics Review Committee of the Medical Faculty of the University of Oulu, Oulu, Finland. Between September 1996 and March 1998, 92 consecutive cancer patients with suspected infection and Karnofsky performance scores higher than 40 were enrolled in this prospective study at the Department of Oncology and Radiotherapy, Oulu University Hospital, Finland. When the oncologist in charge suspected infection, oral and written informed consent was obtained from

Results

26 of the 92 patients (28%) with suspected infection did not meet the abovementioned classification criteria. In these cases, simultaneous antibiotic and cancer treatments did not allow classification, and these 26 patients were therefore excluded from the study. From the remaining 66 cancer patients, 56 had the following infections: 8 had bacteraemia (3 had Staphylococcus aureus, and 1 each Escherichia coli, Pasteurella multocida, Clostridium bifermentans, another gram-negative anaerobic rod

Discussion

Our results show that the discriminatory power of PCT amongst cancer patients was best for bacteraemia with an AUC value of 0.92, whilst its ability to discriminate minor infections from neoplastic fever was less good with an AUC value of 0.56. In contrast, the AUCs of CRP and IL-8 were poor for both bacteraemia and other infections in this population with solid tumours, of whom most were non-neutropenic and non-bacteraemic. Thus, our study population differs from those previously reported,

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