C-reactive protein and procalcitonin: prognostic and therapy guidance tools in intra-abdominal sepsis

Abstract

Among the recent advances in the management of intra-abdominal sepsis are the use of two biomarkers of inflammation, Creactive protein (CRP) and procalcitonin (PCT). Both biomarkers were investigated for their potential use for diagnosis, prognosis and therapy guidance 1-3. Any use of these two biomarkers must be based on a detailed understanding of their biology. The goals of the presentation are to review: (i) the biology of CRP and PCT; (ii) the diagnosis and prognosis performances of the two biomarkers in bacterial (including intra-abdominal) sepsis; (iii) the potential use of these biomarkers to guide therapy. C-reactive protein (CRP), named for its capacity to precipitate the somatic C-polysaccharide of Streptococcus pneumoniae, was discovered in 1930 (see for a review 4 and is a major component of the acute phase reaction (APR). In healthy young adults, the median concentration of CRP is 0.8 mg/l, the 90th centile is 3.0 mg/l, and the 99th centile is 10 mg/l 5 . Within 24 h after onset of inflammation, levels can increase as much as 1000-fold 5 . Measurements of plasma CRP concentrations are routinely used in clinical practice to diagnose acute inflammation, follow up its response to therapy, diagnose infection in immuno-compromised host when other clinical signs are not sensitive. Procalcitonin (PCT) is a peptide barely detectable in healthy patients but its concentration can be increased several thousand fold in cases of inflammation secondary to bacterial and fungal infection but also to non-infectious causes 6-9. As a biomarker of inflammation/ bacterial and fungal infection, as comparable to other biomarkers such as C-reactive protein (CRP) 5 , PCT is particular in that the significance in terms of outcome (beneificial, deleterious or neutral) of its increased concentrations is not understood 6;7. For instance, high PCT values in neonates or patients with medullary carcinoma of the thyroid gland do not affect patient outcome 6 ; on the contrary, high PCT values are statistically associated with patient outcome in variety of clinical contexts characterized or not by bacterial or fungal infection 10;11. The diagnostic and prognostic performances of PCT and CRP are probably not good enough to be used isolated from other clinical and laboratory information 12 . Nevertheless, accumulation of clinical experience and published reports is consistent with a very high negative predictive value of low PCT values 12. Low (< 0.25 µg/l) PCT values are consistent with absence of severe bacterial infection at least for some clinical contexts12. In addition, several clinical trials that still require confirmation with larger cohorts of patients, suggest that PCT could be used to guide the duration of antibiotic therapy is critically ill patients or in patients admitted to the emergency department 12-18. In summary, although it is too early to assert that information provided by serial PCT measurements could change clinical reasoning on initiation and duration of antibiotic treatment in critically ill patients, recent results suggest that this may be the case.