Procalcitonin: a valuable markerfor assessment of the success of antimicrobial therapy for severe sepsis An analysis using routine clinical data

Abstract

Introduction and Objectives       

Procalcitonin (PCT), a precursor of the hormone calcitonin, is produced byC cells inthe thyroid. PCT is consistently produced duringsevere bacterial infections,causing its levels to increase [1,2].However,increased PCT levels are alsocharacteristic of other disease states, such as calcitonin-producing tumors, medullary C-cell carcinoma of the thyroid, acute respiratory distress syndrome,and invasive fungal infections. In particular,extensive clinical evidence indicates that PCT is a biomarker for both follow-up and evaluation ofthe effectiveness of antibiotic therapyfor severe respiratory infections and sepsis; in all relevant guidelines, the use of PCT in this contextis categorized asevidence class 2B or 2C [3,4]. For example, PCT levels differentiatemore effectivelybetween sepsis and systemic inflammatory response syndrome (SIRS)than those ofIL-6, IL-8, or CRP[5,6]. A meta-analysis of several clinical studiesofvarious infections demonstrated that PCT-guided antibiotic therapyreduced both therapy duration and the length of stay in intensive care [7].Based on this broad evidence, another meta-analysis focused on sepsiswas conducted, the results of whichindicatedthat antibiotic therapy can be curtailed by a mean of four days, and length of ICU stay reduced by a meanof 1.8 days. Based on existing algorithms,we determinedasequence of PCT measurementsappropriateto guide the use ofantibiotic therapy. In addition,rules for when therapy should commence and end, and cut off values to evaluate successful treatment have been established. Implementation of this system may introduce savings for the German diagnosis-related group(G-DRG) system [8].

A fall in PCT levelsby 80% compared withthe highest value, or to 0.25 ng/ml, indicatesuccessful antibiotic therapy. Hochreiter and Schröder showed that,in the case of adequate antibiotic therapy,PCT levels decreasesignificantly after 4 days [9]. In addition, Charles et al. demonstrated that a lack of PCT reduction on day 3,compared withday 2, of antibiotic therapyis a resilient indicator of inadequate treatment (OR = 10.29) [10].

Once guidelines and algorithms have been established for some time, the question of how well they are implemented in practice in theclinic arises.