Expert: Sutirtha Chakraborty, MBBS, MD, FACB

Why should procalcitonin testing be a part of the sepsis management protocol?

Globally, sepsis and its complications are a major cause of acute illness and death. The American College of Chest Physicians and Society of Critical Care Medicine defined sepsis as systemic inflammatory response caused by infection. However, the major challenge remains, how can we prove there is an infection? Culture best identifies it, but only in about 30% of patients with sepsis. False positivity of cultures further complicates the situation. Clinical signs of sepsis—including fever, tachycardia, and leucocytosis—are non-specific and overlap with signs of systemic inflammatory response syndromes (SIRS) of non-infectious origin, making detection of sepsis a clinical challenge. As a result, delay in diagnosis and treatment of sepsis is responsible for increased mortality.

In order to prove the presence of bacterial infection, serum biomarkers like procalcitonin (PCT) are considered useful. Biochemically, PCT is the prohormone of the hormone calcitonin, released into the circulation in response to bacterial infection. PCT is the best-studied sepsis biomarker for clinical use. Among all sepsis markers, only PCT has achieved universal use throughout developed countries in the last decade. 

One major advantage of PCT compared with other biomarkers is its early and rapid increase in response to bacterial infections and sepsis. High PCT concentrations are commonly found in bacterial infection, in contrast to much lower levels in viral infection.However, even though PCT is vir­tually undetectable (less than 0.1 ng/mL) in healthy individuals, elevated serum PCT concentrations are not always specific for sepsis. Many studies have linked elevated PCT to SIRS, localized bacterial infection, autoimmune disease, burns, severe trauma, surgery, pancreatitis, as well as viral, parasitic, and fungal infections.

Despite these challenges, PCT has some other obvious clinical advantages: improved accuracy of early clinical sepsis diagnosis, utility for assessing effectiveness of sepsis treatment, and a role in antibiotic stewardship. For respiratory tract infection in intensive care unit patients who have sepsis and post-operative infections, randomized-controlled studies have shown the efficacy of using PCT algorithms to guide antibiotic decisions. PCT-guided antibiotic therapy leads to significant reduction in the length of antibiotic therapy. However, serial PCT measurements are needed in order to judiciously use PCT in assessing therapeutic effectiveness and antibiotic stewardship. Surviving Sepsis Campaign: International Guidelines (2012) suggests that PCT measurements can be used for sepsis diagnosis and to discontinue antibiotic therapy in patients who initially seem septic, but have no subsequent evidence of infection.

PCT has a very high negative-predictive­ value as a marker of bacterial infection, making it useful to rule out sepsis in emergency department and critical care settings. Nevertheless, falsely low PCT levels can be seen during the early course or localized state of an infection. As such, one critical area for further research is highly sensitive PCT assays that allow monitoring of subtle changes of PCT at very low concentrations. This will increase the sensitivity of the test and thus the safety of patients. PCT has the ability to be the troponin of bacterial sepsis provided such highly sensitive assays can be developed.

Like any biomarker, PCT is not perfect and has some significant limitations. It is an expensive test to run, significantly more than C-reactive protein, blood counts, and other assays. It is not, therefore, the single definitive test for sepsis diagnosis, but rather must be interpreted in context of medical history, physical examination, microbiological assessment, and other relevant laboratory parameters. Nevertheless, PCT use has the evidence base of several high quality large clinical trials making it one of the strongest contenders of the sepsis biomarker arena.

Sutirtha Chakraborty, MBBS, MD, FACB, is the chief consultant in the Department of Clinical Biochemistry at Peerless Hospital & B K Roy Research Center, Kolkata, India. +Email: sutirtha@peerlesshospital.com