Benefits of Procalcitonin

Hello, everyone. I’m Dr. Kordo Saeed, and I would like to briefly talk about the benefits of procalcitonin as an antibiotic stewardship tool and how it’s a better marker in distinguishing bacterial from viral infections. For further information, please complete the rest of the course and consider checking the references provided throughout the course. Procalcitonin is a peptide. In healthy individuals it’s produced mainly by C cells of the thyroid gland and, to some extent, small cells of the lung. Soon after its release, procalcitonin is enzymatically converted to two components. One of them is calcitonin, which is mainly involved in calcium metabolism, and the second one is katacalcin, which to my knowledge, its function is not fully known.

This rapid enzymatic conversion is really important because it renders undetectable in healthy individuals, at least in those without bacterial infection. However, when there is bacterial infection, where there is release of toxins and cytokines - for example, Tumour Necrosis Factor alpha, almost every single tissue and organ in the body starts to produce procalcitonin, i.e., there would be more of it that would be released into the bloodstream which would be measurable, and this makes it a useful marker to signal infection. The reason why it’s more specific for bacterial infection is that interferons, which are released during viral infection, inhibit the production of procalcitonin.

Hence we don’t see much rise, or we see no rise in procalcitonin during viral infections compared to bacterial infection. With exception are those viral infections where they get complicated by secondary bacterial infection.

The role of procalcitonin in healthy individuals is not fully known. Some suggest it can act as a neurotransmitter or as a maintainer of the vascular tone. In bacterial infection, again, its function is not fully understood. However, studies in animals suggest by giving anti-procalcitonin antibodies to septic animals, either at the beginning of the sepsis process or at the premorbid stage, giving anti-procalcitonin antibodies can improve survival. Hence its role could be more a pro-inflammatory role during the sepsis process. Another interesting fact about procalcitonin is that it goes up much faster during bacterial infection compared to CRP.

As you can see on the graph, procalcitonin here represented by the orange line, during bacterial infection it starts to go up around four hours from the insult, and it peaks around 12 hours. And if there is adequate treatment with antibiotics or source control, it declines much faster compared to CRP, where it takes almost 36 to 48 hours to peak and its rate of decline is much slower. This is important because what it means in clinical practise, a rise in CRP represents an event happened almost 36 to 48 hours ago, while a rise in procalcitonin could represent an event happened six to 12 hours ago. So more of a representative of real life event, rather than the CRP.

We have demonstrated the dynamics of procalcitonin and CRP in this study, which included 50 patients prospectively enrolled for serial procalcitonin and CRP measurements after major abdominal surgery.

Bloods were taken upon day zero prior to the surgery and then on day one, three, and six postoperatively. Patients were then assigned to infected and non-infected groups. The infected group here is represented by the red line and the uninfected by the green line. The grey bar is where we diagnose the infection based on clinical and/or microbiological and/or radiological parameters. As you can see, procalcitonin went up almost 24 hours before the grey line. The CRP, although it went up, was almost 24 hours after that grey line.

This is very important, as the sooner we diagnose - or we have a signal to suggest bacterial infection, the sooner we implement measures - for example, antibiotic treatment or look for a source and perform source control - the better would be the outcome for the patient. Additionally, when patients were treated adequately, the procalcitonin declined to almost normal levels by day six, while CRP is still in mid-hundreds. This decline is also important because it can reassure clinicians that their treatment is working. And it can aid stopping antibiotics sooner, which is a really important element of antimicrobial stewardship programmes.

I would like to emphasise here that although it’s a better marker for bacterial infection, at least from the antimicrobial stewardship point of view, procalcitonin should only be used within clinical context, and using correct cutoffs provided here for correct patient categories based on previous studies and publications.

Clinical judgement is always superior, as no diagnostic test is 100% sensitive or specific. In summary, I hope I have highlighted why procalcitonin is more specific for bacterial infections, the dynamics of procalcitonin and CRP, and how procalcitonin goes up much faster in bacterial infection and declines faster if there is adequate treatment and source control. We should always use it within the right clinical context, allowing clinicians to make their judgement based on the full picture and not any single biomarker in isolation. Thank you.