Procalcitonin in Sepsis and Antibiotic Therapy

Introduction
Diseases with high morbidity and mortality rates need timely diagnosis and treatment in their early stage to avoid the worst scenarios. In infections such as Sepsis, the severity of infection is directly proportional to the increase in mortality. Late diagnosis and no treatment can lead the Sepsis to affect multiple organs, resulting in fatal outcomes. This implies that there has to be a definitive diagnostic marker to detect Sepsis at the earliest. This is where Procalcitonin comes into the picture. Procalcitonin is helpful in the early detection of Sepsis and monitors the antimicrobial treatment regimen. Studies also show that the use of procalcitonin can significantly reduce the unnecessary administration of antimicrobial therapy.
This article briefly explains the role of procalcitonin in sepsis diagnosis and antimicrobial therapy.

Relation between Sepsis and Procalcitonin

Sepsis is an immune response to the prevailing microbes such as viruses, fungi, parasites, and bacteria that attack the body. Sepsis can be termed a systemic inflammatory response syndrome that affects all body organs. Sepsis caused by bacteria is common and found to be more invasive. The microbes get into the bloodstream and lead to local proliferation resulting in the release of various virulent substances. These substances could provoke the endogenous mediators to get released into the blood from various immune sites: macrophages, neutrophils, monocytes, and plasma cell precursors. In this situation, the body attempts to neutralize the generated pathogenicity by activating mechanisms of the immune cell to exude inflammatory proteins, damaging tissues, and organs of the body. This leads to the exhibition of the sepsis-related inflammatory immune response.

Procalcitonin is a peptide precursor produced mainly by the C cells of the thyroid and some amount by the endocrine cells. It is characterized as ‘homokines’ due to its dual nature, i.e., hormonal origin and roles in the inflammatory response. The CALC-1 gene on chromosome number 11 is the site for procalcitonin synthesis. During infection, the production of procalcitonin is governed by alternative pathways instead of the normal pathway via thyroid cells.

Studies have found an increase in the expression of the CALC-1 gene during Sepsis. This relates to the rise in procalcitonin production. The inflammatory response of Sepsis triggers the alternative pathway of procalcitonin synthesis. So instead of generating calcitonin, this precursor of calcitonin diverts towards producing more procalcitonin.

In a nutshell, there is a proportional relationship between the levels of procalcitonin and the severity of Sepsis.

Role of procalcitonin in diagnosing Sepsis

Procalcitonin is found to be an emerging biomarker that ticks most of the squares for holding the position of diagnosing Sepsis and other diseases. It suffices to define an ideal diagnostic marker where accuracy, specificity, promptness, and reliability matter a lot.
Procalcitonin stands as a blood test that fulfills most of the requirements for diagnosing a bacterial infection better than other existing markers. It has been found that procalcitonin is a better diagnostic marker than CRP (C Reactive Protein) in bacterial infection. Accuracy in detection and the level of severity is better determined by procalcitonin, which on the other hand, is lacking by CRP. Tumour necrosis factors (TNF alpha), Interleukins (IL-6, IL-11), are the different blood tests used for diagnosing Sepsis. However, the reliability is comparatively less than that of procalcitonin.

An article published in the Journal of Infectious Disease and Epidemiology mentions that Procalcitonin is a better prognosis marker for Sepsis and is applicable for making the differential diagnosis (differentiating bacterial infection from other infections that features inflammatory responses).

In patients suffering from autoimmune diseases, it is hard to identify bacterial infections due to the similar clinical presentations in the underlying disease. Here, procalcitonin could be an excellent marker for diagnosing bacterial infection even in the presence of therapies involving corticosteroids (manufactured drugs that reduces inflammation) and immunosuppressive agents, which at times create difficulty in diagnosis.

Role of procalcitonin in antibiotic therapy

An article published in the American Journal of Health-System Pharmacy mentions that in the early 90s, France accomplished the first study suggesting the efficacy of procalcitonin in identifying bacterial infection. Since then, several studies have been done on the usefulness of procalcitonin in diagnosing bacterial infection and assisting in the course of its treatment.

The subsequently recorded levels of procalcitonin have been found to help medical practitioners decide on when to start or stop the therapy and enable them to determine if the doses are required to be altered or not. Thus, procalcitonin significantly reduces the probability of late treatment incidences, or the patient was offered an inappropriate treatment due to the poor diagnosis.

Antibiotic therapies are usually employed for treating bacterial infections, including Sepsis or septic shock. When choosing an antibiotic for Sepsis, several essential things should be kept in mind, including

• The antibiotic should be of the broad spectrum to cover both gram-negative and gram-positive organisms
• Should be effective against multi-resistant bacteria
• Should be highly susceptibility

However, if continued for the long term, antibiotic therapies will cure the sepsis infection, but they might negatively impact health. For example, a few clinical trials had shown that antibiotic exposure to patients with a bacterial infection could be significantly reduced when procalcitonin levels were constantly monitored. This, in a way, also prevents one from facing the side effects of antibiotic therapies.

Procalcitonin is found to have a short half-life of about 25-30 hours. The levels of procalcitonin rise rapidly in response to the inflammatory condition and reach their peak, showcasing the degree of intensity of the reaction. Similarly, its levels rapidly decline too when the inflammation is on the verge of settling down. This property of procalcitonin potentially helps determine to which stage the infection is. Also, it helps to suggest the initiation and the discontinuation point of antibiotic therapy.

Summarising

Procalcitonin has been found to contribute immensely in assisting the diagnosis and treatment of Sepsis. Several studies are making this claim stronger, and at the same time, a few ones suggest that there still exists a need for a strong assertion for it to be implemented completely. However, it could still be taken into practice to help the physicians empower the diagnosis and monitor the course of treatment only after correlating its results with other pathological findings.

References:

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