Procalcitonin Takes Aim at Sepsis With Mixed Success

Season Osborne

February 27, 2020

The early diagnosis of sepsis is necessary to help patients and prevent the unnecessary use of antimicrobial agents. This serious condition, resulting from harmful micro-organisms in the blood or other tissues, and the body's response to their presence can lead to the organ malfunction, shock, and death.

Procalcitonin plays a critical role in the diagnosis of sepsis because it is virtually undetectable in the blood of healthy people, but shows up in the presence of a bacterial infection.

"Bacterial infections lead to an increase in the production of procalcitonin, whereas viral infections lead to a downregulation in production," so we can use this marker to identify whether "an infection is more likely to be bacterial or viral," said Ryan Maves, MD, infectious diseases fellowship program director and a staff intensivist at the Naval Medical Center in San Diego.

The use of procalcitonin as a tool to distinguish between viral and bacterial infections, as a marker of how severe the sepsis is and as a cue to determine when antibiotics can be safely discontinued was discussed during a debate at the Society of Critical Care Medicine 2020 Critical Care Congress in Orlando.

Both Maves and Ricard Ferrer, MD, head of the Intensive Care Department at Vall d'Hebron University Hospital in Barcelona, Spain, agree that the level of procalcitonin in the blood helps determine whether to administer antibiotics.

"Procalcitonin can help to diagnose sepsis, especially in cases where there is uncertainty," said Ferrer. And the level can be used to determine the severity of the patient's condition. The higher the procalcitonin level, the greater the mortality rate, he explained.

But Maves argued that serum procalcitonin is not the best marker of how sick a patient is.

There are a number of other tests that can be used to predict the severity of a critical illness, such as the Sequential Organ Failure Assessment (SOFA), he told Medscape Medical News.

And "if I have someone with a temperature of 39°C, a blood pressure of 70 over 30, and a white blood cell count of 30,000, I already know they are sick. An elevated procalcitonin does not confirm my finding," he added.

The bigger issue is in judging when to stop antibiotics, Maves said.

Antimicrobial Stewardship

There are standardized durations for antibiotic and antimicrobial therapy for the different types of bacterial infection, Maves pointed out, but they are "one size fits all."

With the push to reduce antimicrobial resistance, a good case can be made to tailor antibiotic use to blood test results. An increase in procalcitonin levels can be a signal to initiate antibiotics and a decrease can indicate that the patient is improving and antibiotics can be stopped.

"The algorithm for antimicrobial stewardship using procalcitonin, I think, is the most important aspect," said Ferrer. The strategy involves the periodic monitoring of procalcitonin levels in patients being treated with antibiotics, rather than using a fixed duration for that course of therapy.

"Studies have shown that this strategy is safe, it can reduce the use of antibiotics and cut cost, and some studies have shown that it can lead to a reduction in mortality," he reported.

But "if we are going to look at antimicrobial stewardship," said Maves, "I would argue that our first emphasis needs to be getting people to adopt short-course regimens for antibiotics, validated by clinical trials, before we use a blood test to replace our clinical judgment."

There are confounders that can also raise procalcitonin levels, he pointed out. For instance, patients with chronic and or acute kidney injury — a common problem in the ICU — have elevated levels of procalcitonin because they don't excrete it properly.

And a patient with viral pneumonia can have a secondary bacterial infection. It is not clear how this affects the production of procalcitonin, he added.

Perhaps a combination of biomarkers will ultimately become a functional clinical application. A mix of emerging new biomarkers and procalcitonin-guided antibiotic stewardship might offer a safer, more affordable strategy for the diagnosis of sepsis and its prognosis.

Society of Critical Care Medicine (SCCM) 2020 Critical Care Congress. Presented February 18, 2020.

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