PCT

Let’s talk about procalcitonins (PCT)! I send this ALL the time in the ICU whenever admit a hypotensive patient, especially accompanied by suspicions for sepsis, CAP/aspiration pneumonitis, or COVID-19. If it’s high, then I think infection and it justifies my IV antibiotics order. But there’s always the evidence-based part of it that’s always crying for my attention. From what I hear, it’s good for trending antibiotic course but not the initial part. Let’s dive deeper into this, shall we?

What is PCT? It’s a biomarker and a natural pre-cursor to the calcitonin hormone. It’s produced in thyroid C cells and a lot are made with elevated calcium, gastrin, glucocorticoid, glucagon, and beta-adrenergic stimulation. But then healthy people usually convert all the PCT into calcitonin, which is why a normal PCT level is low in circulation. That’s the first way PCT is made. The second way (for our purposes) is made during inflammation when cytokines like IL-1, IL-6, TNF-a are released; like during SIRS and sepsis. PCT will usually rise 2–4 hours after the stimulation of the inflammatory response and peak after 24–48 hours.

Some research in observing PCT levels and PCT mRNA concentrations and thus forth have pretty much showed that PCT is good at differentiating between bacterial and viral infections, especially in pneumonias. After my lit review, it also seems that PCT is more sensitive and specific to diagnosing bacterial infections over other biomarker labs like CRP, ESR, and WBC. PCT is also good for diagnosing lower respiratory tract infections.

All this being said, if I suspect sepsis based on my SCC guidelines and have an initial elevated PCT, I will start my empiric antibiotics. I will have to do this especially with my SHK transplant patients. Even with initial PCT guidelines, a meta-analysis published on NEJM showed that there was no difference in ER prescriptions of antimicrobials using PCT and not using PCT. It’s hard to change what you’re used to as seen in this study. Now, how do I taper off my antibiotics using PCT?

One RCT conducted in multiple French ICUs from 2007–2008 called the PRORATA trial aimed to answer that. In short, they concluded that patients in the PCT arm had more antibiotic free days than the control group and mortality did not increase. For the PCT protocol they used:

• < 0.25 µg/l = stopping antibiotics strongly encouraged
• ≥ 0.25 and < 0.5 µg/l or ≥ 80% decrease from peak = stopping antibiotics encouraged
• ≥ 0.5 µg/l and < 80% decrease from peak = continuing antibiotics encouraged
• ≥ 0.5 µg/l and increase from peak = changing antibiotics strongly encouraged

But apparently, there has been much criticism for this trial. A lot of physicians involved with the PCT arm did not adhere to the guidelines, only 10% of the participants were SICU patients, and they used a 10% margin of non-inferiority threshold for mortality (which is a pretty wide margin). So all in all, it’s tough to use this study to justify what we should do. There is a RCT called SAPS (Stop antibiotics on guidance of Procal study) that I think is also recent in the Netherlands. They used a margin of non-inferiority was 8%. I can’t find the results so maybe analysis is still on-going?

What will I do with this info?

It seems like nothing. Again, making me a “smarter” person but not necessarily a better clinician. Antimicrobial stewardship is so important but we really dislike them because we really like our antibiotics and our gut feelings. Our gut feelings are always saying, patient has a fever and still on a little bitty levo, but negative PCT, so let’s continue our abx. More studies and trials need to be conducted and PCT-abx guidelines need to be adhered to in them to display competent data. For now, I will continue to send more initial PCT on admission and maybe trend them 48–72h while on abx. However, I will start observing the downtrend percentages and see if they are clinically improving. This will all be anecdotal until the professional people conduct their studies.

Dk

Things I read:

Huang D., et al. Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infections. N Engl J Med 2018; 379:236–249
DOI: 10.1056/NEJMoa1802670

Rhee C. Using Procalcitonin to Guide Antibiotic Therapy. Open Forum Infect Dis. 2016;4(1):ofw249. Published 2016 Dec 7. doi:10.1093/ofid/ofw249

Schroeder, S., Hochreiter, M., Koehler, T. et al. Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in surgical intensive care patients with severe sepsis: results of a prospective randomized study. Langenbecks Arch Surg 394, 221–226 (2009). https://doi.org/10.1007/s00423-008-0432-1

Vijayan, A.L., Vanimaya, Ravindran, S. et al. Procalcitonin: a promising diagnostic marker for sepsis and antibiotic therapy. j intensive care 5, 51 (2017). https://doi.org/10.1186/s40560-017-0246-8