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Controversies and limitations of PCT

Dr Kordo Saeed discusses the limitations and barriers of PCT in this video.
Hello, everyone. I’m Dr. Kordo Saeed, and I would like to briefly talk about limitations and controversies related to procalcitonin and its ability to assist antimicrobial stewardship. First of all, barriers in using procalcitonin. There are numerous barriers as to why procalcitonin hasn’t taken off in some places as an antimicrobial stewardship tool. The first barrier is cost per test. It’s generally more expensive than CRP, at least in the United Kingdom. But in my experience, if you could use it based on algorithms and local guidance and not as a box ticking exercise, then it will likely result not only in antibiotic saving, but in cost savings, too. However, I do think more robust cost-effectiveness analysis and studies are required.
Availability of labs or availability of procalcitonin in your lab could be an issue. There are point of care tests which have been marketed, but they have their own advantages and disadvantages. Lack of experience on how to use procalcitonin and incorporate it in an antimicrobial stewardship tool could be a barrier. There are now international consensus guidance and algorithms that could be used as a guide, but we need to take local needs and requirements into account whenever we try to introduce a new test into our clinical practise. Like other medical tests, procalcitonin has its own limitations. First of all, it doesn’t identify pathogens, i.e. it doesn’t differentiate staph aureus from pseudomonas infection.
Nonspecific rise or false positives can happen in certain conditions, like poly trauma, severe burns, patients who are on immunomodulators. Also, there is physiological increase of procalcitonin during pregnancy and neonatal periods. Certain malignancies, for example, renal malignancies, thyroid cancers, lung cancers, can lead to increase in procalcitonin levels. Therefore, we need to practise caution whenever we interpret procalcitonin levels in these conditions. Weak rise or no rise or false negatives can also happen, for example, early in the course of bacterial infections, or with atypical bacterial infection, for example chlamydia, syphilis, or mycobacterial infections. Procalcitonin can also be low in localised infections, for example, localised skin and soft tissue infections or bone and joint infections without systemic inflammatory response.
Additionally, in patients with multiple or large transfusion, even during bacterial infection and sepsis, you may see low procalcitonin levels because here we are measuring someone else’s blood. And finally, more studies are required for immunocompromised individuals, as the majority of published studies are small, heterogeneous in the inclusion criteria, and have addressed different study endpoints. What’s more, not all studies have shown positive findings with regards to procalcitonin and antimicrobial stewardship. And here I would like to share learning from a number of these studies. First of all, the PASS trial. This was an interventional study with the rationale to improve survival by early antibiotic intervention and escalation any time when procalcitonin is rising.
Although diagnostic and therapeutic measures were escalated in the procalcitonin guided intervention group, there was no outcome benefit. The lack of this effect, however, may be explained by an outbalance of the benefits of earlier treatment with the side effects due to escalated antibiotic therapy. The ProACT trial, which studied the effects of procalcitonin in lower respiratory tract infections in US hospitals, again failed to demonstrate any benefit of procalcitonin guidance. However, the study has a number of limitations, including poor adherence to algorithms and study protocols, and inclusion of patients with very low severity of disease and low likelihood of bacterial infections, plus other major limitations.
Daubin and colleagues investigated a procalcitonin algorithm to guide antibiotic treatment for chronic obstructive pulmonary disease patients admitted to intensive care for ventilator support. A higher three months mortality was observed in this study for the procalcitonin group. This increasing mortality was most prominent in patients who didn’t immediately get antibiotic treatment based on the study protocol. However, for patients who received antibiotics immediately, the outcome of the PCT group was non-inferior to the standard of care group. And finally, the HiTEMP study in emergency department patients with fever. Procalcitonin again didn’t reduce the prescription of antibiotics, but it was safe.
The trial, however, included hand selected patients with fever, including patients with no diagnostic uncertainties, example, patients with skin and soft tissue infections, intra-abdominal and urine tract infections, and so on. Additionally, higher procalcitonin cutoff levels more than 0.5 micrograms per litre was used in the emergency departments, contrary to prior published guidance and studies where they used 0.25 micrograms per litre. What I would like to say here is based on the HiTEMP study, which we discussed in the previous slide, if you have an obvious diagnosis of bacterial infection, like cellulitis in these cases, using procalcitonin wouldn’t alter your management. So in my view, it’s better not to waste valuable time and resources and treat these cases clinically.
I hope I have highlighted some of the limitations of procalcitonin test as well as a number of recently published studies when procalcitonin didn’t show additional benefit, at least from an antimicrobial stewardship point of view. Thank you.

In this video, Dr Kordo Saeed discusses the barriers and limitations of PCT.

Several barriers may prevent PCT from being used as a stewardship tool such as availability, cost and lack of trust. PCT also has several limitations which may make it less favourable. Not all PCT studies have positive outcomes and this video goes on to discuss the learnings taken from studies that have shown negative results. Finally, the video shows an example of using clinical judgement to steer a treatment plan, instead of PCT, showing that PCT should only be used when necessary and in the correct context.

Please refer to the see also section for more information and further reading on this topic.

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Procalcitonin: PCT as a Biomarker for Antimicrobial Stewardship

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