The use of procalcitonin to guide antibiotic therapy has been gradually increasing over the past several years – driven, in no small part, by increased recognition of the harms of antibiotic overuse. However, what evidence we have regarding its utility is primarily derived from manufacturer-sponsored trials – including virtual carpet-bombing of the literature by their sponsored representatives.
So, what happens when the manufacturer isn’t part of the trial?
No benefit.
This is the ProACT trial, an individual-randomized comparison between a procalcitonin-guided arm and “usual care” in patients with suspected lower respiratory tract infection for whom the indication for antibiotics is unclear. Physicians caring for patients randomized to the procalcitonin arm were provided results tied to antibiotic use recommendations – “strongly discouraged”, “discouraged”, “encouraged”, “strongly encouraged” – on initial presentation in the Emergency Department, and then in serial fashion for those admitted to the hospital. In those in the “usual care” arm, procalcitonin results were obtained, but not provided to the treating clinicians.
Then: Across 14 hospitals and 1,656 patients, there were no statistically significant differences between antibiotic-free days or adverse outcomes between the two arms. Done? Done.
Except, as skeptical as I might be regarding procalcitonin-guided therapy, there are big holes in these data as the definitive word on its disutility. Unlike other trials, these centers provided only passive guidance to clinicians regarding the procalcitonin algorithm. This resulted in only 72.9% of physicians adhering to protocol, with the greatest numbers of violations being antibiotic use in patients for whom it were discouraged, including 30% of those for whom antibiotic use was “strongly discouraged”:
Even though the “per-guideline” analysis also shows no difference, this is mostly because the bulk of the procalcitonin “per-guideline” population were those who appropriately received antibiotics – effectively eliminating the possibility of showing a difference in antibiotic use.
There are a few signals within these data reflecting the potential advantages of a procalcitonin-guided algorithm, should the protocol actually be followed. There were small differences in prescribing favoring the procalcitonin arm for almost every final clinical diagnosis – excepting about 15% absolute advantages for “acute bronchitis” and for those with non-specific diagnoses. It is likely these represented the cases for which the appropriateness of antibiotics was lowest, and probably also represent the majority of protocol violations. That said, one could easily make the argument this advantage only exists as a result of culturally-ingrained poor antibiotic prescribing habits for these sorts of borderline cases.
In short, these data clearly show there is no advantage to introducing procalcitonin into practice specifically in the fashion demonstrated here – but these cannot be generalized to say a different implementation or application of procalcitonin has no value. On the flip side, however, places that have implemented procalcitonin-driven stewardship programs also struggle with inappropriate and high-volume test ordering. There is work yet to be done for both proponents and skeptics of its value.
“Procalcitonin-Guided Use of Antibiotics for Lower Respiratory Tract Infection”
https://www.nejm.org/doi/full/10.1056/NEJMoa1802670