Study Design Summary: Multicenter study of 630 patients split evenly into intervention and control groups, with suspected bacterial infections, looking at 28 and 60 day mortality (non-inferiority analysis) as well as antibiotic exposure between the two groups (superiority analysis).
Notes: Patients were eligible if they were not receiving antibiotics prior to enrollment or receiving antibiotics for less than 24 hours prior to enrollment if they were included in the study less than 12 hours after admission. Prespecified algorithms advised clinicians on whether to start antibiotics and when they should be stopped. In patients who got antibiotics, procalcitonin levels were assessed daily.
Groups were well balanced in all aspects including age, SOFA score, biomarker levels such as procalcitonin and lactate at time of enrollment, infection site. Both groups had equal numbers of documented versus suspected infections as well as appropriate antimicrobial coverage.
Both groups had similar 28 day mortality, higher mortality in the procalcitonin group at 60 days (30% vs 26%), but “no patient in either group who died during days 29–60 had an infection relapse, and most deaths resulted from complications directly related to the severity of underlying disease.” Procalcitonin group had roughly 3 more days without antibiotics. There was a silightly higher relapse and superinfection rate in the procalcitonin group, with LOS in ICU and hospital same for both groups. There was not a between-group difference for the rates of emerging multidrug-resistant bacteria.
There was a significant amount of protocol deviation in both groups which makes the data hard to interpret. “53% of patients randomised to the procalcitonin group were not given algorithm-guided treatment.” Procalcitonin cutoffs between studies has been highly variable thus making interpretion of the studies together also difficult.
Study Conclusion: Procalcitonin- guided antibiotic treatment substantially lowers antibiotic exposure and is non-inferior to standard care with respect to outcomes.
Fusion Beat Bottom Line Impression: The high amount of protocol deviation makes the data very difficult to interpret and I do not think this study provides practice changing evidence that procalcitonin guided strategies reduce antibiotic exposure or affect mortality in either way. Also given the fact that studies are heterogeneous in their procalcitonin cutoffs, it makes the overall data difficult to interpret and thus not practice changing. However, I do think that adding in procalcitonin trends as another data point to evaluate whether a patient needs to start/stop antibiotics can likely be helpful.
While some may argue that the antibiotics exposure was reduced but overall mortality and resistant organism rates were not changed, with increased relapse and superinfection rates in the procalcitonin group, adding in a biomarker such as procalcitonin as part of the whole picture and reducing time on antibiotics is helpful in and of itself as prolonged exposures to unnecessary antibiotics portends itself to increase risk of unwanted sided effects.
A Fusion Beat 