Procalcitonin-Guided Antibiotic Therapy

Gregory S. Martin, MD


April 09, 2010

Use of Procalcitonin to Reduce Patients' Exposure to Antibiotics in Intensive Care Units (PRORATA Trial): A Multicentre Randomised Controlled Trial

Bouadma L, Luyt CE, Tubach F, et al.
Lancet. 2010;375:463-474

Study Summary

Antimicrobial use is almost universal in critically ill patients, and microbial resistance in intensive care units (ICUs) has become a major factor influencing both resource utilization and patient outcomes. Recently, there has been increased interest in reducing the use of antimicrobial drugs in patients in the ICU by improving the diagnosis of infection or by shortening the duration of treatment. The current investigators randomly assigned adult patients with bacterial infections who were expected to be in the ICU for at least 3 days to antibiotic therapy guided by either standard clinical parameters or by serum procalcitonin (PCT) levels (< 80% of peak value or absolute < 0.5 µg/L to discontinue therapy). In this sample of 621 patients, mortality between the 2 groups was not different at day 28 (21.2% for PCT vs 20.4% for standard management) or at day 60 (30.0% vs 26.1%). Patients managed by PCT had an average of 2.7 fewer days of antibiotics than those in the control group. The investigators concluded that PCT-guided antibiotic therapy reduces antibiotic use in critically ill patients.


This study is not the first to examine the effect of using PCT to guide antibiotic use in critically ill patients.[1,2,3,4,5,6,7] However, it confirms the potential benefits observed in previous studies with respect to antibiotic use, and this study included more patients. Unfortunately, even a study of this size does not completely exclude adverse effects from PCT-guided therapy that shortens the duration of antibiotic administration. Why? An important concern with this study is that more than half (53%) of patients in the PCT-guided arm did not follow the protocol, and thus antibiotic use was not completely determined by PCT levels, as recommended.

From a safety perspective, 2 features require additional scrutiny. First is the significantly higher sequential organ failure assessment score at day 28 in the PCT group, and second is the rising mortality between days 28 and 60 in this group. Although patients apparently did not die of infectious causes, the deaths could have been related to infectious complications such as multiple organ dysfunction syndrome. In addition, the results of this trial cannot be generalized beyond the nonsurgical population that was studied, which is unfortunate because it is more difficult to adjudicate infection in patients in the surgical ICU, and they often receive prolonged antimicrobial therapy. The results of this study, which confirm the value of PCT to guide antibiotic use in critically ill patients, are highly encouraging. However, such a strategy cannot be recommended at present until additional studies confirm the safety of such a change and until this practice can be investigated in other groups of patients.