ArticlesUse of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial
Introduction
Antimicrobial resistance has emerged as a major factor affecting patient outcomes and overall resources in intensive care units.1 We are now heading towards extreme drug resistance, especially among gram-negative bacilli.1, 2, 3 Insufficient measures to control infection and selective antibiotic pressure are two key factors associated with the emergence of bacterial resistance.4 Compelling evidence that antibiotic use causes resistance has led to calls to stop inappropriate prescription of antibiotics.4, 5
Antimicrobial consumption in the intensive care unit can be substantially reduced by starting of antibiotics only for patients with true bacterial infections, or shortening of treatment duration for those needing antibiotics, or both.4, 5, 6, 7 Guidance for duration of antibiotic treatment could be based on the results of studies comparing two different durations,8, 9, 10 but such studies are still scarce for patients in intensive care units, and are applicable only for well defined infection sites. Another approach is to identify easily obtainable biomarkers, in addition to usual clinical and bacteriological indicators, to guide physicians. The potential advantage of such a strategy would be to individualise antibiotic duration according to the patient's response to antimicrobial treatment.
Procalcitonin, a calcitonin precursor hormone, is judged to be a fairly specific marker for severe bacterial infection in patients with suspected sepsis.11, 12, 13 Guidance about serum procalcitonin concentration has substantially reduced antibiotic use in patients presenting at the emergency department or admitted to hospital for lower-respiratory-tract infections.14, 15, 16, 17 Despite these encouraging results, the potential usefulness of procalcitonin as an instrument to guide antibiotic use in all intensive care units has not yet been shown. Results from two small studies, each in one centre, have suggested that a protocol based on serial serum procalcitonin measurements could achieve shortening of antibiotic treatment by 2–3·5 days for patients in the intensive care unit with sepsis or septic shock.18, 19
We therefore undertook a randomised, multicentre effectiveness trial to assess the benefit of procalcitonin to help physicians start, continue, or stop antibiotics for patients in intensive care units with suspected bacterial infections. Our objective was to establish whether a strategy based on procalcitonin concentration would achieve reduced antibiotic consumption. Because shortening of antibiotic treatment might be harmful, our trial was designed to assure that this strategy did not affect outcome.
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Study design and participants
The prospective, parallel-group, open-label PROcalcitonin to Reduce Antibiotic Treatments in Acutely ill patients (PRORATA) trial was undertaken in France between June, 2007, and May, 2008. We assessed critically ill patients with suspected bacterial infections in seven (five medical, two surgical) intensive care units in five university-affiliated hospitals, and one medicosurgical intensive care unit in a general hospital; in total these units comprised 140 beds.
All adults with suspected
Results
1315 patients with suspected infections were screened for eligibility, of whom 630 were enrolled and randomly assigned to the procalcitonin group (n=311 patients) or the control group (n=319; figure 2). Four patients in the procalcitonin group and five in the control group were subsequently excluded from the analysis. Table 1 and webappendix pp 4–5 show the clinical characteristics of the remaining 621 patients at admission to the intensive care unit and inclusion into the study. For patients
Discussion
The results of our study show that for patients with suspected infections, either at admission to the intensive care unit or during their stay in the unit, procalcitonin-guided antibiotic treatment substantially lowers antibiotic exposure and is non-inferior to standard care with respect to outcomes. For patients in the procalcitonin group, the absolute difference of 2·7 days between the mean numbers of days without antibiotics by day 28 corresponds to a 23% relative reduction in antibiotic
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