Lila Bouadma MD a, Charles-Edouard Luyt MD e, Florence Tubach MD b, Christophe Cracco MD f, Antonio Alvarez MD g, Carole Schwebel MD h, Frédérique Schortgen MD i, Sigismond Lasocki MD c, Prof Benoît Veber MD j, Monique Dehoux MD d, Maguy Bernard MD k, Blandine Pasquet MS b, Prof Bernard Régnier MD a, Prof Christian Brun-Buisson MD i, Prof Jean Chastre MD e *, Prof Michel Wolff MD a *, for the PRORATA trial group† The Lancet, Early Online Publication, 23 January 2010
Background
Reduced duration of antibiotic treatment might contain the emergence of multidrug-resistant bacteria in intensive care units. We aimed to establish the effectiveness of an algorithm based on the biomarker procalcitonin to reduce antibiotic exposure in this setting.

Methods
In this multicentre, prospective, parallel-group, open-label trial, we used an independent, computer-generated randomisation sequence to randomly assign patients in a 1:1 ratio to procalcitonin (n=311 patients) or control (n=319) groups; investigators were masked to assignment before, but not after, randomisation. For the procalcitonin group, antibiotics were started or stopped based on predefined cut-off ranges of procalcitonin concentrations; the control group received antibiotics according to present guidelines. Drug selection and the final decision to start or stop antibiotics were at the discretion of the physician. Patients were expected to stay in the intensive care unit for more than 3 days, had suspected bacterial infections, and were aged 18 years or older. Primary endpoints were mortality at days 28 and 60 (non-inferiority analysis), and number of days without antibiotics by day 28 (superiority analysis). Analyses were by intention to treat. The margin of non-inferiority was 10%. This trial is registered with ClinicalTrials.gov, number NCT00472667.

Findings
Nine patients were excluded from the study; 307 patients in the procalcitonin group and 314 in the control group were included in analyses. Mortality of patients in the procalcitonin group seemed to be non-inferior to those in the control group at day 28 (21·2% [65/307] vs 20·4% [64/314]; absolute difference 0·8%, 90% CI −4·6 to 6·2) and day 60 (30·0% [92/307] vs 26·1% [82/314]; 3·8%, −2·1 to 9·7). Patients in the procalcitonin group had significantly more days without antibiotics than did those in the control group (14·3 days [SD 9·1] vs 11·6 days [SD 8·2]; absolute difference 2·7 days, 95% CI 1·4 to 4·1, p<0·0001).

Interpretation
A procalcitonin-guided strategy to treat suspected bacterial infections in non-surgical patients in intensive care units could reduce antibiotic exposure and selective pressure with no apparent adverse outcomes.

Funding
Assistance Publique-Hôpitaux de Paris, France, and Brahms, Germany.

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