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Published ahead of print on December 20, 2007, doi:10.1164/rccm.200708-1238OC

Am. J. Respir. Crit. Care Med., Volume 177, Number 5, March 2008, 498-505

A more recent version of this article appeared on March 1, 2008
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Submitted on August 22, 2007
Accepted on December 20, 2007

Use of Procalcitonin to Shorten Antibiotic Treatment Duration in Septic Patients. A Randomized Trial

Vandack Nobre1, Stephan Harbarth2, Jean-Daniel Graf3, Peter Rohner4, and Jerome Pugin1*

1 Intensive Care, University Hospitals of Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland, 2 Infection Control Program, University Hospitals of Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland, 3 Central Chemistry Laboratory, University Hospitals, University Hospitals of Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland, 4 Microbiology Laboratory, University Hospitals of Geneva, Faculty of Medicine, University of Geneva, Geneva, Switzerland

* To whom correspondence should be addressed. E-mail: jerome.pugin{at}medecine.unige.ch.

Rationale and objective: To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows to reduce the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in patients with severe sepsis and septic shock. Methods: In patients randomly assigned to the intervention group, antibiotics were stopped when PCT levels had decreased ≥ 90% from the initial value - if clinicians agreed to - but not before day 3 (if baseline PCT levels < 1µg/L) or day 5 (if baseline PCT levels ≥1µg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules. Main Results: Patients assigned to the PCT group had 3.5 days shorter median duration of antibiotic therapy for the first episode of infection than controls (intention-to-treat, n = 79, p = 0.15). In patients in whom a decision could be taken based on serial PCT measurements, PCT guidance resulted in a 4-day reduction in the duration of antibiotic therapy (per-protocol, n = 68, p = 0.003) and a smaller overall antibiotic exposure (p = 0.0002). A similar mortality and recurrence of the primary infection were observed in PCT and control groups. A 2-day shorter ICU stay was also observed in patients assigned to the PCT group (p = 0.03). Conclusion: Our results suggest that a protocol based on serial PCT measurement allows reducing antibiotic treatment duration and exposure in patients with severe sepsis and septic shock without apparent harm. Clinical Trial Registry Information: ID# NCT00250666 registered at www.clinicaltrials.gov
Key words: procalcitonin, sepsis, intensive care, antibiotics, controlled trial




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