This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200708-1238OCv1 177/5/498    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nobre, V. Articles by Pugin, J. Search for Related Content PubMed PubMed Citation Articles by Nobre, V. Articles by Pugin, J.

Use of Procalcitonin to Shorten Antibiotic Treatment Duration in Septic Patients

A Randomized Trial

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

Correspondence and requests for reprints should be addressed to Prof. Jérôme Pugin, M.D., Intensive Care, University Hospital of Geneva, 24, Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail: jerome.pugin{at}medecine.unige.ch

Rationale: The duration of antibiotic therapy in critically ill patients with sepsis can result in antibiotic overuse, increasing the risk of developing bacterial resistance.

Objectives: To test the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in 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% or more from the initial value (if clinicians agreed) but not before Day 3 (if baseline PCT levels were <1 µg/L) or Day 5 (if baseline PCT levels were 1 µg/L). In control patients, clinicians decided on the duration of antibiotic therapy based on empirical rules.

Measurements and Main Results: Patients assigned to the PCT group had 3.5-day shorter median duration of antibiotic therapy for the first episode of infection than control subjects (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 intensive care unit stay was also observed in patients assigned to the PCT group (P = 0.03).

Conclusions: 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 registered with www.clinicaltrials.gov (NCT 00250666).

Key Words: procalcitonin • sepsis • intensive care • antibiotics • controlled trial

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject The duration of antibiotic therapy in critically ill patients with sepsis is based on empirical rules, which may lead to antibiotic overuse and selection pressure. What This Study Adds to the Field The application of a decision algorithm based on plasma procalcitonin levels can significantly shorten the duration of antibiotic therapy and intensive care unit stay, without apparent harm to patients with severe sepsis and septic shock.

 

This article has been cited by other articles:

				D. Stolz, N. Smyrnios, P. Eggimann, H. Pargger, N. Thakkar, M. Siegemund, S. Marsch, A. Azzola, J. Rakic, B. Mueller, et al. Procalcitonin for reduced antibiotic exposure in ventilator-associated pneumonia: a randomised study Eur. Respir. J., December 1, 2009; 34(6): 1364 - 1375. [Abstract] [Full Text] [PDF]

				K. M. Kuper, E. B. Hirsch, V. H. Tam, and on behalf of the Houston Infectious Diseases Netwo Significant publications on infectious diseases pharmacotherapy in 2008 Am. J. Health Syst. Pharm., October 1, 2009; 66(19): 1726 - 1734. [Abstract] [Full Text] [PDF]

				P. Schuetz, M. Christ-Crain, R. Thomann, C. Falconnier, M. Wolbers, I. Widmer, S. Neidert, T. Fricker, C. Blum, U. Schild, et al. Effect of Procalcitonin-Based Guidelines vs Standard Guidelines on Antibiotic Use in Lower Respiratory Tract Infections: The ProHOSP Randomized Controlled Trial JAMA, September 9, 2009; 302(10): 1059 - 1066. [Abstract] [Full Text] [PDF]

				J. Struck, M. Strebelow, S. Tietz, C. Alonso, N. G. Morgenthaler, J. G. van der Hoeven, P. Pickkers, and A. Bergmann Method for the Selective Measurement of Amino-Terminal Variants of Procalcitonin Clin. Chem., September 1, 2009; 55(9): 1672 - 1679. [Abstract] [Full Text] [PDF]

				R. A. Fowler, N. K. J. Adhikari, D. C. Scales, W. L. Lee, and G. D. Rubenfeld Update in Critical Care 2008 Am. J. Respir. Crit. Care Med., May 1, 2009; 179(9): 743 - 758. [Full Text] [PDF]

				K. L. Lawrence and M. H. Kollef Antimicrobial Stewardship in the Intensive Care Unit: Advances and Obstacles Am. J. Respir. Crit. Care Med., March 15, 2009; 179(6): 434 - 438. [Abstract] [Full Text] [PDF]

				D. N. Schwartz Procalcitonin-Guided Antibiotic Use vs a Standard Approach for Acute Respiratory Tract Infections in Primary Care Arch Intern Med, October 13, 2008; 168(18): 2007 - 2008. [Full Text] [PDF]

				L. B. Ware Clinical Year in Review IV: Acute Respiratory Distress Syndrome, Radiology in the Intensive Care Unit, Nonpulmonary Critical Care, and Pulmonary Infections in the Immunocompromised Host Proceedings of the ATS, September 15, 2008; 5(7): 755 - 760. [Full Text] [PDF]

				Sepsis, Procalcitonin Levels, and Duration of Antibiotics Journal Watch Infectious Diseases, March 19, 2008; 2008(319): 4 - 4. [Full Text]