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Published ahead of print on April 7, 2006, doi:10.1164/rccm.200512-1922OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 1, July 2006, 84-93

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Submitted on December 17, 2005
Accepted on April 6, 2006

Procalcitonin-Guidance of Antibiotic Therapy in Community-Acquired Pneumonia - A Randomized Trial

Mirjam Christ-Crain1*, Daiana Stolz2, Roland Bingisser3, Christian Muller4, David Miedinger2, Peter R Huber5, Werner Zimmerli6, Stephan Harbarth7, Michael Tamm2, and Beat Muller1

1 Department of Internal Medicine, University Hospital, Basel, Switzerland; Department of Endocrinology, University Hospital, Basel, Switzerland, 2 Department of Pneumology, University Hospital, Basel, Switzerland, 3 Department of Emergency Medicine, University Hospital, Basel, Switzerland, 4 Department of Internal Medicine, University Hospital, Basel, Switzerland, 5 Department of Clinical Chemistry, University Hospital, Basel, Switzerland, 6 Medical University Clinic, Kantonsspital, Liestal, Switzerland, 7 Division of Hospital Epidemiology, University Hospital, Geneva, Switzerland

* To whom correspondence should be addressed. E-mail: christmj{at}bluewin.ch.

Rationale: In patients with community-acquired pneumonia, guidelines recommend antibiotic treatment for 7 to 21 days. Procalcitonin is elevated in bacterial infections, and its dynamics have prognostic implications. Objective: To assess procalcitonin guidance for the initiation and duration of antibiotic therapy in community-acquired pneumonia. Methods: In a randomized intervention trial, 302 consecutive patients with suspected community-acquired pneumonia were included. Data were assessed at baseline, at days 4, 6 and 8 and after 6 weeks. The control group (n=151) received antibiotics according to usual practice. In the procalcitonin group (n=151), antibiotic treatment was based on serum procalcitonin concentrations as follows: strongly discouraged <0.1µg/L; discouraged <0.25µg/L; encouraged >0.25µg/L; strongly encouraged >0.5µg/L. Primary endpoint was antibiotic use; secondary endpoints were measures of clinical, laboratory and radiographic outcome. Results: At baseline, both groups were similar with regards to clinical, laboratory and microbiology characteristics, and Pneumonia Severity Index (PSI). Procalcitonin-guidance reduced total antibiotic exposure (relative risk, 0.52; 95 % confidence interval [CI] 0.48-0.55; P<0.001), antibiotic prescriptions on admission (85 versus 99 %; P<0.001) and antibiotic treatment duration (median, 5 versus 12 days; P<0.001) compared to patients treated according to guidelines. After adjustment for PSI, the hazard ratio of antibiotic discontinuation was higher in the procalcitonin group than in the control group (3.2, 95 % CI 2.5 to 4.2). Outcome was similar in both groups with an overall success rate of 83 %. Conclusions: Procalcitonin-guidance substantially reduces antibiotic use in community-acquired pneumonia. These findings may have important clinical and public-health implications.
Key words: community-acquired pneumonia, antibiotic therapy, procalcitonin




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