FPIN's Clinical Inquiries

Procalcitonin-Guided Antibiotic Therapy for Acute Respiratory Infections

 

Am Fam Physician. 2016 Jul 1;94(1):53-58.

Clinical Question

Is the use of a procalcitonin-guided antibiotic therapy algorithm safe and effective for reducing antibiotic use in patients with acute respiratory infections?

Evidence-Based Answer

A procalcitonin-guided antibiotic therapy algorithm should be used to decrease antibiotic use in adults with acute respiratory infections. (Strength of Recommendation [SOR]: A, based on a meta-analysis of multiple randomized controlled trials [RCTs].) The use of a procalcitonin-guided therapy algorithm reduces antibiotic use by 3.47 days without increasing morbidity or mortality in adults with acute respiratory infections. In the primary care setting, the use of procalcitonin-guided therapy algorithms decreases the rate of antibiotic prescription by 72% without affecting the risk of treatment failure. In children with lower respiratory tract infections, procalcitonin guidance should be used to reduce the duration of antibiotic therapy. (SOR: B, based on a single RCT.)

Evidence Summary

A Cochrane review and meta-analysis of 14 RCTs in primary care, emergency department, and intensive care unit settings included a total of 4,221 patients.1  In each trial, researchers randomized adults presenting with acute respiratory infections to procalcitonin-guided antibiotic therapy or standard care. All studies used a procalcitonin algorithm to guide antibiotic initiation (Table 1), and some also used the algorithm to guide discontinuation. Patients in the procalcitonin group received 3.47 fewer days of antibiotic treatment (95% confidence interval [CI], −3.78 to −3.17), with no difference in 30-day mortality (odds ratio [OR] = 0.94; 95% CI, 0.71 to 1.23) or treatment failure (OR = 0.82; 95% CI, 0.67 to 1.01).

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Table 1.

Recommendations for Procalcitonin-Guided Antibiotic Initiation in Adults with Acute Respiratory Infections

Procalcitonin level (μg per L)Recommendation

< 0.10

Bacterial infection highly unlikely; strongly recommend against antibiotics

0.10 to < 0.25

Bacterial infection unlikely; recommend against antibiotics

0.25 to 0.50

Bacterial infection likely; recommend antibiotics

> 0.50

Bacterial infection very likely; strongly recommend antibiotics


note: Algorithm for discontinuation of antibiotic therapy was more variable, with many studies recommending discontinuation when procalcitonin levels were decreased by 80% to 90% from baseline level or were < 0.25 μg per L.

Table 1.

Recommendations for Procalcitonin-Guided Antibiotic Initiation in Adults with Acute Respiratory Infections

Procalcitonin level (μg per L)Recommendation

< 0.10

Bacterial infection highly unlikely; strongly recommend against antibiotics

0.10 to < 0.25

Bacterial infection unlikely; recommend against antibiotics

0.25 to 0.50

Bacterial infection likely; recommend antibiotics

> 0.50

Bacterial infection very likely; strongly recommend antibiotics


note: Algorithm for discontinuation of antibiotic therapy was more variable, with many studies recommending discontinuation when procalcitonin levels were decreased by 80% to 90% from baseline level or were < 0.25 μg per L.

The authors of the Cochrane review performed multiple sensitivity analyses that excluded trials from the intensive care unit, trials with the potential for significant bias, and trials with poor adherence to the algorithm. The analyses yielded similar results, suggesting that the findings are robust. Results were similar when stratified by treatment setting and by type of respiratory infection (upper respiratory infections including the common cold, rhinosinusitis, otitis, tonsillitis, and pharyngitis, and lower respiratory tract infections including community-, hospital-, and ventilator-acquired pneumonia and bronchitis). A major limitation was relatively short follow-up; most studies reported outcomes at 30 days, whereas some reported outcomes only to hospital discharge. The long-term risks and benefits of decreased antibiotic usage were not assessed. All of the studies were under-powered to address mortality. Of note, six of the 14 studies included significant funding from the manufacturer of the procalcitonin laboratory assay, and all were conducted in Europe, where baseline prescribing practices may be different than in the United States.

A study in Swiss primary care practices randomized adults with acute respiratory infections (n = 458) to treatment directed by a procalcitonin-guided algorithm vs. standard care.2 Patients in the procalcitonin group received antibiotics 72% less often than those who received standard care (95% CI, 66% to 78%). There was no difference in the risk of ongoing or relapsing symptoms at 28 days (OR = 1.0; 95% CI, 0.7 to 1.5) or days of restricted activity in the two weeks after randomization (8.7 vs. 8.6; mean difference = 0.1; 95% CI, −0.6 to 0.8). In a similar RCT of 550 patients presenting to German primary care clinics with acute respiratory tract infections, antibiotics were prescribed 41.6% less often in the procalcitonin algorithm group, with no difference between groups in the number of days of significant health impairment (9.04 vs. 9.00; mean difference = 0.04; 95% CI, −0.73 to 0.81).3

An RCT in Switzerland evaluated procalcitonin algorithms in 337 children (mean age = 3.8 years) with lower respiratory tract infections presenting to pediatric emergency departments.4 There was no difference in antibiotic prescription rates in the procalcitonin and control groups (OR = 1.26; 95% CI, 0.81 to 1.95), but there was a shorter mean duration of antibiotic use in the procalcitonin group (−1.8 days; 95% CI, −3.5 to −0.5).

Recommendations from Others

In 2012, the Agency for Healthcare Research and Quality conducted an independent systematic review and found that procalcitonin guidance reduced antibiotic prescription rates and the duration of antibiotic therapy without increasing morbidity or mortality.5 The review noted that most studies were conducted using quantitative procalcitonin assays, which take several hours to run and are not available at the point of care.

Copyright Family Physicians Inquiries Network. Used with permission.

Address correspondence to Carl Morris, MD, MPH, at morris.cg@ghc.org. Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

REFERENCES

show all references

1. Schuetz P, Müller B, Christ-Crain M, et al. Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Cochrane Database Syst Rev. 2012;(9):CD007498....

2. Briel M, Schuetz P, Mueller B, et al. Procalcitonin-guided antibiotic use vs a standard approach for acute respiratory tract infections in primary care. Arch Intern Med. 2008;168(18):2000–2007.

3. Burkhardt O, Ewig S, Haagen U, et al. Procalcitonin guidance and reduction of antibiotic use in acute respiratory tract infection. Eur Respir J. 2010;36(3):601–607.

4. Baer G, Baumann P, Buettcher M, et al. Procalcitonin guidance to reduce antibiotic treatment of lower respiratory tract infection in children and adolescents (Pro-PAED): a randomized controlled trial. PLoS One. 2013;8(8):e68419.

5. Soni NJ, Samson DJ, Galaydick JL, Vats V, Pitrak DL, Aronson N. Procalcitonin-guided antibiotic therapy: executive summary. Comparative Effectiveness Review No. 78. Rockville, Md.: Agency for Healthcare Research and Quality; 2012. AHRQ publication no. 12(13)-EHC 124-EF.

Clinical Inquiries provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group ( http://www.cebm.net/?o=1025).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to http://www.fpin.org or e-mail: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, Assistant Medical Editor.

A collection of FPIN's Clinical Inquiries published in AFP is available at http://www.aafp.org/afp/fpin.

 

 

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