The advent of antibiotic therapy has led to dramatic reductions in mortality and morbidity due to bacterial infections and sepsis. The overuse of antibiotics to treat infections, however, may expose patients to adverse events resulting from use of these agents and by increasing the risk of developing bacterial resistance. To fight the emergence of bacterial resistance to antimicrobial agents, more effective efforts are needed to reduce the inappropriate or unnecessarily prolonged use of antibiotics.

A novel approach for determining the need and optimal duration of antibiotic therapy is to use biomarkers of bacterial infections (see also, Procalcitonin: A Biomarker for Early Sepsis Intervention). One such biomarker is procalcitonin (PCT), which has been shown to become up-regulated during bacterial infections. It also appears to mirror the extent and severity of infections. Measuring PCT levels may help physicians more rationally decide on prescriptions and duration of antibiotic therapy in patients with infections. Previous studies have suggested that using clinical algorithms based on PCT levels results in less antibiotic use without negatively affecting clinical outcomes. However, various trials using such algorithms have been conducted largely in European healthcare settings.

New Data from Procalcitonin Algorithms

In the August 8, 2011 Archives of Internal Medicine, my colleagues and I performed a systematic review of 14 randomized controlled trials that investigated PCT algorithms for antibiotic treatment decisions in adults with respiratory tract infections and sepsis from primary care, ED, and ICU settings. The aim was to summarize the evidence for using PCT measurements and to propose clinical algorithms for use in future trials in the United States. Our analysis revealed no significant differences in mortality between PCT groups and control groups (7.7% vs 8.3%, respectively). A consistent reduction in the range of 25% to 75% was observed in antibiotic prescription and/or duration of therapy. This was primarily because of lower prescribing rates in low-acuity primary care and ED patients and a shorter duration of therapy in moderate- and high-acuity ED and ICU patients (see also, Sepsis Care Improved in the ED).

“Measuring PCT levels may help physicians more rationally decide onprescriptions and duration of antibiotic therapy in patientswith infections.”

Philipp Schuetz, MD, MPH

It appears that measuring PCT levels for antibiotic decisions in patients with respiratory tract infections and sepsis can help reduce antibiotic exposure without worsening the mortality rate. While the algorithms assessed from the studies in our investigation varied, a few commonalities were identified. In most studies, PCT values were used to continue or discontinue antibiotic treatment that already was initiated. A decrease in raised PCT levels appeared to correlate adequately with the resolution of bacterial infections, allowing for the safe discontinuation of antibiotic therapy. This was true even if discontinuation of antibiotics occurred before the traditional length of an antibiotic course had elapsed. In lower-acuity settings or in infections that are less dangerous, PCT values can be used to help clinicians determine if antibiotics should be prescribed initially. Importantly, all patients should undergo reassessment in a clinically appropriate timeframe. In high-risk or ICU patients with suspected sepsis, empirical antibiotic therapy should not be delayed for PCT measurement.

Procalcitonin’s Role Moving Forward

There is hope that in the future, more literature will emerge about the role of PCT in the U.S. In the meantime, clinicians should recognize that the currently available algorithms for PCT use, much like those for other biomarkers, should supplement rather than supplant clinical impressions.

References

Schuetz P, Chiappa V, Briel M, Greenwald JL. Procalcitonin algorithms for antibiotic therapy decisions: a systematic review of randomized controlled trials and recommendations for clinical algorithms. Arch Intern Med. 2011;171:1322-1331. Available at: http://archinte.ama-assn.org/cgi/content/full/171/15/1322.

Schuetz P, Christ-Crain M, Müller B. Procalcitonin and other biomarkers to improve assessment and antibiotic stewardship in infections: hope for hype? Swiss Med Wkly. 2009;139:318-326.

Yealy DM, Fine MJ. Measurement of serum procalcitonin: a step closer to tailored care for respiratory infections? JAMA. 2009;302:1115-1116.

Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. 2007;7:210-217.

Nobre V, Harbarth S, Graf J-D, et al. Use of procalcitonin to shorten antibiotic treatment duration in septic patients: a randomized trial. Am J Respir Crit Care Med. 2008;177:498-505.

Kopterides P, Siempos II, Tsangaris I, et al. Procalcitonin-guided algorithms of antibiotic therapy in the intensive care unit: a systematic review and meta-analysis of randomized controlled trials. Crit Care Med. 2010;38:2229-2241.

Tang H, Huang T, Jing J, et al. Effect of procalcitonin-guided treatment in patients with infections: a systematic review and meta-analysis. Infection. 2009;37:497-507.