Clinical Question

Can using procalcitonin levels help guide antibiotic stewardship for patients with acute respiratory infections?

Evidence-Based Answer

Procalcitonin-guided antibiotic therapy, when compared with routine treatments, results in decreased mortality in patients with acute respiratory infections (absolute risk reduction [ARR] = 1.4%; number needed to treat [NNT] = 71). (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.) Compared with routine treatments, procalcitonin-guided antibiotic therapy also results in 2.4 fewer overall days of exposure to antibiotics and fewer overall antibiotic-related adverse effects (16% vs. 22% in the control group).¹ (Strength of Recommendation: B, based on inconsistent or limited-quality patient-oriented evidence.)

Practice Pointers

Acute respiratory infections are the most common reason for antibiotic therapy in primary care and hospital settings.^2–4 Appropriate treatment, including judicious use of antibiotics, is associated with improved clinical outcomes.^3–5 Procalcitonin is a calcitonin precursor whose serum levels rise in the setting of bacterial infection; procalcitonin-guided antibiotic therapy is already used in many clinical settings. This Cochrane analysis was designed to evaluate whether procalcitonin-guided antibiotic therapy for acute respiratory infections leads to improved outcomes vs. routine management. It is an update of a 2012 review.

The authors included 26 randomized controlled trials with a total of 6,708 patients who had acute respiratory infections.¹ Outcomes included all-cause mortality, treatment failure, and duration of antibiotic exposure. Per GRADE (grading of recommendations, assessment, development, and evaluation) criteria, the data in this review were deemed to be of high quality for mortality and antibiotic exposure outcomes. Data were deemed to be of moderate quality for treatment failure and adverse effects because the definitions for these end points among trials were not identical.

Compared with patients receiving routine care, those receiving procalcitonin-guided antibiotic therapy for acute respiratory infections were found to have lower 30-day all-cause mortality across all clinical settings (ARR = 1.4%; 95% confidence interval [CI], 0.5% to 2.4%; NNT = 71). Mortality is very low in primary care settings; therefore, assessment of this group was incomplete.

Treatment failure—defined as death, hospitalization, acute respiratory infection–specific complications (e.g., empyema for lower acute respiratory infections, meningitis for upper acute respiratory infections), recurrent or worsening infection, and participants reporting any symptoms of an ongoing respiratory infection (e.g., fever, cough, dyspnea) at follow-up—was not significantly lower in the procalcitonin group. Procalcitonin guidance was associated with a reduction in total antibiotic exposure (from a mean of 8.1 days to 5.7 days; regression coefficient = −2.4 days; 95% CI, −2.7 to −2.2; P < .001).

Data from six of the primary care and emergency department trials were analyzed and revealed a significant reduction in antibiotic-related adverse effects in patients whose care was guided by procalcitonin algorithms (16.3% in the procalcitonin-guided group vs. 22.1% in the control group; odds ratio = 0.68; 95% CI, 0.57 to 0.82; P < .001). Procalcitonin can be used quickly, with most in-house laboratories returning results within two hours. However, it may be cost prohibitive depending on insurance.

Appropriately timed and utilized procalcitonin-guided therapy has the potential to improve the management of patients with acute respiratory infections but has yet to be adequately studied in those with other clinical diagnoses. National guidelines do not yet mention the use of procalcitonin as part of the management of acute respiratory infections.