Effect of procalcitonin-based guidelines compared with standard guidelines on antibiotic use in lower respiratory tract infections: the randomized-controlled multicenter ProHOSP trial

Introduction

In previous smaller trials, a procalcitonin algorithm reduced antibiotic use in patients with lower respiratory tract infections. However, the feasibility and safety of this approach in a multicenter setting has not been demonstrated.

Methods

We enrolled 1,359 consecutive patients with lower respiratory tract infections admitted to emergency departments of six tertiary-care hospitals in Switzerland. Patients were randomized to administration of antibiotics based on a procalcitonin algorithm with predefined cutoff ranges for initiating or stopping antibiotics (procalcitonin group) or according to standard guidelines (control group). Procalcitonin was measured locally in each hospital and instructions were web-based. The primary endpoint of this noninferiority trial was the composite adverse outcome of death, ICU admission, disease-specific complications or recurrent infection requiring antibiotic treatment within 30 days.

Results

The rate of overall adverse outcomes was similar in the procalcitonin and the control group (15.5% vs. 18.9%; difference -3.4%, 95% CI = -7.5% to 0.5%). In the procalcitonin group, antibiotic exposure (that is, number of days on antibiotics per patient) was significantly lower as compared with the control group overall (34.8% reduction, P < 0.001), and in subgroups of patients with community-acquired pneumonia (n = 925, 32.4% reduction), exacerbation of chronic obstructive pulmonary disease (n = 228, 50.4% reduction) and acute bronchitis (n = 151, 65.0% reduction). Antibiotic-associated side effects were less frequent in the procalcitonin group as compared with the control group (19.8% vs. 28.1%; P < 0.001).

Conclusion

In this multicenter setting, without increasing the rate of adverse outcomes, procalcitonin guidance markedly reduced antibiotic exposure and antibiotic-associated side effects in patients with lower respiratory tract infections.

Trial Registration

ClinicalTrials.gov identifier NCT00350987.