Procalcitonin to Reduce Long-Term Infection-associated Adverse Events in Sepsis. A Randomized Trial
Evdoxia Kyriazopoulou, Lydia Liaskou-Antoniou, George Adamis, Antonia Panagaki, Nikolaos Melachroinopoulos, Elina Drakou, Konstantinos D. Marousis, Georgios Chrysos, Andronikos Spyrou, Nikolaos Alexiou, Styliani Symbardi, Zoi Alexiou, Styliani Lagou, Virginia Kolonia, Theologia Gkavogianni, Miltiades Kyprianou, Ioannis Anagnostopoulos, Garyphallia Poulakou, Malvina Lada, Anna Makina, Efrosyni Roulia, Marina Koupetori, Vasileios Apostolopoulos, Dimitra Petrou, Thomas Nitsotolis, Anastasia Antoniadou, Evangelos J. Giamarellos‐Bourboulis
Abstract
Abstract Rationale Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear. Objectives To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis. Methods In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization. Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8–13.1%; 9/125) versus 15.3% (95% CI, 10.1–22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20–0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10–22.5%; 19/125) versus 28.2% (95% CI, 21.2–36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29–0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5–7) versus 10 (range, 7–15) days (P < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm. Conclusions In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization. Clinical trial registered with www.clinicaltrials.gov (NCT03333304).