Evdoxia Kyriazopoulou 1 , Lydia Liaskou-Antoniou 1 , George Adamis 2 , Antonia Panagaki 1 , Nikolaos Melachroinopoulos 1 , Elina Drakou 2 , Konstantinos Marousis 2 , Georgios Chrysos 3 , Andronikos Spyrou 2 , Nikolaos Alexiou 4 , Styliani Symbardi 4 , Zoi Alexiou 5 , Styliani Lagou 6 , Virginia Kolonia 7 , Theologia Gkavogianni 1 , Miltiades Kyprianou 1 , Ioannis Anagnostopoulos 6 , Garyfallia Poulakou 6 , Malvina Lada 7 , Anna Makina 5 , Efrosyni Roulia 5 , Marina Koupetori 4 , Vasileios Apostolopoulos 4 , Dimitra Petrou 4 , Thomas Nitsotolis 3 , Anastasia Antoniadou 1 , Evangelos J. Giamarellos-Bourboulis , 1
15 January 2021
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).