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 greater than or equal to 80% reduction in PCT levels or any PCT less than or equal to 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 less than 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.
At a Glance Commentary
Scientific Knowledge on the Subject
The procalcitonin (PCT)-guided discontinuation of antibiotic therapy was demonstrated to reduce antibiotic exposure in patients with lower respiratory tract infections and/or sepsis in several randomized trials. However, the effect on the incidence of infections by resistant microorganisms has not been studied.
What This Study Adds to the Field
The PROGRESS (Procalcitonin-guided Antimicrobial Therapy to Reduce Long-Term Sequelae of Infections) trial was designed as a real-world pragmatic trial, enrolling patients with sepsis. The trial demonstrated that PCT-guided antimicrobial treatment in sepsis was effective in reducing infection-associated adverse events like infections by multidrug-resistant organisms and Clostridioides difficile, as well as in-hospital and 28-day mortality. Generated evidence implicates that PCT guidance in sepsis is a safe strategy with long-term benefits that may have a substantial impact on public health, particularly for countries with high baseline antimicrobial consumption.
Here is a related editorial in the same issue.
Since pneumonia patients were included in the study, do these results contradict the recommendations of the community acquired pneumonia guidelines? The idea that procalcitonin levels should not be measured in patients with community-acquired pneumonia is a popular misconception of the guidelines, often promulgated via institutional pathways. All the guideline says is that if clinical judgement leads to a diagnosis of pneumonia antimicrobial treatment should be initiated regardless of the initial procalcitonin result. The guideline does not preclude calcitonin guided therapy.