Introduction: With rising global antibiotic resistance,
stewardship programs aimed at controlling multi-drug resistant (MDR) pathogens
have begun to gain acceptance. These programs stress appropriate antibiotic
selection, dosage and duration. A growing literature suggests serum
procalcitonin (PCT) levels may be useful in guiding antibiotic duration and
de-escalation. This report sought to evaluate the evidence-based data available
from prospective randomized controlled trials (RCT) on the role of PCT in guiding
reductions in antibiotic duration in adult sepsis patients. Methods: A
comprehensive search of all published prospective RCT(s) on the use of PCT as a
tool for guiding antibiotic therapy in adult sepsis patients was conducted
using PubMed, Medline Plus and Google Scholar (2007-2013). Keywords searched
included, “procalcitonin”, “sepsis-therapy”, “sepsis biomarker”, “antibiotic
duration”, “drug de-escalation”, and “antimicrobial stewardship”. Results: Four RCT(s) involving 826 adult sepsis
patients have evaluated the role of serum PCT levels to guide criteria for
cessation of antibiotic therapy based either on specific PCT levels or PCT
kinetics. Bouadma et al. (N = 621) stopped antibiotics when the PCT
concentration was <80% of the peak PCT value, or the absolute PCT
concentration was <0.5 μg/L. The PCT arm showed a 2.7-day reduction in
antibiotics. Schroeder et al. (N = 27) discontinued antibiotics if
clinical signs of infection improved and the PCT value decreased to <1 ng/mL
or to <35% of the initial value within three days. The PCT arm had a 1.7-day
reduction in antibiotics. Hochreiter et al. (N = 110) ceased antibiotics when the PCT
decreased to <1 ng/mL, or to 25% - 35% of the initial value over three days
if the value was >1 ng/mL. The PCT arm showed a 2-day reduction in
antibiotics. Finally, Nobre et al. (N = 68) stopped antibiotics when PCT
levels decreased by 90% or more from the initial value, but not prior to Day 3
(if baseline PCT measured <1 μg/L) or Day 5 (if baseline PCT measured ≥1
μg/L). The PCT arm showed a 4-day reduction in antibiotics. Overall, reduction
of PCT levels to 10% - 35% of the initial concentration, to <80% of the peak
PCT value, or to an absolute PCT value of <1 μg/L warranted antibiotic
discontinuation 1.7 to 4 days earlier. No study reported a significant
difference in mortality between the PCT arm and the control arm (p< 0.05). Conclusions: PCT-guided early cessation of
antibiotic therapy in adult sepsis patients is associated with a significant
decrease in antibiotic days, with no effect on overall mortality. Measurement
of serum PCT levels may have a role in antimicrobial stewardship programs aimed
at limiting antibiotic therapy duration, decreasing the selective pressure on
drug-resistant bacterial strains and reducing hospital costs.