Early antibiotic administration is a critical step in appropriate sepsis care. However, overuse and misuse of antibiotics, including the unnecessarily prolonged use of antibiotics, can have adverse effects and lead to increased microbial resistance.

A Comparative Effectiveness Review released in October of 2012 by the Agency of Healthcare Research and Quality (AHRQ) examined the use of procalcitonin as a biomarker of systemic infection, and specifically its use in guiding the early discontinuation of antibiotics. Eighteen randomized control trials comparing procalcitonin guidance with the use of clinical criteria to manage antibiotic therapy in patients with known or suspected infection were reviewed for this report.

Procalcitonin is a precursor of the hormone calcitonin, which is involved in calcium homeostatis, and is released by the parafollicular C-cells of the thyroid and the neuroendocrine cells of the lung and intestine. It has been known for some time that procalcitonin levels rise markedly in inflammatory conditions, particularly those associated with bacterial infections. Levels of procalcitonin are virtually undetectable in healthy people, but in systemic infections such as sepsis, they are generally greater than 0.5-2 ng/mL, and often reach levels of 10 ng/mL or higher. A level higher than 0.25 ng/mL has been suggested as a cutoff value predictive of bacterial respiratory infection requiring antibiotics, whereas a lower level signals resolution of the infection.

The AHRQ report concluded that procalcitonin guidance reduces antibiotic use when used to discontinue antibiotics in the following populations:

  1. Adult ICU patients (high level of evidence)
  2. Patients with respiratory tract infections (high level of evidence)
  3. Neonates with suspected neonatal sepsis (moderate level of evidence)

Evidence was insufficient to draw conclusions in children 1-36 months of age with fever of unknown source and in use of preemptive antibiotics after surgery. Immunocompromised patients and other special populations were excluded from the studies examined in this report.

Procalcitonin guidance did not increase morbidity (moderate evidence) or mortality (low evidence) among adult ICU patients or patients with respiratory tract infections. In the neonatal sepsis population there was insufficient evidence on morbidity and mortality outcomes.

Complete details of the AHRQ report may be found here.


Daniel Nichita, MD
The Escavo Team