Objectives:

To systematically review comparative studies of the use of procalcitonin in the clinical management of adult and pediatric patients with suspected local or systemic infection.

Data sources:

MEDLINE^®, Embase^®, the Cochrane Database of Systematic Reviews, National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme were searched from January 1, 1990, to December 16, 2011; the MEDLINE, Embase, and Cochrane searches were updated in December 2011. A search of the gray literature included databases with regulatory information, clinical trial registries, abstracts and conference papers, grants and federally funded research, and information from manufacturers.

Review methods:

We sought studies that compared procalcitonin-guided versus clinical-criteria-guided initiation, discontinuation, or change of antibiotic therapy. Outcomes were antibiotic use, mortality, morbidity, and adverse drug events of antibiotic therapy. Data were abstracted by a single reviewer and fact-checked by a second reviewer. Study quality was assessed using the U.S. Preventive Services Task Force framework. A meta-analysis on short-term mortality in intensive care unit (ICU) patients was performed using a random-effects model. Strength of the body of evidence was assessed according to the AHRQ Methods Guide.

Results:

There were 18 randomized, controlled trials that addressed five patient populations. Procalcitonin guidance reduces antibiotic use when used to discontinue antibiotics in adult ICU patients and to initiate or discontinue antibiotics in patients with respiratory tract infections (high evidence), without increasing morbidity (moderate evidence) and mortality (low evidence). In contrast, procalcitonin-guided intensification of antibiotics in adult ICU patients increases morbidity (moderate evidence). There is moderate evidence from a single good quality study that procalcitonin guidance reduces antibiotic use for suspected early neonatal sepsis, but insufficient evidence on morbidity and mortality outcomes was found. Evidence is insufficient to draw conclusions on outcomes of procalcitonin guidance for: (1) fever of unknown source in children 1–36 months of age; and (2) preemptive antibiotics after surgery.

Immunocompromised hosts and other special populations were generally excluded from procalcitonin guidance studies. Thus, findings from this review should not be extrapolated to patients with the following conditions: pregnancy; absolute neutropenia; immunocompromised states; chronic infections, and infections for which prolonged antibiotic therapy is standard of care (e.g., infective endocarditis).

Conclusions:

Procalcitonin guidance reduces antibiotic use when used to discontinue antibiotics in adult ICU patients and to initiate or discontinue antibiotics in patients with respiratory tract infections. Populations for future research include immunocompromised patients, patients with other conditions (e.g., pregnancy, cystic fibrosis), and pediatric patients. Future research should compare procalcitonin guidance with antibiotic stewardship programs and to implementation of guidelines. Outcomes of high interest for future research are the consequences of reduction in antibiotic use for antibiotic resistance and for adverse events of antibiotic therapy.