Clinical Question

Can the use of procalcitonin levels to determine when to discontinue antibiotic therapy safely reduce the duration of antibiotic use in critically ill patients?

Bottom Line

For patients in the intensive care unit (ICU) who receive antibiotics for presumed or proven bacterial infections, the use of procalcitonin levels to determine when to stop antibiotic therapy results in decreased duration and consumption of antibiotics without increasing mortality. (Level of Evidence = 1b)

Synopsis

To test the effectiveness and safety of procalcitonin-guided antibiotic therapy, these investigators recruited patients in the ICU who had received their first doses of antibiotics for a presumed or proven bacterial infection within 24 hours of enrollment. Patients who were severely immunosuppressed and patients requiring prolonged courses of antibiotics (such as those with endocarditis) were excluded. Using concealed allocation, patients were assigned to procalcitonin-guided treatment (n = 761) or to usual care (n = 785). The usual care group did not have procalcitonin levels drawn. In the procalcitonin group, patients had a procalcitonin level drawn close to the start of antibiotic therapy and daily thereafter until discharge from the ICU or three days after stopping antibiotic use. These levels were provided to the attending physician who could then decide whether to stop giving antibiotics.

Although the study protocol recommended that antibiotics be discontinued if the procalcitonin level had decreased by more than 80% of its peak value or reached a level of 0.5 mcg per L, the ultimate decision to do so was at the discretion of the attending physician. Overall, fewer than one-half the physicians actually discontinued antibiotics within 24 hours of reaching either of these goals. Despite this, the procalcitonin group had decreased number of days of antibiotic treatment (five vs. seven days; between group absolute difference = 1.22; 95% confidence interval [CI], 0.65 to 1.78; P < .0001) and decreased consumption of antibiotics (7.5 vs. 9.3 daily defined doses; between group absolute difference = 2.69; 95% CI, 1.26 to 4.12; P < .0001). Additionally, when examining 28-day mortality rates, the procalcitonin group was noninferior to the standard group, and ultimately had fewer deaths than the standard group (20% vs. 25%; between group absolute difference = 5.4%; 95% CI, 1.2 to 9.5; P = .012). This mortality benefit persisted at one year.

Study design: Randomized controlled trial (nonblinded)

Funding source: Industry

Allocation: Concealed

Setting: Inpatient (ICU only)

Reference: de JongEvan OersJABeishuizenAet alEfficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis2016;16(7):819–827.