Procalcitonin Guidance Safely Decreases Antibiotic Use in Critically Ill Patients

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.

Reference: De Jong E, Van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016;16(7):819-827.

Design: Randomized controlled trial (nonblinded); LOE: 1b

Setting: Inpatient (ICU only)

Synopsis: To test the efficacy 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 3 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/L, the ultimate decision to do so was at the discretion of the attending physician. Overall, fewer than 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 (5 days vs 7 days; between group absolute difference = 1.22; 95% CI 0.65-1.78; P < .0001) and decreased consumption of antibiotics (7.5 daily defined doses vs 9.3 daily defined doses; between group absolute difference = 2.69; 1.26-4.12; 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%;1.2-9.5; P = .012). This mortality benefit persisted at 1 year.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

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.

Reference: De Jong E, Van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016;16(7):819-827.

Design: Randomized controlled trial (nonblinded); LOE: 1b

Setting: Inpatient (ICU only)

Synopsis: To test the efficacy 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 3 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/L, the ultimate decision to do so was at the discretion of the attending physician. Overall, fewer than 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 (5 days vs 7 days; between group absolute difference = 1.22; 95% CI 0.65-1.78; P < .0001) and decreased consumption of antibiotics (7.5 daily defined doses vs 9.3 daily defined doses; between group absolute difference = 2.69; 1.26-4.12; 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%;1.2-9.5; P = .012). This mortality benefit persisted at 1 year.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.

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.

Reference: De Jong E, Van Oers JA, Beishuizen A, et al. Efficacy and safety of procalcitonin guidance in reducing the duration of antibiotic treatment in critically ill patients: a randomised, controlled, open-label trial. Lancet Infect Dis 2016;16(7):819-827.

Design: Randomized controlled trial (nonblinded); LOE: 1b

Setting: Inpatient (ICU only)

Synopsis: To test the efficacy 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 3 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/L, the ultimate decision to do so was at the discretion of the attending physician. Overall, fewer than 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 (5 days vs 7 days; between group absolute difference = 1.22; 95% CI 0.65-1.78; P < .0001) and decreased consumption of antibiotics (7.5 daily defined doses vs 9.3 daily defined doses; between group absolute difference = 2.69; 1.26-4.12; 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%;1.2-9.5; P = .012). This mortality benefit persisted at 1 year.

Dr. Kulkarni is an assistant professor of hospital medicine at Northwestern University in Chicago.