IMPORTANCE: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.
OBJECTIVE: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.
DESIGN, SETTING, AND PARTICIPANTS: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (=18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.
INTERVENTION: From January 1, 2018, to June 5, 2024, 918 patients were assigned to the daily PCT-guided protocol, 924 to the daily CRP-guided protocol, and 918 assigned to standard care.
MAIN OUTCOMES AND MEASURES: The primary outcomes were total duration of antibiotics (effectiveness) and all-cause mortality (safety) to 28 days. Secondary outcomes included critical care unit data and hospital stay data. Ninety-day all-cause mortality was also collected.
RESULTS: Among the randomized patients (mean age 60.2 [SD, 15.4] years; 60.3% males), there was a significant reduction in antibiotic duration from randomization to 28 days for those in the daily PCT-guided protocol compared with standard care (mean duration, 10.7 [SD, 7.6] days for standard care and 9.8 [SD, 7.2] days for PCT; mean difference, 0.88 days; 95% CI, 0.19 to 1.58, P = .01). For all-cause mortality up to 28 days, the daily PCT-guided protocol was noninferior to standard care, where the noninferiority margin was set at 5.4% (19.4% [170 of 878] of patients receiving standard care; 20.9% [184 of 879], PCT; absolute difference, 1.57; 95% CI, -2.18 to 5.32; P = .02). No difference was found in antibiotic duration for standard care vs daily CRP-guided protocol (mean duration, 10.6 [7.7] days for CRP; mean difference, 0.09; 95% CI, -0.60 to 0.79; P = .79). For all-cause mortality, the daily CRP-guided protocol was inconclusive compared with standard care (21.1% [184 of 874] for CRP; absolute difference, 1.69; 95% CI, -2.07 to 5.45; P = .03).
CONCLUSIONS AND RELEVANCE: Care guided by measurement of PCT reduces antibiotic duration safely compared with standard care, but CRP does not. All-cause mortality for CRP was inconclusive.
TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN47473244.
| Discipline Area | Score |
|---|---|
| Hospital Doctor/Hospitalists |  |
| Internal Medicine | |
| Infectious Disease | |
| Intensivist/Critical Care | |
Although significant, the potential management change to detect elevated PCT levels was not clinically relevant and resulted in shortening antibiotic use by less than a day.
This well-designed clinical trial has relevant implications for clinical practice. Although biomarkers had a small effect on individual-patient basis, the public health effect is large since a 10% reduction of broad-spectrum antibiotics can provide a major societal benefit in terms of less antibiotic exposure, less antibiotic-induced side effects, less development of antibiotic resistance, and decreased public cost. Also new from this study is that procalcitonin consistently performed better than CRP to de-escalate antibiotics.
This large UK multicenter trial demonstrates that monitoring procalcitonin may reduce the amount and duration of antibiotics administered in patients with sepsis. The decrease was modest and also relied on recommendations from the study team. Will need further study to see whether this is a reliable marker.
High-quality trial showing a 10% reduction in antibiotic days with procalcitonin-guided antibiotic therapy in sepsis / critical care. This was safe. In actual practice, the cost of the additional antibiotics needs to be compared with the economic costs of daily procalcitonin measurement - no data on the assay itself is provided in the main manuscript. I appreciate that PCT can be an additional data point and look forward to having more biomarkers move their way to routine practice.
