A major UK clinical trial has revealed that a new biomarker testing protocol for sepsis, spearheaded by researchers at the University of Manchester, can safely reduce the duration of antibiotic treatment compared to current practices. The study, which involved 2,760 adult patients across 41 intensive care units in the UK, found that using a procalcitonin (PCT)-guided protocol resulted in a 10% reduction in antibiotic usage without increasing mortality rates.
The findings, presented at the Critical Care Reviews Meeting and published in JAMA, suggest that this approach could lead to significant cost savings for healthcare systems, limit drug side-effects, reduce overtreatment, and curb the development of antimicrobial resistance.
Study Details and Findings
The randomized controlled trial, conducted between January 2018 and June 2024, compared a PCT protocol with a C-reactive protein (CRP) protocol and standard care. Patients were randomly assigned to one of three groups: a PCT-guided group (918 patients), a CRP-guided group (924 patients), and a standard care group (918 patients). Clinicians received daily standardized written advice on antibiotic discontinuation based on either standard care, PCT levels, or CRP levels. The protocols were designed to conceal laboratory test results from clinical staff to minimize potential bias.
The primary outcome was the total duration of antibiotic use. The results showed that the PCT protocol reduced antibiotic duration by 10% compared to standard care. Importantly, all-cause mortality, a key patient safety measure, remained the same across all three groups. There was no significant difference in antibiotic duration between the standard care and CRP protocol groups.
The Role of Procalcitonin
The decision support system relies on a daily blood test that measures procalcitonin (PCT) levels. PCT is a protein produced in response to bacterial infections. Elevated PCT levels indicate a higher likelihood of bacterial infection and sepsis, while decreasing levels suggest a positive response to treatment. The automated system advises doctors on whether to stop antibiotic treatment based on these PCT levels.
Implications for Sepsis Treatment
Professor Paul Dark, Chief Investigator and Professor of Critical Care at the University of Manchester, emphasized the potential impact of the findings: "This simple protocol, if implemented, could significantly change the way sepsis is treated and safely help to combat antimicrobial overuse and resistance—one of the world’s leading health challenges."
He also highlighted the role of precision medicine in tailoring treatment to individual patient needs: "It is also a powerful illustration of how precision medicine can make a real difference to patient care when treatment is tailored to individual test results of each patient."
Sepsis Burden and Current Challenges
Sepsis is a life-threatening condition that arises when the body's immune system overreacts to an infection, leading to tissue and organ damage. In the UK, approximately 50,000 people die from sepsis each year, with 100,000 hospital admissions. Globally, there are an estimated 49 million cases and 1 million deaths annually.
Early recognition and antibiotic administration are critical in sepsis management. However, determining the optimal duration of antibiotic treatment has been a challenge. Currently, doctors rely on their clinical judgment to decide when to discontinue broad-spectrum antibiotics, which are typically reserved for treating sepsis.
Future Directions
The study's findings are expected to inform future NICE (National Institute for Health and Care Excellence) guidance on antibiotic duration in sepsis. Further research is underway to explore the use of biomarkers in initiating antibiotic therapy for sepsis patients.
