Daily monitoring of the blood biomarker procalcitonin (PCT) can pinpoint when to safely stop antibiotics in adults hospitalised for suspected sepsis, reducing the duration of therapy compared with standard care, a large study finds.
It was known that optimising duration of antibiotic therapy helped to reduce overtreatment, limit unwanted effects and preserve antibiotic effectiveness by minimising resistance, a team of UK-based researchers wrote in JAMA.
However, there was currently no agreed optimal duration for antibiotic therapy for sepsis.
Clinicians tended to use clinical judgment on when to cease antibiotics, with evidence remaining uncertain for the efficacy and safety of therapy guided by inflammatory biomarkers, such as PCT or C-reactive protein (CRP).
To close this evidence gap, the National Institute for Health and Care Research (NIHR) commissioned and funded a three-arm, randomised trial across 41 NHS intensive care units, which enrolled 2,760 adult patients requiring critical care for suspected sepsis.
Eligible patients, who had started intravenous antibiotics before study enrolment, were randomly assigned to either a daily PCT-protocol, a daily CRP-protocol or standard care.
Blood was drawn daily from all participants and sent for testing according to the treatment arm, but the results were concealed from the treating clinicians to minimise bias.
Instead, clinicians received daily written advice from their local clinical research team on either standard care or on PCT or CRP biomarker-guided antibiotic discontinuation.
From randomisation to 28 days, the PCT-guided protocol led to a significant reduction in antibiotic duration compared with standard care (mean duration, 10.7 days for standard care versus 9.8 days for PCT; mean difference, 0.88 days).
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%.
‘The duration reduction is in the order of 10% in antibiotic use for sepsis, which could provide significant cost and labour savings, and might also reduce the development of antimicrobial resistance,” the study authors wrote.
No difference was found in antibiotic duration for standard care compared with the daily CRP-guided protocol and the all-cause mortality for CRP compared with standard care was inconclusive.
The researchers from the University of Manchester, Northern Care Alliance NHS Foundation Trust and the Clinical Trials Unit of the University of Warwick’s Medical School also noted that the trial could not provide evidence for biomarker use in initiating antibiotic therapy as participants had commenced treatment before enrolling.
Chief investigator Professor Paul Dark, professor of critical care at the University of Manchester, said the simple protocol could significantly change the way sepsis is treated and combat antibiotic overuse and resistance.
‘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,’ he said.
Professor Dark, who is also an NHS consultant in critical care medicine at Salford Royal, said sepsis had been at the forefront of UK policymaking since a 2013 Health Service Ombudsman report focusing on sepsis patients who were not treated urgently enough.
‘Ever since then, developing better diagnostics and treatment guidance for GPs and hospital clinicians to help them recognise sepsis at an early stage has been a national priority,’ he said.
Figures suggest there are at least 245,000 sepsis cases diagnosed in the UK every year.
Earlier this year, NICE released updated guidance on identifying and managing sepsis in over-16s recommending better targeting of antibiotics for suspected sepsis.
The updates specified that secondary care teams should target antibiotic use as more is learned about a patient’s condition to ensure the right people receive treatment as soon as possible but the medicines are not overused.
