Procalcitonin testing does not reduce the duration of antibiotic treatment in hospitalized pediatric patients.

A pioneering study conducted in the UK by the University of Liverpool has investigated the potential of an extra blood test known as procalcitonin (PCT) to safely reduce the duration children require intravenous (IV) antibiotics during their hospital stay.

Despite promising previous analysis, the study, funded by the National Institute for Health and Care Research (NIHR), found that using the PCT biomarker to guide treatment decisions did not reduce antibiotic duration when compared to usual care.

The study, published today in the Lancet Child & Adolescent Health, is part of the 'Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection' (BATCH) trial. BATCH is a national research trial to tackle antibiotic overuse in hospitalised children and reduce the spread of antimicrobial resistance (AMR).

The excessive use of antibiotics is a major contributor to antimicrobial resistance (AMR), which stands as one of the most significant public health issues globally. Infections from resistant strains of bacteria result in prolonged hospitalizations, elevated healthcare expenses, and a rise in death rates. Children are particularly at risk, making it crucial to adopt more prudent antibiotic practices to safeguard their health for the future.

In this research, which took place in 15 hospitals, almost 2,000 children, ranging from 72 hours to 18 years old and suspected of having bacterial infections, were enrolled.

The study revealed that incorporating the PCT test into standard care did not shorten the length of IV antibiotic treatment. While the test was deemed safe, it proved to be more expensive than traditional approaches, and healthcare teams encountered difficulties in incorporating it into their clinical decision-making.

This research follows a systematic review and cost-effectiveness analysis carried out by NICE in 2015, which assessed the use of PCT testing to inform antibiotic treatment for sepsis. The review suggested that additional studies are needed to thoroughly evaluate the benefits of incorporating PCT algorithms in directing antibiotic therapy for hospitalized adults and children with suspected or confirmed severe bacterial infections.

The findings emphasize that simply implementing new tools such as PCT tests is insufficient. Their successful application demands:

• Robust Antimicrobial Stewardship (AMS) programmes: Many hospitals already use AMS programmes to ensure antibiotics are prescribed responsibly, reducing unnecessary use.
• Training and education for Clinicians: Familiarity with new tests and confidence in interpreting results are crucial for success.
• Implementation research: Future studies should identify barriers and facilitators to implementation to optimise fidelity of the intervention.
• Behaviour Change: Better understanding of the complex interactions influencing whether/how/why clinicians act on information from diagnostic tests to make antibiotic prescribing decisions will improve trial intervention fidelity and facilitate implementation and adoption of tests shown to be effective.

The results highlight the necessity of ongoing investment in AMS initiatives and public health efforts aimed at curbing antibiotic overuse. The researchers point out that while PCT-guided treatment did not demonstrate significant advantages in this study, it may still be beneficial in particular circumstances with additional improvements. As the UK advances its Five-Year Antimicrobial Resistance Strategy, this study offers important perspectives on the difficulties of integrating new diagnostic tests within hospital settings.

Chief investigator the University of Liverpool's Professor Enitan Carrol said: "We are pleased to have completed this large multi-centre trial in hospitalised children. Whilst the study did not demonstrate benefit from the additional procalcitonin test, there is important learning for future biomarker-guided trials in the NHS.

"The BATCH study was a pragmatic trial evaluating if the intervention works under real-world conditions where clinicians do not have to adhere to diagnostic algorithms about antibiotic discontinuation. Adherence to the algorithm was low in our study, and there were challenges in integrating the test into routine clinical workflows. The study highlights the importance of including behavior change and implementation frameworks into pragmatic trial designs."

Dr Emma Thomas-Jones, Principal Research Fellow and Deputy Director of Infection, Inflammation & Immunity Trials at the Cardiff Centre for Trials Research, said: "Research is vital to improving the management of serious bacterial infections, like sepsis. On behalf of the team at the Centre for Trial Research, It has been a pleasure working with Professor Carrol on this important trial, and it is testament to the multi-disciplinary team involved in delivering these results, which will make a real difference, providing clear evidence on the use of procalcitonin as a biomarker in guiding clinical decision making about antibiotic discontinuation in children with serious bacterial infections."

The BATCH trial was carried out by prominent universities and healthcare institutions in the UK, such as the University of Liverpool, Liverpool School of Tropical Medicine, Alder Hey Children's NHS Foundation Trust, the Centre for Trials Research at Cardiff University, University of Southampton, Lancaster University, Sheffield Children's NHS Foundation Trust, Oxford University Hospitals NHS Foundation, Bristol Royal Hospital for Children, University Hospital Southampton NHS Foundation Trust, and Hull York Medical School.

This is the most extensive trial ever conducted to assess the effectiveness of PCT-guided antibiotic therapy in pediatric patients.