Effectiveness of biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: the BATCH RCT

Waldron, Cherry-Ann; Pallmann, Philip; Schoenbuchner, Simon; Harris, Debbie; Brookes-Howell, Lucy; Mateus, Céu; Bernatoniene, Jolanta; Cathie, Katrina; Faust, Saul N; Henley, Josie; Hinds, Lucy; Hood, Kerry; Huang, Chao; Jones, Sarah; Kotecha, Sarah; Milosevic, Sarah; Nabwera, Helen; Patel, Sanjay; Paulus, Stéphane; Powell, Colin VE; Preston, Jenny; Xiang, Huasheng; Thomas-Jones, Emma; Carrol, Enitan D

Abstract

Background
Procalcitonin is a biomarker specific for bacterial infection, with a more rapid response than other commonly used biomarkers, such as C-reactive protein, but it is not routinely used in the National Health Service.

Objective
To determine if using a procalcitonin-guided algorithm may safely reduce duration of antibiotic therapy compared to standard of care in hospitalised children with suspected or confirmed infection.

Design
A pragmatic, multicentre, open-label, parallel two-arm, individually randomised controlled trial with internal pilot phase, qualitative study and health economic evaluations.

Setting
Paediatric wards or paediatric intensive care units within children’s hospitals (n = 6) and district general hospitals (n = 9) in the United Kingdom.

Participants
Children aged between 72 hours and 18 years admitted to hospital and being treated with intravenous antibiotics for suspected or confirmed bacterial infection.

Interventions
Procalcitonin-guided algorithm versus usual standard care alone.

Main outcome measures
Coprimary outcomes were duration of intravenous antibiotic use and a composite safety measure.

Results
Between 11 June 2018 and 12 October 2022, 1949 children were recruited: 977 to the procalcitonin group [427 female (43.7%), 550 male (56.3%)], and 972 to the usual care group [478 female (49.2%), 494 male (50.8%)]. Duration of intravenous antibiotics was not significantly different between the procalcitonin group (median 96.0 hours) and the usual care group (median 99.7 hours) [hazard ratio = 0.96 (0.87, 1.05)], and the procalcitonin-guided algorithm was non-inferior to usual care [risk difference = −0.81% (95% confidence interval upper bound 1.11%)]. At clinical review, a procalcitonin result was available for 81.8% of the time, which was considered as part of clinical decision-making 66.6% of the time, and the algorithm was adhered to 57.2% of the time. Incremental cost-effectiveness ratio per duration of intravenous antibiotics hour avoided from bootstrapped samples was £467.62 per intravenous antibiotic hour avoided. Cost analysis of complete cases was also higher in the procalcitonin arm for all age groups, and for children aged 5 years and over. The intervention is not cost-effective as it is more expensive with no significant improvement in intravenous antibiotic duration.

Limitations
Robust antimicrobial stewardship programmes were already implemented in the lead recruiting sites, and adherence to the algorithm was poor. Clinicians may be reluctant to adhere to biomarker-guided algorithms, due to unfamiliarity with interpreting the test result.

Conclusions
In children hospitalised with confirmed or suspected bacterial infection, the addition of a procalcitonin-guided algorithm to usual care is non-inferior in terms of safety, but does not reduce duration of intravenous antibiotics, and is not cost-effective. In the presence of robust antimicrobial stewardship programmes to reduce antibiotic use, a procalcitonin-guided algorithm may offer little added value.

Citation

Waldron, C.-A., Pallmann, P., Schoenbuchner, S., Harris, D., Brookes-Howell, L., Mateus, C., Bernatoniene, J., Cathie, K., Faust, S. N., Henley, J., Hinds, L., Hood, K., Huang, C., Jones, S., Kotecha, S., Milosevic, S., Nabwera, H., Patel, S., Paulus, S., Powell, C. V., …Carrol, E. D. (in press). Effectiveness of biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: the BATCH RCT. Health Technology Assessment, 29(16), https://doi.org/10.3310/mbva3675

• Journal Article Type: Article
• Acceptance Date: Oct 31, 2024
• Deposit Date: May 20, 2025
• Publicly Available Date: May 21, 2025
• Electronic ISSN: 2046-4924
• Publisher: NIHR Journals Library
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 16
• DOI: https://doi.org/10.3310/mbva3675
• Public URL: https://hull-repository.worktribe.com/output/5179267