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

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

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 decisionmaking 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. 

Future work: future trials must include an implementation framework to improve trial intervention fidelity, and repeated cycles of education and training to facilitate implementation of biomarker-guided algorithms into routine clinical care.

1366-5278
Waldron, Cherry Ann
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Pallmann, Philip
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Schoenbuchner, Simon
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Harris, Debbie
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Brookes-Howell, Lucy
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Mateus, Céu
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Bernatoniene, Jolanta
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Cathie, Katrina
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Faust, Saul N.
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Henley, Josie
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Hinds, Lucy
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Hood, Kerry
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Huang, Chao
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Jones, Sarah
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Kotecha, Sarah
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Milosevic, Sarah
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Nabwera, Helen
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Patel, Sanjay
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Paulus, Stéphane
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Powell, Colin V.E.
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Preston, Jenny
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Xiang, Huasheng
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Thomas-Jones, Emma
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Carrol, Enitan D.
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Whitbread, Jenny
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Owens, Daniel
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Pond, Jenny
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Cook, Amber
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Oliver, Zoe
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Douglas, Claire
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Jordan, Zoe
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Hawkins, Rachael
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Evans, Judith
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Clarkstone, Sam
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Maboshe, Waku
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Goddard, Mark
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Channon, Sue
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Henley, Josie
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Milosevic, Sarah
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Prout, Hayley
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Smallman, Kim
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et al.
the BATCH trial team
Waldron, Cherry Ann
74f893bb-7b67-4f67-b598-7d598cfd4085
Pallmann, Philip
1ca83b21-3bfd-4905-b055-bb9e8e410c01
Schoenbuchner, Simon
18673c65-6bda-492d-a294-29414b0d1642
Harris, Debbie
60588324-3deb-4ea7-b1b0-4ff40db466db
Brookes-Howell, Lucy
307c5275-082d-4586-ba9d-461527607164
Mateus, Céu
b81ab3dc-7298-46cc-9e20-a9ecaa4db3a5
Bernatoniene, Jolanta
3282aef6-23c2-4e25-bf38-9cb8ea41daea
Cathie, Katrina
ec8dd2eb-0be9-4567-b87d-72eadf5a254b
Faust, Saul N.
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Henley, Josie
04140131-4690-4af9-a616-d731d8b22851
Hinds, Lucy
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Hood, Kerry
79d7555b-fcdd-4fe1-8344-cd9859c7cbed
Huang, Chao
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Jones, Sarah
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Kotecha, Sarah
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Milosevic, Sarah
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Nabwera, Helen
7ea5fb80-f254-4582-8e4e-cfe0809bad8f
Patel, Sanjay
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Paulus, Stéphane
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Powell, Colin V.E.
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Preston, Jenny
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Xiang, Huasheng
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Thomas-Jones, Emma
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Carrol, Enitan D.
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Whitbread, Jenny
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Owens, Daniel
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Pond, Jenny
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Cook, Amber
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Oliver, Zoe
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Douglas, Claire
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Jordan, Zoe
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Hawkins, Rachael
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Evans, Judith
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Clarkstone, Sam
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Maboshe, Waku
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Goddard, Mark
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Channon, Sue
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Henley, Josie
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Milosevic, Sarah
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Prout, Hayley
102656cf-4207-4752-af0c-58e08dfec39b
Smallman, Kim
91b5e722-16b2-4166-9a7d-f78d3c741e46

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 V.E., Preston, Jenny, Xiang, Huasheng, Thomas-Jones, Emma and Carrol, Enitan D. , et al. and the BATCH trial team (2025) 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). (doi:10.3310/MBVA3675).

Record type: Article

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 decisionmaking 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. 

Future work: future trials must include an implementation framework to improve trial intervention fidelity, and repeated cycles of education and training to facilitate implementation of biomarker-guided algorithms into routine clinical care.

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Published date: May 2025

Identifiers

Local EPrints ID: 503305
URI: http://eprints.soton.ac.uk/id/eprint/503305
ISSN: 1366-5278
PURE UUID: b98b4f55-6629-422a-af95-b8302c33d21b
ORCID for Katrina Cathie: ORCID iD orcid.org/0000-0001-5074-0769
ORCID for Saul N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

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Date deposited: 29 Jul 2025 16:32
Last modified: 22 Aug 2025 01:56

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Contributors

Author: Cherry Ann Waldron
Author: Philip Pallmann
Author: Simon Schoenbuchner
Author: Debbie Harris
Author: Lucy Brookes-Howell
Author: Céu Mateus
Author: Jolanta Bernatoniene
Author: Katrina Cathie ORCID iD
Author: Saul N. Faust ORCID iD
Author: Josie Henley
Author: Lucy Hinds
Author: Kerry Hood
Author: Chao Huang
Author: Sarah Jones
Author: Sarah Kotecha
Author: Sarah Milosevic
Author: Helen Nabwera
Author: Sanjay Patel
Author: Stéphane Paulus
Author: Colin V.E. Powell
Author: Jenny Preston
Author: Huasheng Xiang
Author: Emma Thomas-Jones
Author: Enitan D. Carrol
Author: Jenny Whitbread
Author: Daniel Owens
Author: Jenny Pond
Author: Amber Cook
Author: Zoe Oliver
Author: Claire Douglas
Author: Zoe Jordan
Author: Rachael Hawkins
Author: Judith Evans
Author: Sam Clarkstone
Author: Waku Maboshe
Author: Mark Goddard
Author: Sue Channon
Author: Josie Henley
Author: Sarah Milosevic
Author: Hayley Prout
Author: Kim Smallman
Corporate Author: et al.
Corporate Author: the BATCH trial team

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