- Waldron C, Pallmann P, Schoenbuchner S, Harris D, Brookes-Howell L, Mateus C, et al. Effectiveness of biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: the BATCH RCT. Health Technol Assess 2024;29:1–125. 10.3310/MBVA3675
- Waldron CA, Thomas-Jones E, Bernatoniene J, Brookes-Howell L, Faust SN, Harris D, et al. Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection (BATCH): protocol for a randomised controlled trial. BMJ Open 2022;12:e047490. 10.1136/bmjopen-2020-047490
- Marshall JC. Why have clinical trials in sepsis failed? Trends Mol Med 2014;20:195–203. 10.1016/j.molmed.2014.01.00724581450
- Zijlstra JG, van Meurs M, Moser J. Commentary: precision immunotherapy for sepsis. Front Immunol 2019;10:20. 10.3389/fimmu.2019.0002030766529
- Holm H, Nägga K, Nilsson ED, Ricci F, Melander O, Hansson O, et al. Biomarkers of microvascular endothelial dysfunction predict incident dementia: a population-based prospective study. J Intern Med 2017;282:94–101. 10.1111/joim.1262128407377
- Bermejo-Martin J, Martín-Fernandez M, López-Mestanza C, Duque P, Almansa R. Shared features of endothelial dysfunction between sepsis and its preceding risk factors (aging and chronic disease). J Clin Med 2018;7:400. 10.3390/jcm711040030380785
- Lenihan RAF, Ang J, Pallmann P, Romaine ST, Waldron CA, Thomas-Jones E, et al. Mid-regional pro-adrenomedullin in combination with pediatric early warning scores for risk stratification of febrile children presenting to the emergency department: secondary analysis of a nonprespecified United Kingdom Cohort Study. Pediatr Crit Care Med 2022;23:980–9. 10.1097/PCC.000000000000307536239515
- Falschlehner C, Schaefer U, Walczak H. Following TRAIL’s path in the immune system. Immunology 2009;127:145–54. 10.1111/j.1365-2567.2009.03058.x19476510
- Panisova E, Unger WWJ, Berger C, Meyer Sauteur PM. Mycoplasma pneumoniae-specific IFN-gamma-producing CD4(+) effector-memory T cells correlate with pulmonary disease. Am J Respir Cell Mol Biol 2021;64:143–6. 10.1165/rcmb.2020-0237LE33385212
- Hansbro PM, Starkey MR, Mattes J, Horvat JC. Pulmonary immunity during respiratory infections in early life and the development of severe asthma. Ann Am Thorac Soc 2014;11:S297–302. 10.1513/AnnalsATS.201402-086AW25525736
- Oved K, Eden E, Gottlieb TM. Unlocking the power of the host response to improve the management of infectious diseases. Future Microbiol 2019;14:1257–9. 10.2217/fmb-2019-017031849234
- Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 2016;315:801–10. 10.1001/jama.2016.028726903338
- Fischer JE, Ramser M, Fanconi S. Use of antibiotics in pediatric intensive care and potential savings. Intensive Care Med 2000;26:959–66. 10.1007/s00134005128810990113
- Goldmann DA, Weinstein RA, Wenzel RP, Tablan OC, Duma RJ, Gaynes RP, et al. Strategies to prevent and control the emergence and spread of antimicrobial-resistant microorganisms in hospitals. A challenge to hospital leadership. JAMA 1996;275:234–40. 10.1001/jama.1996.035302700740358604178
- Carrol ED, Thomson APJ, Hart CA. Procalcitonin as a marker of sepsis. Int J Antimicrob Agents 2002;20:1–9. 10.1016/s0924-8579(02)00047-x12127705
- Waldron CA, Pallmann P, Schoenbuchner S, Harris D, Brookes-Howell L, Mateus C, et al. Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two arm, individually randomised controlled trial. Lancet Child Adolesc Health 2025;9:121–30. 10.1016/s2352-4642(24)00306-739798581
- McMullan BJ, Andresen D, Blyth CC, Avent ML, Bowen AC, Britton PN, et al.; ANZPID-ASAP group. Antibiotic duration and timing of the switch from intravenous to oral route for bacterial infections in children: systematic review and guidelines. Lancet Infect Dis 2016;16:e139–52. 10.1016/S1473-3099(16)30024-X27321363
- Rello J, van Engelen T, Alp E, Calandra T, Cattoir V, Kern W, et al. Towards precision medicine in sepsis: a position paper from the European Society of Clinical Microbiology and Infectious Diseases. Clin Microbiol Infect 2018;24:1264–72. 10.1016/j.cmi.2018.03.01129581049
- Christaki E, Giamarellos-Bourboulis E. The beginning of personalized medicine in sepsis: small steps to a bright future. Clin Genet 2014;86:56–61. 10.1111/cge.1236824579691
- McGalliard R, Carrol E. A new horizon for sepsis: personalised medicine: hype or hope? Eur J Mol Clin Med 2017;3:289–93. 10.1016/j.nhtm.2017.06.002
- Zhang Z, Zhang G, Goyal H, Mo L, Hong Y. Identification of subclasses of sepsis that showed different clinical outcomes and responses to amount of fluid resuscitation: a latent profile analysis. Crit Care 2018;22:347. 10.1186/s13054-018-2279-330563548
- Seymour CW, Kennedy JN, Wang S, Chang CH, Elliott CF, Xu Z, et al. Derivation, validation, and potential treatment implications of novel clinical phenotypes for sepsis. JAMA 2019;321:2003–17. 10.1001/jama.2019.579131104070
- Levin M, Cunnington AJ, Wilson C, Nadel S, Lang HJ, Ninis N, et al. Effects of saline or albumin fluid bolus in resuscitation: evidence from re-analysis of the FEAST trial. Lancet Respir Med 2019;7:581–93. 10.1016/S2213-2600(19)30114-631196803
- Valenzuela-Sanchez F, Valenzuela-Mendez B, Rodriguez-Gutierrez JF, Estella-Garcia A, Gonzalez-Garcia MA. New role of biomarkers: mid-regional pro-adrenomedullin, the biomarker of organ failure. Ann Transl Med 2016;4:329. 10.21037/atm.2016.08.6527713887
- Saeed K, Wilson DC, Bloos F, Schuetz P, van der Does Y, Melander O, et al. The early identification of disease progression in patients with suspected infection presenting to the emergency department: a multi-centre derivation and validation study. Crit Care 2019;23:255. 10.1186/s13054-019-2329-531307526
- Andaluz-Ojeda D, Cicuendez R, Calvo D, Largo E, Nogales L, Munoz MF, et al. Sustained value of proadrenomedullin as mortality predictor in severe sepsis. J Infect 2015;71:136–9. 10.1016/j.jinf.2015.02.00225704281
- Albrich WC, Ruegger K, Dusemund F, Schuetz P, Arici B, Litke A, et al. Biomarker-enhanced triage in respiratory infections: a proof-of-concept feasibility trial. Eur Respir J 2013;42:1064–75. 10.1183/09031936.0011361223349444
- Hartmann O, Schuetz P, Albrich WC, Anker SD, Mueller B, Schmidt T. Time-dependent Cox regression: serial measurement of the cardiovascular biomarker proadrenomedullin improves survival prediction in patients with lower respiratory tract infection. Int J Cardiol 2012;161:166–73. 10.1016/j.ijcard.2012.09.01423017815
- Elke G, Bloos F, Wilson DC, Brunkhorst FM, Briegel J, Reinhart K, et al.; SepNet Critical Care Trials Group. The use of mid-regional proadrenomedullin to identify disease severity and treatment response to sepsis – a secondary analysis of a large randomised controlled trial. Crit Care 2018;22:79. 10.1186/s13054-018-2001-529562917
- Oved K, Cohen A, Boico O, Navon R, Friedman T, Etshtein L, et al. A novel host-proteome signature for distinguishing between acute bacterial and viral infections. PLOS ONE 2015;10:e0120012. 10.1371/journal.pone.012001225785720
- Lei J, Yin X, Shang H, Jiang Y. IP-10 is highly involved in HIV infection. Cytokine 2019;115:97–103. 10.1016/j.cyto.2018.11.01830472104
- Kaur US, Shet A, Rajnala N, Gopalan BP, Moar PDH, Singh BP, et al. High Abundance of genus Prevotella in the gut of perinatally HIV-infected children is associated with IP-10 levels despite therapy. Sci Rep 2018;8:17679. 10.1038/s41598-018-35877-430518941
- Liu M, Guo S, Hibbert JM, Jain V, Singh N, Wilson NO, Stiles JK. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine Growth Factor Rev 2011;22:121–30. 10.1016/j.cytogfr.2011.06.00121802343
- Ashkenazi-Hoffnung L, Oved K, Navon R, Friedman T, Boico O, Paz M, et al. A host-protein signature is superior to other biomarkers for differentiating between bacterial and viral disease in patients with respiratory infection and fever without source: a prospective observational study. Eur J Clin Microbiol Infect Dis 2018;37:1361–71. 10.1007/s10096-018-3261-329700762
- van Houten CB, de Groot JAH, Klein A, Srugo I, Chistyakov I, de Waal W, et al. A host-protein based assay to differentiate between bacterial and viral infections in preschool children (OPPORTUNITY): a double-blind, multicentre, validation study. Lancet Infect Dis 2017;17:431–40.28012942
- Srugo I, Klein A, Stein M, Golan-Shany O, Kerem N, Chistyakov I, et al. Validation of a novel assay to distinguish bacterial and viral infections. Pediatrics 2017;140:e20163453. 10.1542/peds.2016-345328904072
- Martinon-Torres F, Salas A, Rivero-Calle I, Cebey-Lopez M, Pardo-Seco J, Herberg JA, et al.; EUCLIDS Consortium. Life-threatening infections in children in Europe (the EUCLIDS Project): a prospective cohort study. Lancet Child Adolesc Health 2018;2:404–14. 10.1016/S2352-4642(18)30113-530169282
- Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med 2015;372:793–5. 10.1056/NEJMp150052325635347
- Gallagher R, Kirkham JJ, Mason JR, Bird KA, Williamson PR, Nunn AJ, et al. Development and inter-rater reliability of the Liverpool adverse drug reaction causality assessment tool. PLOS ONE 2011;6:e28096. 10.1371/journal.pone.002809622194808
- National Institute for Health and Care Excellence. Meningitis (bacterial) and meningococcal disease: recognition, diagnosis and management (NG240), 19 March 2024. URL: www.nice.org.uk/guidance/ng240/chapter/Finding-more-information-and-committee-details (accessed 17 December 2025).
- Harwood R, Allin B, Jones CE, Whittaker E, Ramnarayan P, Ramanan AV, et al.; PIMS-TS National Consensus Management Study Group. A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process. Lancet Child Adolesc Health 2021;5:133–41. 10.1016/S2352-4642(20)30304-732956615
- Peterson B, George SL. Sample size requirements and length of study for testing interaction in a 2 x k factorial design when time-to-failure is the outcome [corrected]. Control Clin Trials 1993;14:511–22. 10.1016/0197-2456(93)90031-88119066
- Bello S, Lasierra AB, Mincholé E, Fandos S, Ruiz MA, Vera E, et al. Prognostic power of proadrenomedullin in community-acquired pneumonia is independent of aetiology. Eur Respir J 2012;39:1144–55. 10.1183/09031936.0008041122075489
- Benjamini Y, Yekutieli D. The control of the false discovery rate in multiple testing under dependency. Ann Stat 2001;29:1165–88. 10.1214/aos/1013699998
- Schoenbuchner SM, Huang C, Waldron CA, Thomas-Jones E, Hood K, Carrol ED, Pallmann P. Biomarker-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection: statistical analysis plan for the BATCH trial and PRECISE sub-study. Trials 2023;24:364. 10.1186/s13063-022-06956-937254156
- Gonzalez del Castillo J, Clemente-Callejo C, Llopis F, Irimia A, Oltra-Hostalet F, Rechner C, et al.; INFURG-SEMES investigators. Midregional proadrenomedullin safely reduces hospitalization in a low severity cohort with infections in the ED: a randomized controlled multi-centre interventional pilot study. Eur J Intern Med 2021;88:104–13. 10.1016/j.ejim.2021.03.04133906810
- Basar C, Visneci EF, Osman K, Fatma C, Tuncar A, Taslidere B. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis. Open Med 2023;18:20230865. 10.1515/med-2023-0865
- Indirli R, Bandera A, Valenti L, Ceriotti F, Di Modugno A, Tettamanti M, et al.; COVID-19 Network Working Group. Prognostic value of copeptin and mid-regional proadrenomedullin in COVID-19-hospitalized patients. Eur J Clin Invest 2022;52:e13753. 10.1111/eci.1375335128648
- Salem SS, Saleh NY, Soliman SE, Abo-Haded HM. On-admission plasma levels of BNP, MR-proADM, and cTnI in pediatric heart failure: contributions to diagnosis, prognosis, and outcome. Ir J Med Sci 2022;191:263–70. 10.1007/s11845-021-02533-233564973
- Duijkers R, Prins HJ, Kross M, Snijders D, van den Berg JWK, Werkman GM, et al. Biomarker guided antibiotic stewardship in community acquired pneumonia: a randomized controlled trial. PLOS ONE 2024;19:e0307193. 10.1371/journal.pone.030719339163362
- Srinivasan P, Meena JP, Gupta AK, Halder A, Kapil A, Pandey RM, Seth R. Safety of procalcitonin guided early discontinuation of antibiotic therapy among children receiving cancer chemotherapy and having low-risk febrile neutropenia: a randomized feasibility trial (ProFenC study). Pediatr Hematol Oncol 2024;41:89–102. 10.1080/08880018.2023.224994037655541
- Kubo K, Sakuraya M, Sugimoto H, Takahashi N, Kano KI, Yoshimura J, et al. Benefits and harms of procalcitonin- or C-reactive protein-guided antimicrobial discontinuation in critically ill adults with sepsis: a systematic review and network meta-analysis. Crit Care Med 2024;52:e522–34. 10.1097/ccm.000000000000636638949476
- van Bussel BCT, Ferreira I, van de Waarenburg MPH, van Greevenbroek MMJ, van der Kallen CJH, Henry RMA, et al. Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform. table 1. PLOS ONE 2013;8:e58576. 10.1371/journal.pone.0058576.t00123472208
- Turner R, Hart J, Ashiru-Oredope D, Atkins L, Eades C, Felton T, et al. A qualitative interview study applying the COM-B model to explore how hospital-based trainers implement antimicrobial stewardship education and training in UK hospital-based care. BMC Health Serv Res 2023;23:770. 10.1186/s12913-023-09559-537468860
- Naseem R, Howe N, Pretorius S, Williams C, Lendrem C, Pallmann P, Carrol ED; PROTECT study team. Mapping decision-making pathways: determination of intervention entry points for diagnostic tests in suspected serious infection. NIHR Open Res 2024;4:35. 10.3310/nihropenres.13568.139850633
- Love SB, Cafferty F, Snowdon C, Carty K, Savage J, Pallmann P, et al. Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units. Trials 2022;23:757. 10.1186/s13063-022-06680-436068599
MR-Pro-adrenomedullin (MR-proADM) and Host Immune Response Biomarkers Evaluation of procalcitonin-guided antibiotic duration in Children with Infection for Stratification of Effectiveness: the PRECISE Study · References
References
Attribution. Cherry-Ann Waldron; Philip Pallmann; Simon Schoenbuchner; Debbie Harris; Jolanta Bernatoniene; Katrina Cathie et al. (2026). MR-Pro-adrenomedullin (MR-proADM) and Host Immune Response Biomarkers Evaluation of procalcitonin-guided antibiotic duration in Children with Infection for Stratification of Effectiveness: the PRECISE Study. National Institute for Health and Care Research. Copyright © 2026 Waldron et al. Licensed under CC BY 4.0. NCBI Bookshelf NBK621507. CC BY 4.0. Original source ↗. Text reproduced from the Bookshelf XML without changing wording; figures, images and supplements are not reproduced.