Peri-Operative Antimicrobial Prophylaxis Modulates CD4+ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study

Paketci, Susi; Williams, Jack; Pisciotta, Walter; Loye, Richard; Waller, Alessia V.; Haque, Rahila; Brealey, David; Singer, Mervyn; Whittle, John; Moonesinghe, Ramani; Arulkumaran, Nishkantha; Snow, Timothy Arthur Chandos; the University College London Hospitals Critical Care Research Team,

doi:10.3390/antibiotics14101026

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Peri-Operative Antimicrobial Prophylaxis Modulates CD4⁺ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study

by

Susi Paketci

^1,†

,

Jack Williams

^1,†,

Walter Pisciotta

¹

,

Richard Loye

¹,

Alessia V. Waller

¹

,

Rahila Haque

¹,

David Brealey

^1,2

,

Mervyn Singer

¹

,

John Whittle

³

,

Ramani Moonesinghe

^2,3

,

Nishkantha Arulkumaran

^1,‡

,

Timothy Arthur Chandos Snow

^1,3,*,‡

and

the University College London Hospitals Critical Care Research Team

^§

¹

Bloomsbury Institute for Intensive Care Medicine, University College London, London WC1E 6BT, UK

²

NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London NW1 2BU, UK

³

Centre for Anaesthesia, Critical Care & Pain Medicine, University College London, London WC1E 6BT, UK

^*

Author to whom correspondence should be addressed.

^†

Joint First author.

^‡

Joint Senior author.

^§

University College London Hospitals Critical Care Research Team: Naveed Saleem, Antonio Cesar, Francis Ryckaert, Deborah Smyth, Georgia Bercades, Ingrid Hass, Alexandra Zapata Martinez, Laura Gallagher, and Gladys Martir.

Antibiotics 2025, 14(10), 1026; https://doi.org/10.3390/antibiotics14101026

Submission received: 29 August 2025 / Revised: 8 October 2025 / Accepted: 10 October 2025 / Published: 14 October 2025

(This article belongs to the Special Issue Antimicrobial Stewardship in Surgical Infection)

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Abstract

Background: Post-operative infections are a significant cause of morbidity in patients undergoing major elective surgery. Peri-operative antibiotics are used to reduce the risk of infection. Several antibiotics modulate the host immune response. Objectives: Our objective was to determine the ex vivo immunomodulatory properties of commonly used antibiotics (amoxicillin, cefuroxime, metronidazole, or combined cefuroxime–metronidazole) on monocyte and lymphocyte phenotypes in patients undergoing major elective surgery. Methods: We performed a prospective cohort study of patients aged ≥18 years admitted to the post-anaesthetic care unit following major elective non-cardiac surgery. Peripheral blood mononuclear cells isolated immediately after surgery were incubated with antibiotics with or without a monocyte (heat-killed E coli) or lymphocyte (CD3/CD28 beads) stimulus ex vivo. Immune cell phenotype was characterised using flow cytometry. Results: Twenty-eight patients were included. All antibiotics tested were associated with a reduction in T-cell viability, and changes to monocytes were minimal. Among CD4⁺ and CD8⁺ lymphocytes, cefuroxime increased IFN-γ (at low and high doses) and increased CD4⁺ lymphocyte IL-2 and IL-2R at higher doses. Among CD4⁺ lymphocytes, at both doses, cefuroxime increased %T_h1 population, with a parallel decrease in %T_h2, %T_h17, IL-17A, FOX-P3, and T-bet. Among the T_h1 sub-population, changes were seen at higher cefuroxime doses, including increased viability and PD-1, and a decrease in FAS, IFN-γ and CD28, and IL-7R expression. Conclusions: The choice of antibiotics directly impacts immune function following major surgery, with cefuroxime associated with ex vivo immunomodulatory effects on CD4⁺ lymphocytes. The functional implications on the development of subsequent post-operative infectious complications and long-term cancer-free survival require further investigation.

Keywords: anti-bacterial agents; beta-lactams; general surgery; immune function; intensive care unit; lymphocyte; monocyte; post-anaesthetic care unit; post-operative infection

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MDPI and ACS Style

Paketci, S.; Williams, J.; Pisciotta, W.; Loye, R.; Waller, A.V.; Haque, R.; Brealey, D.; Singer, M.; Whittle, J.; Moonesinghe, R.; et al. Peri-Operative Antimicrobial Prophylaxis Modulates CD4⁺ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study. Antibiotics 2025, 14, 1026. https://doi.org/10.3390/antibiotics14101026

AMA Style

Paketci S, Williams J, Pisciotta W, Loye R, Waller AV, Haque R, Brealey D, Singer M, Whittle J, Moonesinghe R, et al. Peri-Operative Antimicrobial Prophylaxis Modulates CD4⁺ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study. Antibiotics. 2025; 14(10):1026. https://doi.org/10.3390/antibiotics14101026

Chicago/Turabian Style

Paketci, Susi, Jack Williams, Walter Pisciotta, Richard Loye, Alessia V. Waller, Rahila Haque, David Brealey, Mervyn Singer, John Whittle, Ramani Moonesinghe, and et al. 2025. "Peri-Operative Antimicrobial Prophylaxis Modulates CD4⁺ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study" Antibiotics 14, no. 10: 1026. https://doi.org/10.3390/antibiotics14101026

APA Style

Paketci, S., Williams, J., Pisciotta, W., Loye, R., Waller, A. V., Haque, R., Brealey, D., Singer, M., Whittle, J., Moonesinghe, R., Arulkumaran, N., Snow, T. A. C., & the University College London Hospitals Critical Care Research Team. (2025). Peri-Operative Antimicrobial Prophylaxis Modulates CD4⁺ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study. Antibiotics, 14(10), 1026. https://doi.org/10.3390/antibiotics14101026

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Peri-Operative Antimicrobial Prophylaxis Modulates CD4⁺ Lymphocyte Immunophenotype Ex Vivo in High-Risk Patients Undergoing Major Elective Surgery—A Preliminary Observational Study

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