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

## TL;DR

This study shows that antibiotics used before and after surgery can change immune cell behavior, especially in CD4+ lymphocytes, which may affect recovery and infection risk.

## Contribution

The study reveals that cefuroxime specifically alters CD4+ lymphocyte immunophenotype ex vivo in high-risk surgical patients.

## Key findings

- Cefuroxime increased IFN-γ and IL-2 in CD4+ lymphocytes at low and high doses.
- Cefuroxime reduced Th2, Th17, and regulatory markers in CD4+ lymphocytes.
- Higher cefuroxime doses altered Th1 cell viability and surface marker expression.

## 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 %Th1 population, with a parallel decrease in %Th2, %Th17, IL-17A, FOX-P3, and T-bet. Among the Th1 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.