Microdialysis assessment of gentamicin for second-line antimicrobial prophylaxis in abdominal surgery

INTRODUCTION: Surgical site infections (SSIs) are a leading cause of healthcare-associated infections, particularly in abdominal surgery. In patients allergic to beta-lactams, gentamicin is often used for surgical antibiotic prophylaxis (SAP), but its efficacy is questioned due to limited tissue-level pharmacokinetic/pharmacodynamic (PK/PD) data. MATERIALS AND METHODS: We conducted a monocentric prospective study involving eight adult patients undergoing major abdominal surgery who received gentamicin (5 mg/kg IV) for SAP. Subcutaneous unbound gentamicin concentrations were measured using microdialysis over 6 h. Plasma and tissue PKs were analysed using nonlinear mixed-effects modelling. Monte Carlo simulations assessed the probability of target attainment (PTA) for Cmax/MIC >8 at doses of 5 and 8 mg/kg, using EUCAST MIC distributions for Escherichia coli and Staphylococcus aureus. RESULTS: A total of 246 samples were collected (100 plasma and 146 microdialysate). Subcutaneous gentamicin concentrations were lower than plasma concentrations throughout the 0-6 h interval. Mean Cmax values were 43.7 ± 4.5 mg/L in plasma and 17.8 ± 11.5 mg/L in subcutaneous tissue. Given the lack of defined tissue PK/PD targets in surgical prophylaxis, a plasma-based Cmax/MIC > 8 target was used for PTA simulations. At 5 mg/kg, PTA was suboptimal for MIC ≥1 mg/L in subcutaneous tissue. Simulations showed that increasing the dose to 8 mg/kg improved the cumulative fraction of response against E. coli and S. aureus from 70% and 79% to 80% and 87%, respectively. DISCUSSION: This study highlights insufficient subcutaneous gentamicin exposure with standard SAP dosing. An 8 mg/kg dose improved tissue PK/PD target attainment, supporting updated dosing recommendations for beta-lactam-allergic patients. Further research is needed to validate safety and efficacy in broader populations.