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

Area of Science:

• Pharmacology
• Infectious Diseases
• Surgical Oncology

Background:

• Surgical site infections (SSIs) are a significant complication, especially in abdominal surgery.
• Gentamicin is an alternative antibiotic prophylaxis (SAP) for beta-lactam-allergic patients, but its efficacy is debated due to limited tissue-level data.
• Understanding gentamicin's pharmacokinetic/pharmacodynamic (PK/PM) profile in subcutaneous tissue is crucial for optimizing SAP.

Purpose of the Study:

• To evaluate subcutaneous gentamicin concentrations and pharmacokinetic/pharmacodynamic (PK/PD) target attainment in patients undergoing major abdominal surgery.
• To compare the efficacy of standard 5 mg/kg versus an increased 8 mg/kg gentamicin dose for surgical antibiotic prophylaxis (SAP).

Main Methods:

• A prospective study measured subcutaneous unbound gentamicin concentrations via microdialysis in 8 adult patients over 6 hours.
• Plasma and tissue PK data were analyzed using nonlinear mixed-effects modeling.
• Monte Carlo simulations assessed the probability of target attainment (PTA) for Cmax/MIC >8 at 5 and 8 mg/kg doses against E. coli and S. aureus.

Main Results:

• Subcutaneous gentamicin concentrations were consistently lower than plasma concentrations.
• The standard 5 mg/kg dose showed suboptimal PTA for relevant minimum inhibitory concentrations (MICs) in subcutaneous tissue.
• Increasing the gentamicin dose to 8 mg/kg improved the cumulative fraction of response against E. coli and S. aureus.

Conclusions:

• Standard gentamicin dosing (5 mg/kg) for SAP provides insufficient subcutaneous exposure.
• An 8 mg/kg gentamicin dose enhances tissue PK/PD target attainment, suggesting a revised dosing strategy for beta-lactam-allergic patients.
• Further research is warranted to confirm the safety and efficacy of higher gentamicin doses in diverse patient populations.