Plasma and subcutaneous interstitial fluid vancomycin and gentamicin concentrations in three patients undergoing open...

Patients undergoing open abdominal aortic aneurysm (AAA) repair are at risk of surgical site infections (SSIs). In patients allergic to cefazolin, intravenous vancomycin and gentamicin are commonly recommended for SSI prophylaxis. We aimed to describe unbound vancomycin and gentamicin plasma and subcutaneous interstitial fluid (ISF) concentrations during open AAA repair following intravenous administration given for surgical prophylaxis.

Three patients undergoing open AAA repair surgery were administered a single dose of intravenous vancomycin and gentamicin. Microdialysis catheters were inserted into the subcutis to measure drug concentrations in ISF. Serial plasma and microdialysis samples were collected perioperatively. Non-compartmental pharmacokinetic analysis was performed. Concentrations were compared with a target of 2 mg/L, the epidemiological cut-off value (ECOFF) for vancomycin against Staphylococcus aureus and gentamicin against Escherichia coli.

All patients received 1000 mg vancomycin (infused over 27-57 min) and 3 mg/kg gentamicin (administered over 0.5-5 min). Plasma concentrations of both agents remained >2 mg/L throughout. ISF C_max was >2 mg/L for both drugs in all cases; however, only Subject 1 maintained concentrations >2 mg/L for both agents across the study period. The exposure ratio (unbound ISF AUC_last/unbound plasma AUC_last) was low in two subjects and moderate in one subject, with variability across subjects for both drugs.

Tissue penetration of vancomycin and gentamicin was low to moderate and variable, and target subcutaneous ISF concentrations were not consistently achieved in two cases. Larger pharmacokinetic studies are required to determine optimal dosing.