Evaluation of the need for dosing adaptations in obese patients for surgical antibiotic prophylaxis: a model-based analysis of cefazolin pharmacokinetics.

Summary

Using tissue microdialysis and population PK/PD modeling across plasma and interstitial fluid, the study found that cefazolin 2 g with redosing at 4 hours achieved pharmacodynamic targets for likely SSI pathogens in both obese and non-obese surgical patients. This regimen outperformed 1 g dosing and was robust whether redosed at 3 or 4 hours, with 2 g/4 h emerging as most suitable.

Key Findings

• Tissue microdialysis and PK/PD modeling compared 1 g vs 2 g cefazolin with 3- or 4-hour redosing.
• Cefazolin 2 g with 4-hour redosing achieved >90% PTA and CFR in plasma and interstitial fluid for common SSI pathogens in both obese and non-obese patients.
• A 2 g/4-hour regimen outperformed 1 g strategies across compartments, supporting unified dosing across BMI strata.

Clinical Implications

Adopt cefazolin 2 g with 4-hour intraoperative redosing as a standard prophylactic regimen irrespective of BMI, especially for longer procedures, to ensure sufficient interstitial target-site exposure.

Limitations

• Exact sample sizes for non-obese comparators not detailed in abstract
• Model-based conclusions require external validation in diverse surgical populations and pathogens

Future Directions

Prospective pragmatic trials comparing SSI outcomes using 2 g/4 h vs alternative regimens across BMI and procedure types; integration with local antibiograms and pathogen MIC distributions.