Getting It Right the Second Time: How Can we Optimize First-Generation Cephalosporin Dosing for Skin and Soft Tissue Infections in the 21st Century?

Optimal cephalexin and cefadroxil dosing for skin and soft tissue infections (SSTIs) is unclear. We summarize clinical and pharmacokinetic/pharmacodynamic (PK/PD) data that compare dosing strategies for SSTIs. Additionally, we conduct population PK target attainment simulations for varying doses of cephalexin and cefadroxil for Staphylococcus aureus and Group A Streptococcus. Although some clinical data support lower doses in mild SSTIs, higher doses optimize PK/PD parameters in moderate-severe SSTIs, especially due to Staphylococcus aureus. Further prospective clinical and PK/PD studies, especially in obese adults, would be beneficial.