The impact of human albumin on the activity of some anti-staphylococcal agents in an in vitro pharmacokinetics / pharmacodynamics model

Abstract

The emergence of anti-staphylococcal drug resistance has significantly increased, thereby making it difficult to control the life-threatening staphylococcal infections. A validated two-compartment in vitro pharmacokinetics / pharmacody¬namics (PK/PD) model has been used in order to estimate the efficacies of some anti-staphylococcal drugs - namely, vancomycin (maximum concentration or Cmax of 3 and 5 mg/L), teicoplanin (Cmax of 5 and 10 mg/L), and minocycline (Cmax of 2 and 4 mg/L) – against a mixed staphylococcal infection (S. aureus ATCC 25923 and S. epidermidis ATCC 12228), with or without human albumin (2%). The PK profile for each drug was simulated as time-concentration de¬pending on the drug’s half-life. The minimum inhibitory concentration (MIC), the relative optical density for bacterial growth, and the exposure / effect relationship (fAUC0-24/MIC) have also been assessed in this study. Our results revealed that minocycline has the best efficacy over other antibiotics against the assessed isolates (single or mixed). Moreover, the addition of albumin exhibited a negative effect on vancomycin and a positive effect on teicoplanin in both the single and the mixed infections. In conclusion, albumin drew a different antibiotic scenario in response to different pathogens.