Pharmacodynamics of Simulated Total Versus Free-Drug Serum Concentrations of A Low Versus A High Protein Bound Third-Generation Oral Cephalosporin (cefpodoxime Versus Cefditoren) Against Streptococcus Pneumoniae

Pharmacodynamic parameters and bactericidal activity against Streptococcus pneumoniae were investigated by simulating total and free serum concentrations of cefpodoxime versus cefditoren. Total drug T>MIC against the penicillin-intermediate (PISP) and resistant (PRSP) strains were 70.6% and 42.9% for cefpodoxime, and 89.6% and 62.5% for cefditoren, respectively. Comparing activity of free versus total cefpodoxime, there were reductions of 8.5% and 19.1% in T>MIC, related to bactericidal activity reductions from approximately 4.5 to 3 log(10), and from 3 to 2.5 log(10) against PISP and PRSP, respectively, at 10-12h. For cefditoren, reductions of 45.4% and 100% in T>MIC, were related to bactericidal activity reductions from approximately 5.5 to 2-2.5 log(10) and from approximately 2.5 to 1.5 log(10) against PISP and PRSP, respectively, at 10-12h. Higher differences in activity were found against the less resistant strains when comparing total versus free-drug profile.