Cidal activity of oral third-generation cephalosporins against Streptococcus pneumoniae in relation to cefotaxime intrinsic activity

This study explores the killing kinetics within 12 h of four oral third-generation cephalosporins against ten Streptococcus pneumoniae strains exhibiting cefotaxime minimum inhibitory concentrations (MICs) from 0.03 to 2 mu g/ml. Killing curves were performed with concentrations achievable in serum after standard doses (0.015-4 mu g/ml). Reductions of 90% were achieved with all compounds at serum-achievable concentrations for strains exhibiting cefotaxime MIC <= 0.5 mu g/ml. Against strains with cefotaxime MIC >= 1 mu g/ml, only cefditoren reached a 90% reduction with concentrations of 0.5-1 mu g/ml doses. At 4 mu g/ml, cefditoren and cefotaxime reached 99.9% reduction in seven of the ten strains studied. At serum-achievable concentrations, cefdinir and cefixime were not bactericidal against strains exhibiting cefotaxime MIC >= 0.25 mu g/ml and >= 0.5 mu g/ml, respectively. Cefditoren showed the best killing kinetic profiles and this observation may be important when choosing an oral third-generation cephalosporin as initial or sequential therapy.