Influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins against Streptococcus pneumoniae

To study the influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins, 430 consecutive penicillin non-susceptible Streptococcus pneumoniae 2007 isolates received in the Spanish Reference Pneumococcal Laboratory were tested. For comparative purposes, 625 penicillin-susceptible 2007 isolates were also tested. Susceptibility was determined by agar dilution using Mueller-Hinton agar supplemented with 5% sheep blood. Penicillin-susceptible strains were susceptible to amoxicillin, cefotaxime and ceftriaxone, 99.8% to cefpodoxime and 99.5% to cefdinir, and were inhibited by 0.12 mu g/ml of cefditoren and 4 mu g/ml of cefixime. Penicillin-intermediate strains were susceptible to cefotaxime and ceftriaxone, with < 50% susceptibility to cefdinir and cefpodoxime. The MIC50 and MIC90 values of cefditoren were 0.25 mu g/ml and 0.5 mu g/ml, respectively, whereas cefixime exhibited only marginal activity (MIC90=16 mu g/ml). Penicillin-resistant strains were resistant to cefdinir and cefpodoxime, with 74.8% and 94.1% susceptibility to cefotaxime and ceftriaxone, respectively. Cefditoren MIC50/MIC90 (0.5/1 mu g/ml) were lower than cefotaxime and ceftriaxone. Among amoxicillin non-susceptible strains, susceptibility to cefdinir and cefpodoxime was < 10%, and susceptibility to cefotaxime decreased from 87.9% in the intermediate category to 63.0% in the resistant group. Cefditoren MIC50/MIC90 (0.5/1 mu g/ml) were lower than cefotaxime. In conclusion, the activity of cefixime, cefdinir and cefpodoxime was highly affected by penicillin/amoxicillin non-susceptibility, while parenteral third-generation cephalosporins exhibited higher intrinsic activity (MIC90=1 mu g/ml for penicillin-resistant and 2 mu g/ml for amoxicillin-resistant strains). Cefditoren exhibited one-dilution lower MIC90 values for these strains, even against those of the most troublesome serotypes.