title: Influence of penicillin/amoxicillin non-susceptibility on the activity of third-generation cephalosporins against Streptococcus pneumoniae.
abstract: 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 microg/ml of cefditoren and 4 microg/ml of cefixime. Penicillin-intermediate strains were susceptible to cefotaxime and ceftriaxone, with <50% susceptibility to cefdinir and cefpodoxime. The MIC(50) and MIC(90) values of cefditoren were 0.25 microg/ml and 0.5 microg/ml, respectively, whereas cefixime exhibited only marginal activity (MIC(90)=16 microg/ml). Penicillin-resistant strains were resistant to cefdinir and cefpodoxime, with 74.8% and 94.1% susceptibility to cefotaxime and ceftriaxone, respectively. Cefditoren MIC(50)/MIC(90) (0.5/1 microg/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 MIC(50)/MIC(90) (0.5/1 microg/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 (MIC(90)=1 microg/ml for penicillin-resistant and 2 microg/ml for amoxicillin-resistant strains). Cefditoren exhibited one-dilution lower MIC(90) values for these strains, even against those of the most troublesome serotypes.
authors.affiliation: Spanish National Reference Pneumococcal Laboratory, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo Km. 2, 28220, Majadahonda, Madrid, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fenoll
authors.forename: M J
authors.initials: MJ
authors.lastname: Giménez
authors.forename: O
authors.initials: O
authors.lastname: Robledo
authors.forename: L
authors.initials: L
authors.lastname: Aguilar
authors.forename: D
authors.initials: D
authors.lastname: Tarragó
authors.forename: J J
authors.initials: JJ
authors.lastname: Granizo
authors.forename: J E
authors.initials: JE
authors.lastname: Martín-Herrero
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology*; D002439:Cefotaxime / Q000494:pharmacology; D002443:Ceftriaxone / Q000494:pharmacology; D002511:Cephalosporins / Q000494:pharmacology*; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D010406:Penicillins / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000254:growth & development / Q000302:isolation & purification
chemical_list: D002511:Cephalosporins; D010406:Penicillins; D002443:Ceftriaxone; D000658:Amoxicillin; D002439:Cefotaxime