title: Beta-lactam activity against penicillin-resistant Streptococcus pneumoniae strains exhibiting higher amoxicillin versus penicillin minimum inhibitory concentration values: an in vitro pharmacodynamic simulation.
abstract: BACKGROUND
  Activity of simulated serum concentrations after oral therapy with 400 mg cefditoren pivoxil b.i.d., 500 mg cefuroxime axetil b.i.d. and 875/125 mg amoxicillin/clavulanic acid b.i.d. and t.i.d. regimens was explored over 24 h against Streptococcus pneumoniae.
  
  
  METHODS
  Computerized pharmacodynamic simulations were performed against strains with penicillin/amoxicillin/cefuroxime/cefditoren minimum inhibitory concentrations (MICs, microg/ml) and serotypes: strain 1 (0.25/0.12/1/0.12; serotype 6A), strain 2 (2/4/ 2/0.25; serotype 6B), strain 3 (4/16/4/0.5; serotype 14), and strain 4 (4/16/8/1; serotype 14).
  
  
  RESULTS
  Bactericidal activity (> or =3 log(10) reduction) at 12 and 24 h was obtained against all strains with cefditoren, against strains 1 and 2 with cefuroxime and amoxicillin/clavulanic acid t.i.d., but only against strain 1 with amoxicillin/clavulanic acid b.i.d.. Bactericidal activity at 24 h was related to T > MIC of >30% dosing interval, 1.7-2.0 log(10) reductions with T > MIC of 20-30%, and <1 log(10) reduction or regrowth with T > MIC of 0%.
  
  
  CONCLUSIONS
  It is difficult to achieve pharmacodynamic coverage and bactericidal activity by physiological concentrations of oral beta-lactams against penicillin-resistant pneumococcal strains exhibiting higher amoxicillin versus penicillin MICs. Cefditoren may offer alternatives.
authors.affiliation: Microbiology Department, School of Medicine, Complutense University, Madrid, Spain.
authors.forename: D
authors.initials: D
authors.lastname: Sevillano
authors.forename: L
authors.initials: L
authors.lastname: Aguilar
authors.forename: L
authors.initials: L
authors.lastname: Alou
authors.forename: M J
authors.initials: MJ
authors.lastname: Giménez
authors.forename: N
authors.initials: N
authors.lastname: González
authors.forename: O
authors.initials: O
authors.lastname: Echeverría
authors.forename: M
authors.initials: M
authors.lastname: Torrico
authors.forename: L
authors.initials: L
authors.lastname: Valdes
authors.forename: P
authors.initials: P
authors.lastname: Coronel
authors.forename: J
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000502:physiology*; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D010403:Penicillin Resistance / Q000187:drug effects* / Q000502:physiology; D010406:Penicillins / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification / Q000502:physiology; D047090:beta-Lactams / Q000494:pharmacology*
chemical_list: D010406:Penicillins; D047090:beta-Lactams; D000658:Amoxicillin