title: Levofloxacin vs. azithromycin pharmacodynamic activity against S. pneumoniae and H. influenzae with decreased susceptibility to amoxicillin/clavulanic acid.
abstract: Resistant clones/phenotypes are putting into question the activity of commonly used beta-lactams, thus prompting the need for alternative options. A 500 mg levofloxacin vs. azithromycin once daily pharmacodynamic simulation was performed against 10(8) cfu/ml of four Streptococcus pneumoniae strains (exhibiting higher amoxicillin than penicillin MIC) and four Haemophilus influenzae strains: beta-lactamase producing, BLNAR (beta-lactamase-negative ampicillin-resistant) and BLPACR (beta-lactamase-positive amoxicillin/clavulanate-resistant). High levofloxacin AUC/MIC values for H. influenzae, and values of 50-100 for S. pneumoniae produced a >5 log(10) reduction at 24h for all strains. Azithromycin AUC/MIC values of approximately 10 were needed to obtain a 2-3 log(10) reduction of S. pneumoniae initial inocula, but lower AUC/MIC values (of approximately 6) obtained > or =3 log(10) reduction against all strains of H. influenzae. While in vitro simulated serum concentrations of levofloxacin were bactericidal at the end of the dosing interval against all S. pneumoniae strains and azithromycin against the susceptible ones, both antimicrobials achieved this endpoint against the BLNAR and BLPACR strains.
authors.affiliation: Microbiology Dept., Universidad Complutense, Madrid, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Alou
authors.forename: L
authors.initials: L
authors.lastname: Aguilar
authors.forename: D
authors.initials: D
authors.lastname: Sevillano
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: J E
authors.initials: JE
authors.lastname: Martín
authors.forename: L
authors.initials: L
authors.lastname: Valdés
authors.forename: J
authors.initials: J
authors.lastname: Prieto
mesh_terms: D000658:Amoxicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents; D017963:Azithromycin / Q000494:pharmacology*; D019818:Clavulanic Acid; D003198:Computer Simulation; D024881:Drug Resistance, Bacterial; D006193:Haemophilus influenzae / Q000187:drug effects*; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D019818:Clavulanic Acid; D064704:Levofloxacin; D000658:Amoxicillin; D017963:Azithromycin; D015242:Ofloxacin