title: Sitafloxacin (DU-6859a) and trovafloxacin: postantibiotic effect and in vitro interactions with rifampin on methicillin-resistant Staphylococcus aureus.
abstract: Sitafloxacin (DU-6859a) and trovafloxacin are novel quinolones potent on methicillin-resistant Staphylococcus aureus (MRSA) that are designed for once daily administration. In order to define the adequacy of the above regimen for the therapy of infections by multiple drug-resistant MRSA, their postantibiotic effect (PAE), their bactericidal activity, and their interactions with rifampin were determined on 14 MRSA isolates resistant to both ciprofloxacin and rifampin. PAE was defined after 1-h exposure to 1x, 4x, and 10x MIC and the killing effect after exposure to 1x and 4x MIC. Rifampin was applied for interactive studies at a concentration of 2 micrograms/mL, which is equal to its mean serum level. Median PAEs produced by 1x, 4x, and 10x MIC of sitafloxacin were 1.39, 3.75, and 6.61 h respectively, and by 1x, 4x, and 10x MIC of trovafloxacin 0.87, 2.07, and 2.23 h respectively. PAEs achieved by sitafloxacin were statistically shown to be longer than those achieved by trovafloxacin; PAEs achieved by a concentration of 10x MIC of each quinolone did not differ significantly from those achieved by a concentration of 4x MIC. Both the 4x and 10x MIC concentrations produced a more prolonged PAE than the 1x MIC concentration. A rapid bactericidal activity was expressed over the first 6 h of growth by each quinolone involving 80% of isolates enhanced in some isolates by their interaction with rifampin. The above findings revealed an extended PAE and a rapid killing effect of both sitafloxacin and trovafloxacin on MRSA resistant to ciprofloxacin and to rifampin, thus supporting their once daily administration in the therapy of infections by multiple drug-resistant MRSA. However little in vitro benefit is derived by their interaction with rifampin.
authors.affiliation: First Department of Propaedeutic Medicine, Athens Medical School, Greece.
authors.forename: E J
authors.initials: EJ
authors.lastname: Giamarellou-Bourboulis
authors.forename: H
authors.initials: H
authors.lastname: Sambatakou
authors.forename: P
authors.initials: P
authors.lastname: Grecka
authors.forename: Z
authors.initials: Z
authors.lastname: Chryssouli
authors.forename: H
authors.initials: H
authors.lastname: Giamarellou
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology*; D004347:Drug Interactions; D024841:Fluoroquinolones; D006801:Humans; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development
chemical_list: D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; C080163:trovafloxacin; C076246:sitafloxacin; D012293:Rifampin