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 1×, 4×, and 10× MIC and the killing effect after exposure to 1× and 4× MIC. Rifampin was applied for interactive studies at a concentration of 2 μg/mL, which is equal to its mean serum level. Median PAEs produced by 1×, 4×, and 10× MIC of sitafloxacin were 1.39, 3.75, and 6.61 h respectively, and by 1×, 4×, and 10× 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 10× MIC of each quinolone did not differ significantly from those achieved by a concentration of 4× MIC. Both the 4× and 10× MIC concentrations produced a more prolonged PAE than the 1× 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.