Sitafloxacin (DU-6859a) and trovafloxacin: Postantibiotic effect and in
vitro interactions with rifampin on methicillin-resistant Staphylococcus
aureus
Sitafloxacin (DU-6859a) and trovafloxacin are novel quinolones potent on
methicillin-resistant Staphylococcus aureus (MRSA) that are designed far
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 offer exposure to
1x and 4x MIC. Rifampin was applied for interactive studies at a
concentration of 2 mu g/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. (C) 1999 Elsevier Science Inc
