In vitro Activity of BAY 12-8039, a New 8-Methoxyquinolone

Abstract

BAY 12-8039 is a new 8-methoxyquinolone with antibacterial activity against gram-positive bacteria which is significantly better than those of sparfloxacin or ciprofloxacin. The minimal inhibitory concentrations (MICs) for 90% of methicillin-susceptible Staphylococcus aureus and Staphylococcus epidermidis were 0.062 and 2 mg/l, respectively. The MIC90S for ciprofloxacin-resistant, methicillin-susceptible and methicillin-resistant S. aureus were 8 mg/l. Against the staphylococcal strains tested sparfloxacin was 2-fold and ciprofloxacin ≥ 10-fold less active. MIC₉₀s for Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus agalactiae were 0.125–0.5 mg/l, irrespective of whether strains with diminished ciprofloxacin susceptibility or ciprofloxacin-susceptible strains were tested. Against the streptococci sparfloxacin was 2- to 4-fold less active. Against gram-negative bacteria BAY 12-8039 is almost as active as ciprofloxacin, except for Pseudomonas aeruginosa. Against Bacteroides fragilis, Bacteroides spp. and Clostridium spp. BAY 12-8039 was as active as metronidazole. The bactericidal activity against S. aureus and S. pneumoniae was in contrast to that of the other quinolones tested, penicillin G, amoxicillin ± clavulanate, cefuroxime and clarithromycin, concentration-dependent. As compared to ciprofloxacin, development of resistance was less pronounced. The spontaneous mutation frequency towards BAY 12-8039 resistance was 2.8 × 10^––8 in Escherichia coli, 7.06 × 10^––8 in S. aureus and < 1.4 x 10^––9 in S. pneumoniae.

Benchmarking the In Vitro Activities of Moxifloxacin and Comparator Agents against Recent Respiratory Isolates from 377 Medical Centers throughout the United States

“…This isolate may have possessed mutations in gyrB and parE which have been implicated previously (21,25) as playing a role in fluoroquinolone resistance, although their role is still debatable (18,27,30). Previous studies have shown moxifloxacin to manifest a low mutation rate of Ͻ1.4 ϫ 10 Ϫ9 at 4 times the MIC, compared with 2.2 ϫ 10 Ϫ7 for ciprofloxacin (10), providing at least circumstantial evidence that the emergence of fluoroquinolone resistance during appropriate moxifloxacin therapy is unlikely. Of course such benefits are negated should the widespread use of less-active compounds with a greater tendency to select for mutations occur, especially since we know that key mutations will have at least some effect on the activity of all quinolones (18) and appear to be stable over time (19).…”

Effect of formulation factors on in vitro permeation of moxifloxacin from aqueous drops through excised goat, sheep, and buffalo corneas

“…This fourth-generation fluoroquinolone has in vitro activity similar to that of ciprofloxacin and ofloxacin against gram-negative bacteria but enhanced activity against gram-positive bacteria including S aureus. [2][3][4] The fourthgeneration fluoroquinolones, gatifloxacin and moxifloxacin, have been reported to have increased susceptibility to S aureus (isolated from clinical cases of keratitis) compared with second-and third-generation fluoroquinolones such as ciprofloxacin, levofloxacin, or ofloxacin. 5 In experimental staphylococcal keratitis model in rabbits, moxifloxacin has demonstrated greater effectiveness than ciprofloxacin or levofloxacin.…”

Activity of moxifloxacin against Bacteroides fragilis and Escherichia coli in an in vitro pharmacokinetic/pharmacodynamic model employing pure and mixed cultures

“…It has an antimicrobial activity against many Gram-positive and Gram-negative aerobic and anaerobic bacteria as well as atypical bacteria such as Chlamydia and Mycoplasma (Dalhoff et al, 1996;Bauernfeind, 1997;Goldstein et al, 1997;Edlund et al, 1998;Ackermann et al, 2000;Blondeau et al, 2000;Kleinkauf et al, 2001;Krasemann et al, 2001;Talan, 2001;Zhanel et al, 2002).…”