In vitro activity of amifloxacin against outer membrane mutants of the family Enterobacteriaceae and frequency of spontaneous resistance

Abstract

Amifloxacin showed potent inhibitory activity against DNA gyrase of Escherichia coli. The difference in the susceptibilities of lipopolysaccharide-deficient Salmonella typhimurium mutants and their parent strain was less than twofold, and the difference in the susceptibilities of porin-deficient E. coli mutants and their parent strain was less than twofold. There was cross resistance among the quinolone group of agents; however, the decrease in MIC for norB mutants was slightly lower than that of other fluoroquinolones. Cell lysis was induced with combined treatment of amifloxacin and sodium dodecyl sulfate in E. coli. The frequency of mutants spontaneously resistant to amifloxacin was extremely low in all species tested.

In vitro antibacterial activities of tosufloxacin against and uptake of tosufloxacin by outer membrane mutants of Escherichia coli, Proteus mirabilis, and Salmonella typhimurium

“…The outer membrane permeation of tosufloxacin was more affected by the barrier of LPS than we predicted from its hydrophobicity. Similarly, it has been previously noted that the activity of amifloxacin, which is more hydrophobic than nalidixic acid, was affected little by alterations in the LPS structure (26). These findings together with our results suggest that the permeation of quinolones through a barrier of LPS, at least in part, is not limited simply by the apparent hydrophobicity of the molecules but also by the differences in basal structure (quinoline, naphthyridine, or benzoxazine nucleus) or in each specific moiety.…”

“…One of the major resistance mechanisms is alteration of the subunit structure of DNA gyrase (1,5,10,12,14,16,20,22,27,28,30,31), and another is decreased permeability through the outer membrane from a reduced number of porins (3, 4, 6-8, 11, 13-15). In E. coli, fluoroquinolones are thought to cross the outer membrane primarily through the OmpF porin; this has been demonstrated previously with defined porin-deficient strains (4,6,13,26). Moreover, the lipopolysaccharide (LPS)-deficient (rough) mutants were more susceptible to hydrophobic quinolones than was the wild-type strain, suggesting that the passage of quinolones through the outer membrane is not limited to porins (13).…”

Transferable imipenem resistance in Pseudomonas aeruginosa

“…Antibacterial susceptibility was measured by an agar dilution method using sensitivity disk agar (Nissui, Tokyo, Japan) (24).…”

Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples

“…Indeed, amifloxacin, a larger fraction of which exists in the uncharged form (Fig. 3A), appears to diffuse more significantly through the OM bilayer in comparison with norfloxacin (46). Another case involves mycobacteria, whose cell wall lipids constitute a very effective permeation barrier (25).…”