Active substances: Norfloxacin
The OqxAB- and QepA-proteins confer resistance to hydrophilic fluoroquinolones like norfloxacin, ciprofloxacin, and enrofloxacin, causing a 32- to 64-fold increase in MICs.
QepA extrudes in addition to quinolones a narrow range of agents such as erythromycin, ethidium bromide, and acrifliavine; OqxAB exports a wider range of agents like ethidium bromide, tetracyclines, chloramphenicol, trimethoprim, olaquindox, and the desinfectants like triclosan.
Extrusion of chemically unrelated agents by efflux-pumps represents a third mechanism of cross-resistance. In conclusion, fluoroquinolone resistance can emerge even in the absence of exposure to this drug class as several coselection mechanisms favour the emergence of quinolone resistance.
Additional Resistance Mechanisms Any antibacterial agent interacting with an intracellular target must traverse the bacterial cell-wall and cytoplasmic membrane to reach the target. Once taken up, most antibacterials are actively effluxed.
Therefore, fluoroquinolones, too, are affected by permeation barriers and efflux pumps, either in association with target modifications or on their own.
As mentioned above, many Gram-positive and Gram-negative fluoroquinolone-resistant mutant strains do not show any mutation in the quinolones resistance determining region QRDR.
Furthermore, chemically unrelated substances like cyclohexane, salicylate, and tetracycline affected fluoroquinolone susceptibilities of E.
Multiple antibiotic resistance mar genes cause an efflux of a variety of chemically unrelated compounds including different drug classes of antibacterials and are affected by a variety of chemically unrelated substances. The mar genes regulate accumulation and thus intracellular concentrations of quinolones by altering the expression of porins and efflux pumps.
Another efflux pump, AcrAB, extrudes quinolones out of the bacteria. The pump is partly controlled by the mar gene and appears to be the major mechanism of resistance for mar mutants. Salicylate and tetracycline induce MarA production, a positive regulator of acrAB transcription, so that salicylate stimulates fluoroquinolone resistance selection.
Additional nontopoisomerase resistance mechanisms that are not under mar control can change quinolone resistance patterns. The nfxB gene codes for an altered outer cell membrane protein F, thereby decreasing quinolone entry into the cell.
In addition, soxRS gene products, which are involved in bacterial adaptation to superoxide stress, affect fluoroquinolone activity, too. Various combinations of target enzyme alteration, diminished antibiotic accumulation, and efflux are often seen in fluoroquinolone-resistant E.
Cross-resistance between fluoroquinolones and antibacterials of chemically unrelated drug classes is associated with the increased expression of efflux pumps because of their limited substrate specificity.
For example, MexAB confers resistance to nonfluorinated and fluoroquinolones, tetracycline, and chloramphenicol, Mex CD confers resistance to fluoroquinolones, erythromycin, trimethoprim, and triclosan, Mex EF confers resistance to the latter plus chloramphenicol, imipenem, and triclosan, and Mex XY confers resistance to fluoroquinolones, erythromycin, and aminoglycosides.
Several comprehensive reviews have summarized the impact of fluoroquinolone-extrusion and resistance.
Consequently, a fluoroquinolone resistant or even multidrug-resistant phenotype can easily be selected by an exposure to a broad range of chemically unrelated drug classes, thus, representing the fourth type of cross-resistance.
These examples illustrate the complexity of fluoroquinolone resistance mechanisms, selection by fluoroquinolones and coselection of resistance by chemically unrelated classes of antibacterials and antiseptics.
Fluoroquinolone Resistance Epidemiology 3. The fluorinated quinolones are characterized by more marked antibacterial activity against uropathogens, so that ciprofloxacin resistant E.
The same holds true for uropathogenic E. Likewise, uropathogens studied between the years 1996 and in the province of British Columbia demonstrated an increase in fluoroquinolone resistance. The resistance rates in E.