The selection of resistance to and the mutagenicity of different fluoroquinolones in Staphylococcus aureus and Streptococcus pneumoniae

Abstract

Two quinolone-susceptible Staphylococcus aureus and five quinolone-susceptible Streptococcus pneumoniae isolates were used to obtain in-vitro quinolone-resistant mutants in a multistep resistance selection process. The fluoroquinolones used were ciprofloxacin, moxifloxacin, levofloxacin, gemifloxacin, trovafloxacin and clinafloxacin. The mutagenicity of these quinolones was determined by the Salmonella and the Escherichia coli retromutation assays. All quinolone-resistant Staph. aureus mutants had at least one mutation in the grlA gene, while 86.6% of quinolone-resistant Strep. pneumoniae mutants had mutations in either or both the gyrA and parC genes. Moxifloxacin and levofloxacin selected resistant mutants later than the other quinolones, but this difference was more obvious in Staph. aureus. Accumulation of the fluoroquinolones by Staph. aureus did not explain these differences, since levofloxacin and moxifloxacin accumulated inside bacteria to the same extent as clinafloxacin and trovafloxacin. The results also showed that moxifloxacin and levofloxacin had less mutagenic potency in both mutagenicity assays, suggesting a possible relationship between the selection of resistance to quinolones and the mutagenic potency of the molecule. Furthermore, gemifloxacin selected efflux mutants more frequently than the other quinolones used. Thus, the risk of developing quinolone resistance may depend on the density of the microorganism at the infection site and the concentration of the fluoroquinolone, and also on the mutagenicity of the quinolone used, with moxifloxacin and levofloxacin being the least mutagenic.

Characterization of New Staphylococcal Cassette Chromosome mec (SCC mec ) and Topoisomerase Genes in Fluoroquinolone- and Methicillin-Resistant Staphylococcus pseudintermedius

“…AB037671) (Fig. 2) but differed from (8,13,14,18,27,30 (1) showed that all methicillin-resistant strains containing SCCmec II-III were clonally related. They belong to ST71, agr type III (Table 1), which is the predominant clonal group in North and Central Europe (1).…”

“…The mechanism of resistance to fluoroquinolones was investigated by sequence analysis of the topoisomerase II (gyrA and gyrB) and IV (grlA and grlB) genes, since mutations in these genes have been shown to confer resistance to fluoroquinolones on Staphylococcus aureus (8,11,13,14,18,27,30). Fragments of gyrA, gyrB, grlA, and grlB of type strains S. pseudintermedius CCUG49543 T (also known as LMG 22219 T [10]) (CCUG, Culture Collection, University of Göteborg, Göteborg, Sweden) and Staphylococcus intermedius DSM20373 T (also known as NCTC 11048 T ) (DSMZ, German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany) were amplified by PCR and sequenced on an ABI Prism 3100 genetic analyzer (Applied Biosystems, Foster City, CA) using oligonucleotide primers (Table 2) designed from conserved regions found after alignment of DNA sequences of grlB/grlA and gyrB/gyrA from S. aureus (GenBank accession no.…”

In Vivo Efficacy of Moxifloxacin Compared with Cloxacillin and Vancomycin in a Staphylococcus aureus Rabbit Arthritis Experimental Model

“…The successful use of ciprofloxacin or ofloxacin alone (13,21,25) or in combination (8) for treatment of S. aureus skeletal infections has been described. Moxifloxacin exhibits enhanced activity against S. aureus (16, 19), has a low propensity to select in vitro and in vivo resistant mutants (1,11,18,21,25), and diffuses well in synovial fluid (SF) (6). One paper has reported the successful use of moxifloxacin in bone and joint infections in the clinical setting (12).…”

Accumulation of 99m Tc-Ciprofloxacin in Staphylococcus aureus and Pseudomonas aeruginosa

“…Resistance to ciprofloxacin is mediated by the alteration of these targets and/or the overexpression of efflux pumps (1,7,9,10). The second mechanism of resistance decreases intracellular concentration of ciprofloxacin.…”

“…Finally, freshly eluted pertechnetate (0.2 to 1.1 GBq) was added, and the resulting solution was vigorously stirred and kept at room temperature for 15 min. Accumulation was performed as described previously and measured at two different end points, 5 and 30 min (4,5,9). Briefly, strains were cultured in Luria-Bertani broth overnight at 37°C.…”