Accumulation of four quinolones by Serratia marcescens was measured fluorometrically. The passage of quinolones through the outer membrane was studied in both lipopolysaccharide-deficient and porin-deficient mutants. The lipopolysaccharide (LPS) layer formed a partially effective barrier for highly hydrophobic quinolones such as nalidixic acid. Quinolones with a low relative hydrophobicity coefficient seemed to pass preferentially through the water-filled Omp3 porin channels. Results were confirmed when Omp3 was cloned in a porin-defective Escherichia coli.

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.

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The protective effect of ozone may be explained by upregulation of the antioxidant defence system and beneficial effects on blood circulation and in oxygen metabolism. Ozone treatment may represent a therapeutic approach for minimising renal damage after transplantation.