Comparative activity of ozenoxacin and other quinolones in Staphylococcus aureus strains overexpressing the efflux pumps encoding genes mepA and norA.

Abstract Background To evaluate the activity of ozenoxacin (OZN) in Staphylococcus aureus strains with overexpression of mepA and norA genes, which encode efflux pumps. Methods S. aureus NCTC-8325-1, S. aureus NCTC 8225-2 (overexpressing mepA), S. aureus SA 1199 and S. aureus SA 1199B (overexpressing norA) were used. The minimal inhibitory concentration (MIC) of OZN, moxifloxacin (MOX), levofloxacin (LVX), ciprofloxacin (CIP) and norfloxacin (NOR) in the presence/absence of reserpine (20 mg/L) were performed by microdilution method. Results The MIC of OZN was lower in all evaluated strains in comparison with the other studied quinolones and independent of the pump that is being overexpressed. MIC values of OZN ranged from 0.005 to 0.007 mg/L. Similar results were observed with MOX with MIC values between 0.021 and 0.031 mg/L, without variations in presence of reserpine. In the case of LEV, the MIC values were between 0.167 and 1 mg/L with a slight increase in MIC observed in strains overexpressing the mepA or norA genes (from 0.250 to 0.833mg/L and 0.167 to 1 mg/L, respectively). The overproduction of the efflux pump MepA did not affect CIP whereas it increased 8-fold the MIC of NOR. Finally, the overproduction of NorA affects by a ∼ 5-fold and ∼ 40-fold increase the MICs of CIP and NOR, respectively, resulting in a high-level of resistance to these antibiotics in comparison with OZN (0.007 mg/L). Conclusion OZN does not seem to be a substrate for the efflux pumps MepA and NorA, commonly found in Gram-positive bacteria and that affect other quinolones.