Y López1, M Tato2, D Gargallo-Viola3, R Cantón2, J Vila4, I Zsolt5. 1. Institute of Global Health of Barcelona, Barcelona, Spain. 2. Department of Clinical Microbiology, Hospital Universitario Ramón y Cajal & Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain. 3. ABAC Therapeutics, Barcelona, Spain. 4. Institute of Global Health of Barcelona, Barcelona, Spain; Department of Clinical Microbiology, Hospital Clinic, School of Medicine, University of Barcelona, Spain. Electronic address: jvila@clinic.cat. 5. Medical Department, Ferrer Internacional, Barcelona, Spain.
Abstract
BACKGROUND: To evaluate the activity of ozenoxacin (OZN) in Staphylococcus aureus strains overexpressing the efflux pump-encoding genes mepA and norA. 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 minimum inhibitory concentrations (MICs) of OZN, moxifloxacin (MOX), levofloxacin (LVX), ciprofloxacin (CIP) and norfloxacin (NOR) in the presence and absence of reserpine (20 mg/L) were determined using the microdilution method. RESULTS: The MIC of OZN was lower in all evaluated strains compared with the other studied quinolones and was independent of the pump 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 the presence of reserpine. MIC values for LVX 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 0.833 mg/L and 0.167 to 1 mg/L, respectively). Overproduction of the efflux pump MepA did not affect CIP whereas it increased 8-fold the MIC of NOR. Overproduction of NorA increased ~5-fold and ~40-fold the MICs of CIP and NOR, respectively, resulting in a high-level of resistance to these antibiotics compared with OZN (0.007 mg/L). CONCLUSION: OZN does not seem to be a substrate for the efflux pumps MepA and NorA, which are commonly found in Gram-positive bacteria and that affect other quinolones.
BACKGROUND: To evaluate the activity of ozenoxacin (OZN) in Staphylococcus aureus strains overexpressing the efflux pump-encoding genes mepA and norA. 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 minimum inhibitory concentrations (MICs) of OZN, moxifloxacin (MOX), levofloxacin (LVX), ciprofloxacin (CIP) and norfloxacin (NOR) in the presence and absence of reserpine (20 mg/L) were determined using the microdilution method. RESULTS: The MIC of OZN was lower in all evaluated strains compared with the other studied quinolones and was independent of the pump 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 the presence of reserpine. MIC values for LVX 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 0.833 mg/L and 0.167 to 1 mg/L, respectively). Overproduction of the efflux pump MepA did not affect CIP whereas it increased 8-fold the MIC of NOR. Overproduction of NorA increased ~5-fold and ~40-fold the MICs of CIP and NOR, respectively, resulting in a high-level of resistance to these antibiotics compared with OZN (0.007 mg/L). CONCLUSION:OZN does not seem to be a substrate for the efflux pumps MepA and NorA, which are commonly found in Gram-positive bacteria and that affect other quinolones.