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Mutant prevention concentration of ozenoxacin for quinolone-susceptible or -resistant Staphylococcus aureus and
Y López1, M Tato2, D Gargallo-Viola3
1Institute of Global Health of Barcelona, Barcelona, Spain.
Abstract:
Ozenoxacin (OZN) belongs to a new generation of non-fluorinated quinolones for the topical treatment of skin infections which has shown to be effective in the treatment of susceptible and resistant Gram-positive cocci. The mutant prevention concentration (MPC) of ozenoxacin, levofloxacin and ciprofloxacin was determined in quinolone-susceptible and -resistant strains including methicillin-susceptible S. aureus, methicillin-resistant S. aureus, methicillin-susceptible S. epidermidis and methicillin-resistant S. epidermidis with different profile of mutation in the quinolone resistance determining regions (QRDR). The MPC value of OZN for the methicillin-susceptible S. aureus strain susceptible to quinolones, without mutations in QRDR, was 0.05 mg/L, being 280-fold lower than that observed with ciprofloxacin and levofloxacin. In methicillin-susceptible and-resistant S. aureus strains with mutations in the gyrA or/and grlA genes the MPC of OZN went from 0.1 to 6 mg/L, whereas the MPC of levofloxacin and ciprofloxacin was > 50 mg/L for the same strains. For methicillin-susceptible and-resistant S. epidermidis the results were similar to those abovementioned for S. aureus. According to our results, the MPC of OZN was far below the quantity of ozenoxacin achieved in the epidermal layer, suggesting that the in vivo selection of mutants, if it occurs, will take place at low frequency. Ozenoxacin is an excellent candidate for the treatment of bacterial infections caused by susceptible and quinolone-resistant staphylococci isolated usually from skin infections.
Insights
Ozenoxacin effectively treats skin infections caused by susceptible and resistant Staphylococcus strains. Its mutant prevention concentration (MPC) is significantly lower than other quinolones, suggesting reduced risk of resistance development.
Area of Science:
- Microbiology
- Dermatology
- Pharmacology
Background:
- Ozenoxacin (OZN) is a novel, non-fluorinated topical quinolone antibiotic.
- It demonstrates efficacy against Gram-positive cocci, including resistant strains.
- Skin infections caused by Staphylococcus species are a significant clinical concern.
Purpose of the Study:
- To determine the mutant prevention concentration (MPC) of ozenoxacin compared to levofloxacin and ciprofloxacin.
- To evaluate OZN's activity against quinolone-susceptible and -resistant Staphylococcus strains.
- To assess the potential for in vivo resistance selection with ozenoxacin treatment.
Main Methods:
- Determination of MPC values for ozenoxacin, levofloxacin, and ciprofloxacin.
- Testing against methicillin-susceptible and -resistant strains of S. aureus and S. epidermidis.
- Analysis of mutations in quinolone resistance-determining regions (QRDR).
Main Results:
- Ozenoxacin exhibited significantly lower MPC values compared to levofloxacin and ciprofloxacin across all tested strains.
- MPC values for OZN were notably lower in strains with QRDR mutations.
- Ozenoxacin's MPC was below the concentrations achieved in epidermal tissue, indicating low potential for resistance selection.
Conclusions:
- Ozenoxacin demonstrates potent activity against susceptible and resistant staphylococcal strains relevant to skin infections.
- Its low MPC suggests a reduced likelihood of resistance development in clinical settings.
- Ozenoxacin is a promising therapeutic option for treating staphylococcal skin infections.
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