Mutant prevention concentration of ozenoxacin for quinolone-susceptible or -resistant Staphylococcus aureus and Staphylococcus epidermidis

• Published in: PloS one 2019-10, Vol.14 (10), p.e0223326-e0223326
• Main Authors: López, Y, Tato, M, Gargallo-Viola, D, Cantón, R, Vila, J, Zsolt, I
• Format: Article
• Language: English
• Subjects: Aminopyridines - toxicity; Anti-Bacterial Agents - toxicity; Antimicrobial agents; Bacterial diseases; Bacterial infections; Bacterial Proteins - genetics; Biology and life sciences; Ciprofloxacin; Cocci; Deoxyribonucleic acid; Dermatologic agents; Disease susceptibility; DNA; DNA Gyrase - genetics; Drug resistance; Drug Resistance, Bacterial; Drug therapy; E coli; Fluorination; Gene mutation; Genetic aspects; Gram-positive cocci; Hospitals; Infeccions per estafilococs; Infection; Infections; Infectious skin diseases; Laboratories; Levofloxacin; Malalties de la pell; Medicine and health sciences; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Methicillin-Resistant Staphylococcus aureus - genetics; Microbial drug resistance; Mupirocin; Mutants; Mutation; Ozenoxacin; Prevention; Quinolones; Quinolones - toxicity; Retapamulin; Risk factors; Skin; Skin diseases; Staphylococcal infections; Staphylococcus; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus epidermidis - drug effects; Staphylococcus epidermidis - genetics; Staphylococcus infections; Strains (organisms)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0223326

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.