Ozenoxacin: mechanism of action, pharmacokinetic and clinical applications

General Description

Ozenoxacin is a topical antibiotic that inhibits bacterial DNA synthesis, targeting enzymes responsible for replication and organization of bacterial DNA. It shows high inhibitory activity against Gram-positive bacteria like S. aureus and S. pyogenes, with rapid penetration inside the bacterial cell and high intrabacterial concentrations. Ozenoxacin has no or negligible systemic absorption, making it safe for topical use in various skin infections such as impetigo, infected eczema, and dermatitis. It effectively eliminates bacteria causing the infection and reduces inflammation, promoting wound healing. Ozenoxacin is suitable for use in different age groups and exhibits good tolerability and safety profile. Further research is required to explore its full potential and optimal use in different clinical scenarios.

Figure 1. Cream of ozenoxacin

Mechanism of action

Ozenoxacin is a quinolone antibiotic that functions by inhibiting the activity of two enzymes involved in bacterial DNA synthesis, namely DNA gyrase and topoisomerase IV. These enzymes play crucial roles in the replication, transcription, and organization of bacterial DNA. DNA gyrase is responsible for negative supercoiling of DNA, while topoisomerase IV decatenates daughter molecules of DNA after replication. Ozenoxacin has been shown to inhibit both DNA gyrase and topoisomerase IV simultaneously at low concentrations in bacteria such as S. aureus SA113, demonstrating its high inhibitory activity. This may be attributed to its rapid penetration inside the bacterial cell and high intrabacterial concentrations compared to other quinolones. The ability of ozenoxacin to accumulate inside Gram-positive bacterial cells may also reflect its apparent resistance to certain efflux pumps, which affect the activity of other quinolones. In killing curve experiments, ozenoxacin demonstrated higher bactericidal activity against S. aureus and S. pyogenes compared to mupirocin and fusidic acid. These characteristics collectively indicate that ozenoxacin is highly effective against Gram-positive bacteria. ¹

Pharmacokinetic

Ozenoxacin is a topical antibiotic that has been shown in clinical pharmacokinetic studies to exhibit no or negligible systemic absorption following repeated topical application of varying strengths (1% or 2%) of ozenoxacin cream or ointment to intact or abraded skin in healthy adult volunteers and patients with impetigo. Analysis of tape stripping samples and skin punch biopsy samples following topical application of ozenoxacin 2% cream to healthy volunteers showed that ozenoxacin does not penetrate the skin, with concentrations being high in the stratum corneum, low in the epidermis, and below the limit of quantitation in the dermis on most study days. In rare cases, ozenoxacin plasma concentrations above the lower limit of quantification were found in children treated with ozenoxacin 1% cream for impetigo. As systemic absorption of ozenoxacin is minimal, its tissue distribution, metabolism, and elimination in humans have not been investigated. ²

Clinical applications

Ozenoxacin is a topical antibiotic that has shown promising clinical applications in the treatment of various skin infections. With its unique mechanism of action, Ozenoxacin specifically targets and inhibits the growth of bacteria responsible for causing infection. One of the notable clinical applications of Ozenoxacin is in the management of impetigo, a highly contagious bacterial skin infection commonly seen in children. Clinical trials have demonstrated the efficacy of Ozenoxacin in eradicating the causative pathogens, such as Staphylococcus aureus and Streptococcus pyogenes, leading to rapid resolution of symptoms and improvement in the condition. Furthermore, Ozenoxacin has also been evaluated in the treatment of other superficial skin infections, including infected eczema and infected dermatitis. In these conditions, Ozenoxacin has shown favorable outcomes by effectively eliminating the bacteria causing the infection, reducing inflammation, and promoting wound healing. Importantly, Ozenoxacin exhibits good tolerability and safety profile, making it suitable for use in different age groups, including infants and children. Its topical formulation allows for convenient application directly to the affected area, ensuring targeted delivery and optimal therapeutic effect. In conclusion, Ozenoxacin holds great promise as a topical antibiotic for the treatment of various skin infections, providing an effective and safe option for patients of different age groups. Further research and clinical studies are warranted to explore its full potential and determine its optimal use in different clinical scenarios. ³

Reference

1. Fàbrega A, Madurga S, Giralt E, Vila J. Mechanism of action of and resistance to quinolones. Microb Biotechnol. 2009;2:40?61.

2. Gropper S, Cepero AL, Santos B, Kruger D. Systemic bioavailability and safety of twice-daily topical ozenoxacin 1% cream in adults and children with impetigo. Future Microbiol. 2014;9:S33–40.

3. Vila J, Hebert AA, Torrelo A, López Y, Tato M, García-Castillo M, Cantón R. Ozenoxacin: a review of preclinical and clinical efficacy. Expert Rev Anti Infect Ther. 2019;17(3):159-168.