JDNPPA Original Research: The Future of Topical Antibiotics in Dermatology

By Kripa Ahuja, MS, and Peter Lio MD

Introduction

Antibiotics have drastically changed the medical landscape since the discovery of penicillin in the early 1920s. In the ensuing years, research into antibiotics flourished. Today,  they are considered critical components of the therapeutic armamentarium and can mean the difference between life and death. The growing threat of antibiotic resistance, however, can make infections harder to treat, biofilms protect bacteria from antibiotics, and allergies can cause adverse reactions rendering certain classes useless. Despite these adversities, ongoing research aims to develop better formulations and alternative treatments to overcome these limitations and preserve the efficacy of antibiotics while better understanding their role in health and disease.

Dermatologic Considerations

Within dermatology, antibiotics play a large role as they offer a multitude of purposes beyond simply treating infections. The skin microbiome—and more specifically, its state of dysbiosis—is implicated in a host of dermatological conditions, including acne, alopecia areata, atopic dermatitis (AD), hidradenitis suppurativa (HS), and psoriasis.^1,2 Further evidence supports a bidirectional interaction between the gut and the skin, with gut microorganisms influencing skin health through their metabolic activities and immunological effects.² This interplay highlights the broader impacts of antibiotics beyond their antibacterial properties. Staphylococcus aureus, a well-known colonizer in AD, produces a serine protease toxin that directly activates peripheral sensory neurons and causes itch.³ While the primary anti-inflammatory mechanism of doxycycline is thought to be via inhibition of metalloproteinases, reducing toxin-producing bacteria may explain some of the anti-inflammatory activity seen with many antibiotics.⁴

Additionally, antibiotics may alter gut physiology to secrete circulating bioactive compounds, further expanding their therapeutic scope beyond antibacterial action. Insights into these mechanisms have refined our understanding of various pathophysiological processes and have catalyzed advancements in targeted therapeutic technologies. For example, dilute bleach baths have shown efficacy in treating AD. Initially, they were thought to work via an antibacterial mechanism, but since then, they have been shown not to possess antimicrobial activity against Staphylococcus aureus when used at the normally recommended concentrations.⁵

Topical therapies abound in dermatology, and antimicrobials are no exception. There are many potential advantages to using topical antibiotics, as well as some disadvantages, outlined in Table 1.

Hypochlorous Acid Hydrogels

Despite the verdict on dilute bleach baths, the active ingredient of bleach, hypochlorous acid, does indeed possess broad antibacterial properties, and stabilized hydrogels with hypochlorous acid have been used both as prescription devices and now, commonly as over-the-counter preparations that also have anti-inflammatory and wound-healing properties.^6,7

Hydrogels are being formulated with antimicrobial activity to facilitate faster recovery, especially for wound healing. ⁸Beyond this, like dilute bleach baths in AD, hypochlorous hydrogels have demonstrated excellent efficacy in reducing itch and inflammation in mouse studies.⁹ Hypochlorous acid hydrogels, postulated to decrease interleukin (IL)-12 production, exhibited a response similar to topical corticosteroid treatments in terms of reducing scratching behavior.⁹Importantly, these hydrogel preparations are not ototoxic, which is a significant limitation of another widely used disinfectant, chlorhexidine. There are suggestions that some version of these hydrogels may one day replace older surgical preparation antimicrobials.⁶

Endolysins

An important limiting factor for topical clindamycin is antibiotic resistance.¹⁰ Innovation has provided new hope against antibacterial resistance with topical endolysins. Endolysins are peptidoglycan hydrolases encoded by bacteriophages, the viruses that can attack specific bacteria, bringing the adage “the enemy of my enemy is my friend” to life.

Endolysins have demonstrated success against a wide range of bacteria, including multidrug-resistant strains.¹¹ Due to structural differences between gram-positive and gram-negative bacteria, endolysins are being targeted with protein engineering and formulation techniques to improve stability in the hopes of better treating gram-negative bacteria.¹¹

While many novel antimicrobial approaches have been attempted, studies have demonstrated no added benefit from the use of antibacterial therapeutic clothing in improving AD, including symptoms, quality of life, topical corticosteroid use, skin flora, or healthcare costs.¹² Botanical agents, however, have opened up some new potential pathways. Clinical trials have recently demonstrated that zabalafin, a novel topical antibiotic agent derived from a botanical source, has achieved therapeutic success in treating AD in early clinical trials.^13,14 This agent, like other botanicals, may also possess anti-inflammatory and antipruritic properties in addition to the antibacterial aspects.

Conclusion

Topical antibiotics have evolved into successful agents with relatively few drawbacks.^15–17 Factors that have contributed to topical antibiotic success in dermatology include targeted delivery of a high concentration of a drug to the site of infection, small amounts of drugs used, lower potential for systemic adverse effects, no disruption of intestinal microbial flora, ease of application for pediatric patients, and cost-effectiveness.^15–17 On the other hand, some potential limitations to topical antibiotics include certain agents being associated with contact dermatitis, a minimal depth of penetration, possible impairments in wound healing, the possibility of contamination after storage in patients’ homes, the potential for systemic absorption and toxicity if applied over a larger area, and potential difficulty of application for particular anatomic sites.^15–17 It should be noted that application site pain from topical antibiotics is more often attributed to the vehicle in the topical preparation rather than the antibiotic itself. However, this can also be a potential negative.¹⁷

In summary, topical antibiotics can be used for a variety of purposes in dermatology, including burn infections, wound healing, skin infections, acne, and more.^15,18 Future directions may involve nanotechnologies, other new delivery approaches, and totally new approaches to manipulating the microbiome as a whole.¹⁹

Table 1. Advantages and Disadvantages of Topical Antibiotics

References

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About the authors

Kripa Ahuja, MS, is a medical student at  Eastern Virginia Medical School in Norfolk, VA. Disclosures: None

Peter A. Lio, MD, is a Clinical Assistant Professor of Dermatology and Pediatrics at Northwestern University Feinberg School of Medicine and a partner at Medical Dermatology Associates of Chicago. Disclosures: Dr. Lio reports being on the speaker’s bureau for AbbVie, Arcutis, Eli Lilly, Galderma, Hyphens Pharma, Incyte, La Roche-Posay/L’Oreal, Pfizer, Pierre-Fabre Dermatologie, Regeneron/Sanofi Genzyme, Verrica; reports consulting/advisory boards for Alphyn Biologics (stock options), AbbVie, Almirall, Amyris, Arcutis, ASLAN, Bristol-Myers Squibb, Burt’s Bees, Castle Biosciences, Codex Labs (stock options), Concerto Biosci (stock options), Dermavant, Eli Lilly, Galderma, Janssen, LEO Pharma, Lipidor, L’Oreal, Merck, Micreos, MyOR Diagnostics, Regeneron/Sanofi Genzyme, Sibel Health, Skinfix, Suneco Technologies (stock options), Theraplex, UCB, Unilever, Verdant Scientific (stock options), Verrica, Yobee Care (stock options). In addition, Dr. Lio has a patent pending for a Theraplex product with royalties paid and is a Board member and Scientific Advisory Committee Member emeritus of the National Eczema Association.