Microbial resistance to antibiotics necessitates the development of alternative treatments to address the challenges posed by severe bacterial infections. Bacteriophages are regaining clinical relevance, but the effectiveness of phage therapy depends directly on the route of administration and the carrier used. This review provides a critical overview of the therapeutic potential of phages, emphasizing different strategies for delivery to the site of infection. We focus on the preclinical and clinical data on phage therapies using various routes of administration, such as oral, intravenous, inhalation, topical, and local administration to joints and bones. In view of different phage formulations, including liquid suspension, phages immobilized in polymers or liposome-based carriers, we highlight the potential challenges and obstacles that may affect phage stability and bioavailability and limit the successful outcome of therapy. This review serves to enhance the understanding of the integration of materials engineering with clinical practice and production standardization, to address these issues. Additionally, a clear knowledge of the bacteriophage and pharmacokinetics of phage preparations is necessary to implement safe and efficacious bacteriophage treatment in the era of antimicrobial resistance.

SUMMARY: Skin and soft tissue infections represent a major clinical challenge. This is particularly true given the rise in antimicrobial resistance, the increasing prevalence of chronic wounds, and the growing number of immunocompromised patients. Conventional antibiotic therapies are frequently compromised by multidrug-resistant pathogens, biofilm formation, and disruption of the skin microbiome, underscoring the urgent need for alternative or adjunctive antibacterial strategies. Bacteriophages, viruses that specifically infect and lyse bacteria, have re-emerged as promising therapeutic agents due to their high specificity, activity against antibiotic-resistant strains, and capacity to target biofilm-associated infections. This review provides a comprehensive overview of current advances in bacteriophage-based approaches for the treatment of cutaneous infections and skin disorders. We discuss the biological principles of phage therapy, its advantages and limitations, and the regulatory and manufacturing challenges associated with clinical translation. Particular emphasis is placed on topical and biomaterial-based phage delivery platforms, including hydrogels, nanocarriers, and adhesive wound dressings, designed to enhance phage stability, local bioavailability, and therapeutic efficacy. Furthermore, we summarize experimental and clinical evidence supporting the use of bacteriophages against the most clinically relevant skin pathogens. By integrating data from in vitro studies, animal models, clinical trials, and compassionate-use cases, this review highlights both the therapeutic potential and current limitations of phage-based interventions in dermatology. Collectively, the available evidence supports the use of bacteriophages as a viable component of future precision antimicrobial therapies for skin infections, while emphasizing the need for well-designed clinical trials, standardized production protocols, and optimized delivery systems to enable broader clinical adoption.