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.

The emerging global crisis of antibiotic resistance demands new alternative antibacterial solutions. Although bacteriophages have been used to combat bacterial infections for over a century, a dramatic boost in phage studies has recently been observed. In the development of modern phage applications, a scientific rationale is strongly required and newly isolated phages need to be examined in detail. In this study, we present the full characterization of bacteriophages BF9, BF15, and BF17, with lytic activity against extended-spectrum β-lactamases (ESBLs)- and AmpC β-lactamases (AmpC)-producing Escherichia coli, the prevalence of which has increased significantly in livestock in recent decades, representing a great hazard to food safety and a public health risk. Comparative genomic and phylogenetic analysis indicated that BF9, BF15, and BF17 represent the genera Dhillonvirus, Tequatrovirus, and Asteriusvirus, respectively. All three phages significantly reduced in vitro growth of their bacterial host and retained the ability to lyse bacteria after preincubation at wide ranges of temperature (−20–40 °C) and pH (5–9). The results described herein indicate the lytic nature of BF9, BF15, and BF17, which, along with the absence of genes encoding toxins and bacterial virulence factors, represents an undoubted asset in terms of future phage application.

Therapeutic application of bacterial viruses (phage therapy) has in recent years been rediscovered by many scientists, as a method which may potentially replace conventional antibacterial strategies. However, one of the main problems related to phage application is the stability of bacterial viruses. Though many techniques have been used to sustain phage activity, novel tools are needed to allow long-term phage storage and application in versatile forms. In this study, we combined two well-known methods for bacteriophage immobilization. First, encapsulated phages were obtained by means of extrusion–ionic gelation, and then alginate microspheres were dried using the lyophilization process (freeze-drying). To overcome the risk of phage instability upon dehydration, the microspheres were prepared with the addition of 0.3 M mannitol. Bacteriophage-loaded microspheres were stored at room temperature for 30 days and subsequently exposed to simulated gastric fluid (SGF). The survival of encapsulated phages after drying was significantly higher in the presence of mannitol. The highest number of viable bacteriophages exceeding 4.8 log₁₀ pfu/mL in SGF were recovered from encapsulated and freeze-dried microspheres, while phages in lyophilized lysate were completely inactivated. Although the method requires optimization, it may be a promising approach for the immobilization of bacteriophages in terms of practical application.

Bacterial cellulose (BC), an extracellular polysaccharide synthesized by various bacterial strains. It exhibits high tensile strength, water retention, crystallinity, and biocompatibility, making it valuable in biomedical, cosmetic, food, textile, and paper industries. This study examined the effects of six carbon sources on BC production by Komagataeibacter sucrofermentans, identifying fructose as the most effective. A Box–Behnken experimental design was employed to investigate the effects of three variables (fructose concentration, temperature, and cultivation time) on cellulose yield. The optimized cultivation conditions were: fructose concentration of 227.5 g/L, temperature of 28.0 °C, and cultivation time of 295 h, resulting in a BC yield of 63.07 ± 2.91 g/L. Subsequently, BC’s potential as a bacteriophage carrier was assessed. Escherichia coli phage T4 and Staphylococcus aureus phage vB_SauS_CS1 (CS1) were immobilized within BC hydrogels, and their antibacterial activities were assessed through in vitro experiments. These findings suggest BC’s promise as a phage delivery platform for biomedical applications.

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.

Biofilms formed by Candida albicans pose therapeutic challenges due to their resistance to conventional antimicrobials, highlighting the need for more effective treatments. Rhamnolipids (RLs) are biosurfactants with diverse antimicrobial properties. Bacteriophages are viruses that target specific bacterial strains. Recent studies have shown that they may affect biofilm formation by fungi and yeasts. This study investigated the combined antimicrobial effects of RLs and bacteriophages against C. albicans biofilms, focusing on their anti-adhesive and inhibitory effects on biofilm development. RT-PCR assays were used to analyze gene modulation in C. albicans biofilm formation in response to RLs and bacteriophage treatments, while hyphae formation was examined using microscopy. The results showed that RLs-bacteriophage combinations significantly reduced biofilm formation compared to individual treatments. A combination of 200 mg/L RLs with bacteriophage BF9 led to a 94.8% reduction in biofilm formation. In a subsequent model, the same RL concentration with bacteriophage LO5/1f nearly eliminated biofilm formation (~96%). Gene expression analysis revealed downregulation of key biofilm-associated genes when Candida cells were treated with 200 mg/L RLs and four bacteriophages (BF17, LO5/1f, JG004, FD). These results show the potential of RL and bacteriophage combinations in combating C. albicans biofilms, presenting a promising therapeutic approach against resilient infections.