Transfersomal Phage Cocktail Is an Effective Treatment against Methicillin-Resistant Staphylococcus aureus-Mediated Skin and Soft Tissue Infections

Abstract

The emergence of drug resistance has rekindled interest in phage therapy as an alternative treatment option; its potency, safety, and proven efficacy are worth noting. However, phage therapy still suffers from issues of poor stability, narrow spectra, and poor pharmacokinetic profiles. Therefore, it is essential to look into the use of drug delivery systems for efficient delivery of lytic phages The present study evaluated the use of nanostructured lipid-based carriers, i.e., transfersomes, as transdermal delivery systems for encapsulating a methicillin-resistant (MRSA) phage cocktail. Furthermore, the therapeutic potential of the encapsulated phage cocktail in resolving experimental soft tissue infections in rats was studied. Results from stability and phage titer experiments indicated that the transfersome-entrapped phage cocktail showed better persistence and stability than did free phages. Rats treated with the transfersome-entrapped phage cocktail resolved the experimental thigh infections within a period of 7 days, unlike the 20-day period required for untreated animals. The findings of the present study support the use of transfersomes as delivery agents to enhance the stability and persistence of the encapsulated phages. In addition, this study highlights the advantages offered by transfersome-encapsulated phages in providing better therapeutic options than free phages for treating skin and soft tissue infections. The transfersome-entrapped phage cocktail was able to protect all test animals (with no deaths) even when administered with a delay of 12 h postinfection, unlike free phages, thus making this treatment option more suitable for clinical settings.

Characterization of Clinical MRSA Isolates from Northern Spain and Assessment of Their Susceptibility to Phage-Derived Antimicrobials

“…Bacteriophages have already been proven successful for the treatment of MRSA infections affecting skin and soft tissues [41], septicaemia [42] and wounds [43]. Here, we tested the lytic activities of two myophages, phiIPLA-RODI and phiIPLA-C1C, against the 67 MRSA clinical isolates.…”

Applications of Personalised Phage Therapy highlighting the importance of Bacteriophage Banks against Emerging Antimicrobial Resistance

“…The majority of research work has been elaborated for safer delivery and treatment of infections of wounds, burns, lungs, soft tissues, etc. and have targeted pathogenic MRSA, K. pneumoniae and S. pneumoniae majorly in mouse models [78][79][80][81][82] . It is hard to indicate that the guidelines for application and regulation of phage therapy are not established by medical agencies in India for compassionate use/others.…”

Enhancing Whole Phage Therapy and Their Derived Antimicrobial Enzymes through Complex Formulation

“…This competition could, thus, decrease the overall efficacy of the treatment through the faster propagation one of them gets. Indeed, within the published literature, the change in the titer of individual phage components is often not studied and, instead, relies upon the reporting of the total phage content [ 80 , 81 , 82 ]. Competition between phages for bacterial binding sites could also potentially have a deleterious effect on phage activities in cocktails where phages are applied simultaneously (immediate release), in the absence of any other compounds or formulation and, as such, it would be advantageous to select phages which target different bacterial receptors.…”