Muhammad Muneeb, Asfand Yar Khan, Aftab Shaukat, Yonggang Qu
Multidrug-resistant Staphylococcus aureus, including methicillin-resistant strains (MRSA) pose an increasing risk to animal health and are a known zoonotic risk in the One Health paradigm. The use of bacteriophage cocktails (combinations of two or more lytic phages) have gained interest for expanding host range, inhibiting phage-resistant mutants, and disrupting biofilms, a growing challenge in conventional antibiotic therapy. This review aims to summarise the existing literature on phage cocktails against MDR S. aureus in three different animal populations: pets, livestock and wild animals. For livestock, particularly dairy cattle, a number of cocktails have advanced from in vitro characterization and murine mastitis models to pilot field trials, with one randomized study showing an 81.3 % bacteriological cure rate for naturally occurring S. aureus mastitis. Companion animal research is in the intermediate phase, and polyvalent phages against both S. pseudintermedius and S. aureus have been shown to be effective in canine pyoderma and otitis, with a recent study of a canine fracture-related infection showing efficacy comparable to prolonged antibiotic treatment. However, there are no specific studies on wild animals and this is a gap in knowledge. Some of the ongoing problems are the development of phage resistance, the instability of biological matrices like milk and serum, anti-phage immune responses, and the lack of harmonized regulatory guidelines for veterinary phage products. New technologies such as liposomal encapsulation, hydrogel delivery, and phage-antibiotic synergy are promising. A recent EU approval of a phage feed additive for poultry is a regulatory milestone. Although they show promise, phage cocktails are still in the investigational stages. They have a significant clinical and public health potential that must be confirmed by increasing multicenter field trials in livestock, well-controlled studies in companion animals, systematic investigations of wildlife reservoirs, standardized dosing, extensive safety testing and regulatory harmonization prior to recommending their routine use in veterinary medicine.