Background Staphylococcus aureus remains the predominant pathogen in diabetic foot infections and prevalence of methicillin resistant S.aureus (MRSA) strains further complicates the situation. The incidence of MRSA in infected foot ulcers is 15–30% and there is an alarming trend for its increase in many countries. Diabetes acts as an immunosuppressive state decreasing the overall immune functioning of body and to worsen the situation, wounds inflicted with drug resistant strains represent a morbid combination in diabetic patients. Foot infections caused by MRSA are associated with an increased risk of amputations, increased hospital stay, increased expenses and higher infection-related mortality. Hence, newer, safer and effective treatment strategies are required for treating MRSA mediated diabetic foot infections. The present study focuses on the use of lytic bacteriophage in combination with linezolid as an effective treatment strategy against foot infection in diabetic population.MethodologyAcute hindpaw infection with S.aureus ATCC 43300 was established in alloxan induced diabetic BALB/c mice. Therapeutic efficacy of a well characterized broad host range lytic bacteriophage, MR-10 was evaluated alone as well as in combination with linezolid in resolving the course of hindpaw foot infection in diabetic mice. The process of wound healing was also investigated.Results and ConclusionsA single administration of phage exhibited efficacy similar to linezolid in resolving the course of hindpaw infection in diabetic animals. However, combination therapy using both the agents was much more effective in arresting the entire infection process (bacterial load, lesion score, foot myeloperoxidase activity and histopathological analysis). The entire process of tissue healing was also hastened. Use of combined agents has been known to decrease the frequency of emergence of resistant mutants, hence this approach can serve as an effective strategy in treating MRSA mediated foot infections in diabetic individuals who do not respond to conventional antibiotic therapy.
Phage therapy presents an alternative therapeutic option in treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA) strains not responding to antibiotic therapy. However, it is essential to study the role of external factors that may influence the yield and potency of phage preparations intended for use in various in vitro and in vivo studies. The present study focuses on the effects of calcium in the entire infection process of a broad-spectrum lytic bacteriophage: MR-10. The presence of calcium increased the adsorption rate of the phage and also participated in the process of penetration of the phage genome into the host cytoplasm. A final concentration of 5 mM of calcium ions supplemented in soft agar during the phage titration process significantly increased the phage titer. Hence, incorporation of such divalent cations during the isolation of lytic phages active against MRSA strains and during the preparation of high-titer active phage preparations would definitely increase the isolation frequency and the final phage yield. This will contribute towards more effective phage preparations for use in treatments against MRSA infections.
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